A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.
Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA)...
Ausführliche Beschreibung
Autor*in: |
Sofer, Tamar [verfasserIn] |
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E-Artikel |
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Englisch |
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2023 |
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Anmerkung: |
© The Author(s) 2023 |
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Übergeordnetes Werk: |
Enthalten in: Alzheimer's research & therapy - London : BioMed Central, 2009, 15(2023), 1 vom: 30. Aug. |
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Übergeordnetes Werk: |
volume:15 ; year:2023 ; number:1 ; day:30 ; month:08 |
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DOI / URN: |
10.1186/s13195-023-01298-3 |
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SPR052929957 |
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245 | 1 | 2 | |a A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. |
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520 | |a Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. | ||
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700 | 1 | |a Lamar, Melissa |4 aut | |
700 | 1 | |a Wassertheil-Smoller, Sylvia |4 aut | |
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700 | 1 | |a DeCarli, Charles S. |4 aut | |
700 | 1 | |a Gonzalez, Hector M. |4 aut | |
700 | 1 | |a Fornage, Myriam |4 aut | |
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10.1186/s13195-023-01298-3 doi (DE-627)SPR052929957 (SPR)s13195-023-01298-3-e DE-627 ger DE-627 rakwb eng Sofer, Tamar verfasserin aut A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. Admixture (dpeaa)DE-He213 Diverse populations (dpeaa)DE-He213 Polygenic risk score (dpeaa)DE-He213 Mild cognitive impairment (dpeaa)DE-He213 Cognitive decline (dpeaa)DE-He213 Kurniansyah, Nuzulul aut Granot-Hershkovitz, Einat aut Goodman, Matthew O. aut Tarraf, Wassim aut Broce, Iris aut Lipton, Richard B. aut Daviglus, Martha aut Lamar, Melissa aut Wassertheil-Smoller, Sylvia aut Cai, Jianwen aut DeCarli, Charles S. aut Gonzalez, Hector M. aut Fornage, Myriam aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 15(2023), 1 vom: 30. Aug. (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:15 year:2023 number:1 day:30 month:08 https://dx.doi.org/10.1186/s13195-023-01298-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 30 08 |
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10.1186/s13195-023-01298-3 doi (DE-627)SPR052929957 (SPR)s13195-023-01298-3-e DE-627 ger DE-627 rakwb eng Sofer, Tamar verfasserin aut A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. Admixture (dpeaa)DE-He213 Diverse populations (dpeaa)DE-He213 Polygenic risk score (dpeaa)DE-He213 Mild cognitive impairment (dpeaa)DE-He213 Cognitive decline (dpeaa)DE-He213 Kurniansyah, Nuzulul aut Granot-Hershkovitz, Einat aut Goodman, Matthew O. aut Tarraf, Wassim aut Broce, Iris aut Lipton, Richard B. aut Daviglus, Martha aut Lamar, Melissa aut Wassertheil-Smoller, Sylvia aut Cai, Jianwen aut DeCarli, Charles S. aut Gonzalez, Hector M. aut Fornage, Myriam aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 15(2023), 1 vom: 30. Aug. (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:15 year:2023 number:1 day:30 month:08 https://dx.doi.org/10.1186/s13195-023-01298-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 30 08 |
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10.1186/s13195-023-01298-3 doi (DE-627)SPR052929957 (SPR)s13195-023-01298-3-e DE-627 ger DE-627 rakwb eng Sofer, Tamar verfasserin aut A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. Admixture (dpeaa)DE-He213 Diverse populations (dpeaa)DE-He213 Polygenic risk score (dpeaa)DE-He213 Mild cognitive impairment (dpeaa)DE-He213 Cognitive decline (dpeaa)DE-He213 Kurniansyah, Nuzulul aut Granot-Hershkovitz, Einat aut Goodman, Matthew O. aut Tarraf, Wassim aut Broce, Iris aut Lipton, Richard B. aut Daviglus, Martha aut Lamar, Melissa aut Wassertheil-Smoller, Sylvia aut Cai, Jianwen aut DeCarli, Charles S. aut Gonzalez, Hector M. aut Fornage, Myriam aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 15(2023), 1 vom: 30. Aug. (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:15 year:2023 number:1 day:30 month:08 https://dx.doi.org/10.1186/s13195-023-01298-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 30 08 |
allfieldsGer |
10.1186/s13195-023-01298-3 doi (DE-627)SPR052929957 (SPR)s13195-023-01298-3-e DE-627 ger DE-627 rakwb eng Sofer, Tamar verfasserin aut A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. Admixture (dpeaa)DE-He213 Diverse populations (dpeaa)DE-He213 Polygenic risk score (dpeaa)DE-He213 Mild cognitive impairment (dpeaa)DE-He213 Cognitive decline (dpeaa)DE-He213 Kurniansyah, Nuzulul aut Granot-Hershkovitz, Einat aut Goodman, Matthew O. aut Tarraf, Wassim aut Broce, Iris aut Lipton, Richard B. aut Daviglus, Martha aut Lamar, Melissa aut Wassertheil-Smoller, Sylvia aut Cai, Jianwen aut DeCarli, Charles S. aut Gonzalez, Hector M. aut Fornage, Myriam aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 15(2023), 1 vom: 30. Aug. (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:15 year:2023 number:1 day:30 month:08 https://dx.doi.org/10.1186/s13195-023-01298-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 30 08 |
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10.1186/s13195-023-01298-3 doi (DE-627)SPR052929957 (SPR)s13195-023-01298-3-e DE-627 ger DE-627 rakwb eng Sofer, Tamar verfasserin aut A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. Admixture (dpeaa)DE-He213 Diverse populations (dpeaa)DE-He213 Polygenic risk score (dpeaa)DE-He213 Mild cognitive impairment (dpeaa)DE-He213 Cognitive decline (dpeaa)DE-He213 Kurniansyah, Nuzulul aut Granot-Hershkovitz, Einat aut Goodman, Matthew O. aut Tarraf, Wassim aut Broce, Iris aut Lipton, Richard B. aut Daviglus, Martha aut Lamar, Melissa aut Wassertheil-Smoller, Sylvia aut Cai, Jianwen aut DeCarli, Charles S. aut Gonzalez, Hector M. aut Fornage, Myriam aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 15(2023), 1 vom: 30. Aug. (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:15 year:2023 number:1 day:30 month:08 https://dx.doi.org/10.1186/s13195-023-01298-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 30 08 |
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A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. Admixture (dpeaa)DE-He213 Diverse populations (dpeaa)DE-He213 Polygenic risk score (dpeaa)DE-He213 Mild cognitive impairment (dpeaa)DE-He213 Cognitive decline (dpeaa)DE-He213 |
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polygenic risk score for alzheimer’s disease constructed using apoe-region variants has stronger association than apoe alleles with mild cognitive impairment in hispanic/latino adults in the u.s. |
title_auth |
A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. |
abstract |
Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. © The Author(s) 2023 |
abstractGer |
Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. © The Author(s) 2023 |
abstract_unstemmed |
Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. © The Author(s) 2023 |
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title_short |
A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. |
url |
https://dx.doi.org/10.1186/s13195-023-01298-3 |
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author2 |
Kurniansyah, Nuzulul Granot-Hershkovitz, Einat Goodman, Matthew O. Tarraf, Wassim Broce, Iris Lipton, Richard B. Daviglus, Martha Lamar, Melissa Wassertheil-Smoller, Sylvia Cai, Jianwen DeCarli, Charles S. Gonzalez, Hector M. Fornage, Myriam |
author2Str |
Kurniansyah, Nuzulul Granot-Hershkovitz, Einat Goodman, Matthew O. Tarraf, Wassim Broce, Iris Lipton, Richard B. Daviglus, Martha Lamar, Melissa Wassertheil-Smoller, Sylvia Cai, Jianwen DeCarli, Charles S. Gonzalez, Hector M. Fornage, Myriam |
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doi_str |
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up_date |
2024-07-03T15:49:58.566Z |
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