Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus
Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of e...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Oei, Ling [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2014transfer abstract |
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| Umfang: |
8 |
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| Übergeordnetes Werk: |
Enthalten in: Preparation and properties of multi-functional Fe3O4PNIPAM-AAMAu composites - 2013transfer abstract, cell molecular biology, pathophysiology, treatment : official journal of the International Bone and Mineral Society, Amsterdam [u.a.] |
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| Übergeordnetes Werk: |
volume:59 ; year:2014 ; pages:20-27 ; extent:8 |
| Links: |
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| DOI / URN: |
10.1016/j.bone.2013.10.015 |
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| Katalog-ID: |
ELV028125878 |
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| 245 | 1 | 0 | |a Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus |
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| 520 | |a Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. | ||
| 520 | |a Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. | ||
| 700 | 1 | |a Estrada, Karol |4 oth | |
| 700 | 1 | |a Duncan, Emma L. |4 oth | |
| 700 | 1 | |a Christiansen, Claus |4 oth | |
| 700 | 1 | |a Liu, Ching-Ti |4 oth | |
| 700 | 1 | |a Langdahl, Bente L. |4 oth | |
| 700 | 1 | |a Obermayer-Pietsch, Barbara |4 oth | |
| 700 | 1 | |a Riancho, José A. |4 oth | |
| 700 | 1 | |a Prince, Richard L. |4 oth | |
| 700 | 1 | |a van Schoor, Natasja M. |4 oth | |
| 700 | 1 | |a McCloskey, Eugene |4 oth | |
| 700 | 1 | |a Hsu, Yi-Hsiang |4 oth | |
| 700 | 1 | |a Evangelou, Evangelos |4 oth | |
| 700 | 1 | |a Ntzani, Evangelia |4 oth | |
| 700 | 1 | |a Evans, David M. |4 oth | |
| 700 | 1 | |a Alonso, Nerea |4 oth | |
| 700 | 1 | |a Husted, Lise B. |4 oth | |
| 700 | 1 | |a Valero, Carmen |4 oth | |
| 700 | 1 | |a Hernandez, Jose L. |4 oth | |
| 700 | 1 | |a Lewis, Joshua R. |4 oth | |
| 700 | 1 | |a Kaptoge, Stephen K. |4 oth | |
| 700 | 1 | |a Zhu, Kun |4 oth | |
| 700 | 1 | |a Cupples, L. Adrienne |4 oth | |
| 700 | 1 | |a Medina-Gómez, Carolina |4 oth | |
| 700 | 1 | |a Vandenput, Liesbeth |4 oth | |
| 700 | 1 | |a Kim, Ghi Su |4 oth | |
| 700 | 1 | |a Lee, Seung Hun |4 oth | |
| 700 | 1 | |a Castaño-Betancourt, Martha C. |4 oth | |
| 700 | 1 | |a Oei, Edwin H.G. |4 oth | |
| 700 | 1 | |a Martinez, Josefina |4 oth | |
| 700 | 1 | |a Daroszewska, Anna |4 oth | |
| 700 | 1 | |a van der Klift, Marjolein |4 oth | |
| 700 | 1 | |a Mellström, Dan |4 oth | |
| 700 | 1 | |a Herrera, Lizbeth |4 oth | |
| 700 | 1 | |a Karlsson, Magnus K. |4 oth | |
| 700 | 1 | |a Hofman, Albert |4 oth | |
| 700 | 1 | |a Ljunggren, Östen |4 oth | |
| 700 | 1 | |a Pols, Huibert A.P. |4 oth | |
| 700 | 1 | |a Stolk, Lisette |4 oth | |
| 700 | 1 | |a van Meurs, Joyce B.J. |4 oth | |
| 700 | 1 | |a Ioannidis, John P.A. |4 oth | |
| 700 | 1 | |a Zillikens, M. Carola |4 oth | |
| 700 | 1 | |a Lips, Paul |4 oth | |
| 700 | 1 | |a Karasik, David |4 oth | |
| 700 | 1 | |a Uitterlinden, André G. |4 oth | |
| 700 | 1 | |a Styrkarsdottir, Unnur |4 oth | |
| 700 | 1 | |a Brown, Matthew A. |4 oth | |
| 700 | 1 | |a Koh, Jung-Min |4 oth | |
| 700 | 1 | |a Richards, J. Brent |4 oth | |
| 700 | 1 | |a Reeve, Jonathan |4 oth | |
| 700 | 1 | |a Ohlsson, Claes |4 oth | |
| 700 | 1 | |a Ralston, Stuart H. |4 oth | |
| 700 | 1 | |a Kiel, Douglas P. |4 oth | |
| 700 | 1 | |a Rivadeneira, Fernando |4 oth | |
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10.1016/j.bone.2013.10.015 doi GBVA2014011000023.pica (DE-627)ELV028125878 (ELSEVIER)S8756-3282(13)00425-0 DE-627 ger DE-627 rakwb eng 610 610 DE-600 530 VZ 600 VZ 670 VZ 630 580 VZ BIODIV DE-30 fid 48.00 bkl Oei, Ling verfasserin aut Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus 2014transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. Estrada, Karol oth Duncan, Emma L. oth Christiansen, Claus oth Liu, Ching-Ti oth Langdahl, Bente L. oth Obermayer-Pietsch, Barbara oth Riancho, José A. oth Prince, Richard L. oth van Schoor, Natasja M. oth McCloskey, Eugene oth Hsu, Yi-Hsiang oth Evangelou, Evangelos oth Ntzani, Evangelia oth Evans, David M. oth Alonso, Nerea oth Husted, Lise B. oth Valero, Carmen oth Hernandez, Jose L. oth Lewis, Joshua R. oth Kaptoge, Stephen K. oth Zhu, Kun oth Cupples, L. Adrienne oth Medina-Gómez, Carolina oth Vandenput, Liesbeth oth Kim, Ghi Su oth Lee, Seung Hun oth Castaño-Betancourt, Martha C. oth Oei, Edwin H.G. oth Martinez, Josefina oth Daroszewska, Anna oth van der Klift, Marjolein oth Mellström, Dan oth Herrera, Lizbeth oth Karlsson, Magnus K. oth Hofman, Albert oth Ljunggren, Östen oth Pols, Huibert A.P. oth Stolk, Lisette oth van Meurs, Joyce B.J. oth Ioannidis, John P.A. oth Zillikens, M. Carola oth Lips, Paul oth Karasik, David oth Uitterlinden, André G. oth Styrkarsdottir, Unnur oth Brown, Matthew A. oth Koh, Jung-Min oth Richards, J. Brent oth Reeve, Jonathan oth Ohlsson, Claes oth Ralston, Stuart H. oth Kiel, Douglas P. oth Rivadeneira, Fernando oth Enthalten in Elsevier Science Preparation and properties of multi-functional Fe3O4PNIPAM-AAMAu composites 2013transfer abstract cell molecular biology, pathophysiology, treatment : official journal of the International Bone and Mineral Society Amsterdam [u.a.] (DE-627)ELV011494476 volume:59 year:2014 pages:20-27 extent:8 https://doi.org/10.1016/j.bone.2013.10.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 59 2014 20-27 8 045F 610 |
| spelling |
10.1016/j.bone.2013.10.015 doi GBVA2014011000023.pica (DE-627)ELV028125878 (ELSEVIER)S8756-3282(13)00425-0 DE-627 ger DE-627 rakwb eng 610 610 DE-600 530 VZ 600 VZ 670 VZ 630 580 VZ BIODIV DE-30 fid 48.00 bkl Oei, Ling verfasserin aut Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus 2014transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. Estrada, Karol oth Duncan, Emma L. oth Christiansen, Claus oth Liu, Ching-Ti oth Langdahl, Bente L. oth Obermayer-Pietsch, Barbara oth Riancho, José A. oth Prince, Richard L. oth van Schoor, Natasja M. oth McCloskey, Eugene oth Hsu, Yi-Hsiang oth Evangelou, Evangelos oth Ntzani, Evangelia oth Evans, David M. oth Alonso, Nerea oth Husted, Lise B. oth Valero, Carmen oth Hernandez, Jose L. oth Lewis, Joshua R. oth Kaptoge, Stephen K. oth Zhu, Kun oth Cupples, L. Adrienne oth Medina-Gómez, Carolina oth Vandenput, Liesbeth oth Kim, Ghi Su oth Lee, Seung Hun oth Castaño-Betancourt, Martha C. oth Oei, Edwin H.G. oth Martinez, Josefina oth Daroszewska, Anna oth van der Klift, Marjolein oth Mellström, Dan oth Herrera, Lizbeth oth Karlsson, Magnus K. oth Hofman, Albert oth Ljunggren, Östen oth Pols, Huibert A.P. oth Stolk, Lisette oth van Meurs, Joyce B.J. oth Ioannidis, John P.A. oth Zillikens, M. Carola oth Lips, Paul oth Karasik, David oth Uitterlinden, André G. oth Styrkarsdottir, Unnur oth Brown, Matthew A. oth Koh, Jung-Min oth Richards, J. Brent oth Reeve, Jonathan oth Ohlsson, Claes oth Ralston, Stuart H. oth Kiel, Douglas P. oth Rivadeneira, Fernando oth Enthalten in Elsevier Science Preparation and properties of multi-functional Fe3O4PNIPAM-AAMAu composites 2013transfer abstract cell molecular biology, pathophysiology, treatment : official journal of the International Bone and Mineral Society Amsterdam [u.a.] (DE-627)ELV011494476 volume:59 year:2014 pages:20-27 extent:8 https://doi.org/10.1016/j.bone.2013.10.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 59 2014 20-27 8 045F 610 |
| allfields_unstemmed |
10.1016/j.bone.2013.10.015 doi GBVA2014011000023.pica (DE-627)ELV028125878 (ELSEVIER)S8756-3282(13)00425-0 DE-627 ger DE-627 rakwb eng 610 610 DE-600 530 VZ 600 VZ 670 VZ 630 580 VZ BIODIV DE-30 fid 48.00 bkl Oei, Ling verfasserin aut Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus 2014transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. Estrada, Karol oth Duncan, Emma L. oth Christiansen, Claus oth Liu, Ching-Ti oth Langdahl, Bente L. oth Obermayer-Pietsch, Barbara oth Riancho, José A. oth Prince, Richard L. oth van Schoor, Natasja M. oth McCloskey, Eugene oth Hsu, Yi-Hsiang oth Evangelou, Evangelos oth Ntzani, Evangelia oth Evans, David M. oth Alonso, Nerea oth Husted, Lise B. oth Valero, Carmen oth Hernandez, Jose L. oth Lewis, Joshua R. oth Kaptoge, Stephen K. oth Zhu, Kun oth Cupples, L. Adrienne oth Medina-Gómez, Carolina oth Vandenput, Liesbeth oth Kim, Ghi Su oth Lee, Seung Hun oth Castaño-Betancourt, Martha C. oth Oei, Edwin H.G. oth Martinez, Josefina oth Daroszewska, Anna oth van der Klift, Marjolein oth Mellström, Dan oth Herrera, Lizbeth oth Karlsson, Magnus K. oth Hofman, Albert oth Ljunggren, Östen oth Pols, Huibert A.P. oth Stolk, Lisette oth van Meurs, Joyce B.J. oth Ioannidis, John P.A. oth Zillikens, M. Carola oth Lips, Paul oth Karasik, David oth Uitterlinden, André G. oth Styrkarsdottir, Unnur oth Brown, Matthew A. oth Koh, Jung-Min oth Richards, J. Brent oth Reeve, Jonathan oth Ohlsson, Claes oth Ralston, Stuart H. oth Kiel, Douglas P. oth Rivadeneira, Fernando oth Enthalten in Elsevier Science Preparation and properties of multi-functional Fe3O4PNIPAM-AAMAu composites 2013transfer abstract cell molecular biology, pathophysiology, treatment : official journal of the International Bone and Mineral Society Amsterdam [u.a.] (DE-627)ELV011494476 volume:59 year:2014 pages:20-27 extent:8 https://doi.org/10.1016/j.bone.2013.10.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 59 2014 20-27 8 045F 610 |
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10.1016/j.bone.2013.10.015 doi GBVA2014011000023.pica (DE-627)ELV028125878 (ELSEVIER)S8756-3282(13)00425-0 DE-627 ger DE-627 rakwb eng 610 610 DE-600 530 VZ 600 VZ 670 VZ 630 580 VZ BIODIV DE-30 fid 48.00 bkl Oei, Ling verfasserin aut Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus 2014transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. Estrada, Karol oth Duncan, Emma L. oth Christiansen, Claus oth Liu, Ching-Ti oth Langdahl, Bente L. oth Obermayer-Pietsch, Barbara oth Riancho, José A. oth Prince, Richard L. oth van Schoor, Natasja M. oth McCloskey, Eugene oth Hsu, Yi-Hsiang oth Evangelou, Evangelos oth Ntzani, Evangelia oth Evans, David M. oth Alonso, Nerea oth Husted, Lise B. oth Valero, Carmen oth Hernandez, Jose L. oth Lewis, Joshua R. oth Kaptoge, Stephen K. oth Zhu, Kun oth Cupples, L. Adrienne oth Medina-Gómez, Carolina oth Vandenput, Liesbeth oth Kim, Ghi Su oth Lee, Seung Hun oth Castaño-Betancourt, Martha C. oth Oei, Edwin H.G. oth Martinez, Josefina oth Daroszewska, Anna oth van der Klift, Marjolein oth Mellström, Dan oth Herrera, Lizbeth oth Karlsson, Magnus K. oth Hofman, Albert oth Ljunggren, Östen oth Pols, Huibert A.P. oth Stolk, Lisette oth van Meurs, Joyce B.J. oth Ioannidis, John P.A. oth Zillikens, M. Carola oth Lips, Paul oth Karasik, David oth Uitterlinden, André G. oth Styrkarsdottir, Unnur oth Brown, Matthew A. oth Koh, Jung-Min oth Richards, J. Brent oth Reeve, Jonathan oth Ohlsson, Claes oth Ralston, Stuart H. oth Kiel, Douglas P. oth Rivadeneira, Fernando oth Enthalten in Elsevier Science Preparation and properties of multi-functional Fe3O4PNIPAM-AAMAu composites 2013transfer abstract cell molecular biology, pathophysiology, treatment : official journal of the International Bone and Mineral Society Amsterdam [u.a.] (DE-627)ELV011494476 volume:59 year:2014 pages:20-27 extent:8 https://doi.org/10.1016/j.bone.2013.10.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 59 2014 20-27 8 045F 610 |
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10.1016/j.bone.2013.10.015 doi GBVA2014011000023.pica (DE-627)ELV028125878 (ELSEVIER)S8756-3282(13)00425-0 DE-627 ger DE-627 rakwb eng 610 610 DE-600 530 VZ 600 VZ 670 VZ 630 580 VZ BIODIV DE-30 fid 48.00 bkl Oei, Ling verfasserin aut Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus 2014transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. Estrada, Karol oth Duncan, Emma L. oth Christiansen, Claus oth Liu, Ching-Ti oth Langdahl, Bente L. oth Obermayer-Pietsch, Barbara oth Riancho, José A. oth Prince, Richard L. oth van Schoor, Natasja M. oth McCloskey, Eugene oth Hsu, Yi-Hsiang oth Evangelou, Evangelos oth Ntzani, Evangelia oth Evans, David M. oth Alonso, Nerea oth Husted, Lise B. oth Valero, Carmen oth Hernandez, Jose L. oth Lewis, Joshua R. oth Kaptoge, Stephen K. oth Zhu, Kun oth Cupples, L. Adrienne oth Medina-Gómez, Carolina oth Vandenput, Liesbeth oth Kim, Ghi Su oth Lee, Seung Hun oth Castaño-Betancourt, Martha C. oth Oei, Edwin H.G. oth Martinez, Josefina oth Daroszewska, Anna oth van der Klift, Marjolein oth Mellström, Dan oth Herrera, Lizbeth oth Karlsson, Magnus K. oth Hofman, Albert oth Ljunggren, Östen oth Pols, Huibert A.P. oth Stolk, Lisette oth van Meurs, Joyce B.J. oth Ioannidis, John P.A. oth Zillikens, M. Carola oth Lips, Paul oth Karasik, David oth Uitterlinden, André G. oth Styrkarsdottir, Unnur oth Brown, Matthew A. oth Koh, Jung-Min oth Richards, J. Brent oth Reeve, Jonathan oth Ohlsson, Claes oth Ralston, Stuart H. oth Kiel, Douglas P. oth Rivadeneira, Fernando oth Enthalten in Elsevier Science Preparation and properties of multi-functional Fe3O4PNIPAM-AAMAu composites 2013transfer abstract cell molecular biology, pathophysiology, treatment : official journal of the International Bone and Mineral Society Amsterdam [u.a.] (DE-627)ELV011494476 volume:59 year:2014 pages:20-27 extent:8 https://doi.org/10.1016/j.bone.2013.10.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 59 2014 20-27 8 045F 610 |
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Oei, Ling @@aut@@ Estrada, Karol @@oth@@ Duncan, Emma L. @@oth@@ Christiansen, Claus @@oth@@ Liu, Ching-Ti @@oth@@ Langdahl, Bente L. @@oth@@ Obermayer-Pietsch, Barbara @@oth@@ Riancho, José A. @@oth@@ Prince, Richard L. @@oth@@ van Schoor, Natasja M. @@oth@@ McCloskey, Eugene @@oth@@ Hsu, Yi-Hsiang @@oth@@ Evangelou, Evangelos @@oth@@ Ntzani, Evangelia @@oth@@ Evans, David M. @@oth@@ Alonso, Nerea @@oth@@ Husted, Lise B. @@oth@@ Valero, Carmen @@oth@@ Hernandez, Jose L. @@oth@@ Lewis, Joshua R. @@oth@@ Kaptoge, Stephen K. @@oth@@ Zhu, Kun @@oth@@ Cupples, L. Adrienne @@oth@@ Medina-Gómez, Carolina @@oth@@ Vandenput, Liesbeth @@oth@@ Kim, Ghi Su @@oth@@ Lee, Seung Hun @@oth@@ Castaño-Betancourt, Martha C. @@oth@@ Oei, Edwin H.G. @@oth@@ Martinez, Josefina @@oth@@ Daroszewska, Anna @@oth@@ van der Klift, Marjolein @@oth@@ Mellström, Dan @@oth@@ Herrera, Lizbeth @@oth@@ Karlsson, Magnus K. @@oth@@ Hofman, Albert @@oth@@ Ljunggren, Östen @@oth@@ Pols, Huibert A.P. @@oth@@ Stolk, Lisette @@oth@@ van Meurs, Joyce B.J. @@oth@@ Ioannidis, John P.A. @@oth@@ Zillikens, M. Carola @@oth@@ Lips, Paul @@oth@@ Karasik, David @@oth@@ Uitterlinden, André G. @@oth@@ Styrkarsdottir, Unnur @@oth@@ Brown, Matthew A. @@oth@@ Koh, Jung-Min @@oth@@ Richards, J. Brent @@oth@@ Reeve, Jonathan @@oth@@ Ohlsson, Claes @@oth@@ Ralston, Stuart H. @@oth@@ Kiel, Douglas P. @@oth@@ Rivadeneira, Fernando @@oth@@ |
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The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. 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Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus |
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Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. |
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Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. |
| abstract_unstemmed |
Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV028125878</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230625153102.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">180603s2014 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.bone.2013.10.015</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBVA2014011000023.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV028125878</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S8756-3282(13)00425-0</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2=" "><subfield code="a">610</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">DE-600</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">530</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">600</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">670</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">630</subfield><subfield code="a">580</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">BIODIV</subfield><subfield code="q">DE-30</subfield><subfield code="2">fid</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">48.00</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Oei, Ling</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2014transfer abstract</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">8</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p <5×10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p =4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p =0.17), displaying high degree of heterogeneity (I2 =57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p =0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Estrada, Karol</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Duncan, Emma L.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Christiansen, Claus</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Liu, Ching-Ti</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Langdahl, Bente L.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Obermayer-Pietsch, Barbara</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Riancho, José A.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Prince, Richard L.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">van Schoor, Natasja M.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">McCloskey, Eugene</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hsu, Yi-Hsiang</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Evangelou, Evangelos</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ntzani, Evangelia</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Evans, David M.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Alonso, Nerea</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Husted, Lise B.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Valero, Carmen</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hernandez, Jose L.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Lewis, Joshua R.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kaptoge, Stephen K.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhu, Kun</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Cupples, L. 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