Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility
Abstract Cigarette smoking is the major environmental risk factor for chronic obstructive pulmonary disease (COPD). Genome-wide association studies have provided compelling associations for three loci with COPD. In this study, we aimed to estimate direct, i.e., independent from smoking, and indirect...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Siedlinski, Mateusz [verfasserIn] Tingley, Dustin [verfasserIn] Lipman, Peter J. [verfasserIn] Cho, Michael H. [verfasserIn] Litonjua, Augusto A. [verfasserIn] Sparrow, David [verfasserIn] Bakke, Per [verfasserIn] Gulsvik, Amund [verfasserIn] Lomas, David A. [verfasserIn] Anderson, Wayne [verfasserIn] Kong, Xiangyang [verfasserIn] Rennard, Stephen I. [verfasserIn] Beaty, Terri H. [verfasserIn] Hokanson, John E. [verfasserIn] Crapo, James D. [verfasserIn] Lange, Christoph [verfasserIn] Silverman, Edwin K. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2013 |
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| Schlagwörter: |
Chronic Obstructive Pulmonary Disease |
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| Übergeordnetes Werk: |
Enthalten in: Human genetics |
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| Übergeordnetes Werk: |
volume:132 ; year:2013 ; number:4 ; day:09 ; month:01 ; pages:431-441 |
| Links: |
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| DOI / URN: |
10.1007/s00439-012-1262-3 |
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SPR006361226 |
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| 245 | 1 | 0 | |a Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility |
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| 520 | |a Abstract Cigarette smoking is the major environmental risk factor for chronic obstructive pulmonary disease (COPD). Genome-wide association studies have provided compelling associations for three loci with COPD. In this study, we aimed to estimate direct, i.e., independent from smoking, and indirect effects of those loci on COPD development using mediation analysis. We included a total of 3,424 COPD cases and 1,872 unaffected controls with data on two smoking-related phenotypes: lifetime average smoking intensity and cumulative exposure to tobacco smoke (pack years). Our analysis revealed that effects of two linked variants (rs1051730 and rs8034191) in the AGPHD1/CHRNA3 cluster on COPD development are significantly, yet not entirely, mediated by the smoking-related phenotypes. Approximately 30 % of the total effect of variants in the AGPHD1/CHRNA3 cluster on COPD development was mediated by pack years. Simultaneous analysis of modestly (r2 = 0.21) linked markers in CHRNA3 and IREB2 revealed that an even larger (~42 %) proportion of the total effect of the CHRNA3 locus on COPD was mediated by pack years after adjustment for an IREB2 single nucleotide polymorphism. This study confirms the existence of direct effects of the AGPHD1/CHRNA3, IREB2, FAM13A and HHIP loci on COPD development. While the association of the AGPHD1/CHRNA3 locus with COPD is significantly mediated by smoking-related phenotypes, IREB2 appears to affect COPD independently of smoking. | ||
| 650 | 4 | |a Chronic Obstructive Pulmonary Disease |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Mediation Analysis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Smoking Intensity |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Chronic Obstructive Pulmonary Disease Subject |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Chronic Obstructive Pulmonary Disease Case |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Tingley, Dustin |e verfasserin |4 aut | |
| 700 | 1 | |a Lipman, Peter J. |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Michael H. |e verfasserin |4 aut | |
| 700 | 1 | |a Litonjua, Augusto A. |e verfasserin |4 aut | |
| 700 | 1 | |a Sparrow, David |e verfasserin |4 aut | |
| 700 | 1 | |a Bakke, Per |e verfasserin |4 aut | |
| 700 | 1 | |a Gulsvik, Amund |e verfasserin |4 aut | |
| 700 | 1 | |a Lomas, David A. |e verfasserin |4 aut | |
| 700 | 1 | |a Anderson, Wayne |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Xiangyang |e verfasserin |4 aut | |
| 700 | 1 | |a Rennard, Stephen I. |e verfasserin |4 aut | |
| 700 | 1 | |a Beaty, Terri H. |e verfasserin |4 aut | |
| 700 | 1 | |a Hokanson, John E. |e verfasserin |4 aut | |
| 700 | 1 | |a Crapo, James D. |e verfasserin |4 aut | |
| 700 | 1 | |a Lange, Christoph |e verfasserin |4 aut | |
| 700 | 1 | |a Silverman, Edwin K. |e verfasserin |4 aut | |
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10.1007/s00439-012-1262-3 doi (DE-627)SPR006361226 (SPR)s00439-012-1262-3-e DE-627 ger DE-627 rakwb eng 610 ASE 44.48 bkl Siedlinski, Mateusz verfasserin aut Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cigarette smoking is the major environmental risk factor for chronic obstructive pulmonary disease (COPD). Genome-wide association studies have provided compelling associations for three loci with COPD. In this study, we aimed to estimate direct, i.e., independent from smoking, and indirect effects of those loci on COPD development using mediation analysis. We included a total of 3,424 COPD cases and 1,872 unaffected controls with data on two smoking-related phenotypes: lifetime average smoking intensity and cumulative exposure to tobacco smoke (pack years). Our analysis revealed that effects of two linked variants (rs1051730 and rs8034191) in the AGPHD1/CHRNA3 cluster on COPD development are significantly, yet not entirely, mediated by the smoking-related phenotypes. Approximately 30 % of the total effect of variants in the AGPHD1/CHRNA3 cluster on COPD development was mediated by pack years. Simultaneous analysis of modestly (r2 = 0.21) linked markers in CHRNA3 and IREB2 revealed that an even larger (~42 %) proportion of the total effect of the CHRNA3 locus on COPD was mediated by pack years after adjustment for an IREB2 single nucleotide polymorphism. This study confirms the existence of direct effects of the AGPHD1/CHRNA3, IREB2, FAM13A and HHIP loci on COPD development. While the association of the AGPHD1/CHRNA3 locus with COPD is significantly mediated by smoking-related phenotypes, IREB2 appears to affect COPD independently of smoking. Chronic Obstructive Pulmonary Disease (dpeaa)DE-He213 Mediation Analysis (dpeaa)DE-He213 Smoking Intensity (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Subject (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Case (dpeaa)DE-He213 Tingley, Dustin verfasserin aut Lipman, Peter J. verfasserin aut Cho, Michael H. verfasserin aut Litonjua, Augusto A. verfasserin aut Sparrow, David verfasserin aut Bakke, Per verfasserin aut Gulsvik, Amund verfasserin aut Lomas, David A. verfasserin aut Anderson, Wayne verfasserin aut Kong, Xiangyang verfasserin aut Rennard, Stephen I. verfasserin aut Beaty, Terri H. verfasserin aut Hokanson, John E. verfasserin aut Crapo, James D. verfasserin aut Lange, Christoph verfasserin aut Silverman, Edwin K. verfasserin aut Enthalten in Human genetics <Berlin> Berlin : Springer, 1964 132(2013), 4 vom: 09. Jan., Seite 431-441 (DE-627)253723973 (DE-600)1459188-1 1432-1203 nnns volume:132 year:2013 number:4 day:09 month:01 pages:431-441 https://dx.doi.org/10.1007/s00439-012-1262-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.48 ASE AR 132 2013 4 09 01 431-441 |
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10.1007/s00439-012-1262-3 doi (DE-627)SPR006361226 (SPR)s00439-012-1262-3-e DE-627 ger DE-627 rakwb eng 610 ASE 44.48 bkl Siedlinski, Mateusz verfasserin aut Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cigarette smoking is the major environmental risk factor for chronic obstructive pulmonary disease (COPD). Genome-wide association studies have provided compelling associations for three loci with COPD. In this study, we aimed to estimate direct, i.e., independent from smoking, and indirect effects of those loci on COPD development using mediation analysis. We included a total of 3,424 COPD cases and 1,872 unaffected controls with data on two smoking-related phenotypes: lifetime average smoking intensity and cumulative exposure to tobacco smoke (pack years). Our analysis revealed that effects of two linked variants (rs1051730 and rs8034191) in the AGPHD1/CHRNA3 cluster on COPD development are significantly, yet not entirely, mediated by the smoking-related phenotypes. Approximately 30 % of the total effect of variants in the AGPHD1/CHRNA3 cluster on COPD development was mediated by pack years. Simultaneous analysis of modestly (r2 = 0.21) linked markers in CHRNA3 and IREB2 revealed that an even larger (~42 %) proportion of the total effect of the CHRNA3 locus on COPD was mediated by pack years after adjustment for an IREB2 single nucleotide polymorphism. This study confirms the existence of direct effects of the AGPHD1/CHRNA3, IREB2, FAM13A and HHIP loci on COPD development. While the association of the AGPHD1/CHRNA3 locus with COPD is significantly mediated by smoking-related phenotypes, IREB2 appears to affect COPD independently of smoking. Chronic Obstructive Pulmonary Disease (dpeaa)DE-He213 Mediation Analysis (dpeaa)DE-He213 Smoking Intensity (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Subject (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Case (dpeaa)DE-He213 Tingley, Dustin verfasserin aut Lipman, Peter J. verfasserin aut Cho, Michael H. verfasserin aut Litonjua, Augusto A. verfasserin aut Sparrow, David verfasserin aut Bakke, Per verfasserin aut Gulsvik, Amund verfasserin aut Lomas, David A. verfasserin aut Anderson, Wayne verfasserin aut Kong, Xiangyang verfasserin aut Rennard, Stephen I. verfasserin aut Beaty, Terri H. verfasserin aut Hokanson, John E. verfasserin aut Crapo, James D. verfasserin aut Lange, Christoph verfasserin aut Silverman, Edwin K. verfasserin aut Enthalten in Human genetics <Berlin> Berlin : Springer, 1964 132(2013), 4 vom: 09. Jan., Seite 431-441 (DE-627)253723973 (DE-600)1459188-1 1432-1203 nnns volume:132 year:2013 number:4 day:09 month:01 pages:431-441 https://dx.doi.org/10.1007/s00439-012-1262-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.48 ASE AR 132 2013 4 09 01 431-441 |
| allfields_unstemmed |
10.1007/s00439-012-1262-3 doi (DE-627)SPR006361226 (SPR)s00439-012-1262-3-e DE-627 ger DE-627 rakwb eng 610 ASE 44.48 bkl Siedlinski, Mateusz verfasserin aut Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cigarette smoking is the major environmental risk factor for chronic obstructive pulmonary disease (COPD). Genome-wide association studies have provided compelling associations for three loci with COPD. In this study, we aimed to estimate direct, i.e., independent from smoking, and indirect effects of those loci on COPD development using mediation analysis. We included a total of 3,424 COPD cases and 1,872 unaffected controls with data on two smoking-related phenotypes: lifetime average smoking intensity and cumulative exposure to tobacco smoke (pack years). Our analysis revealed that effects of two linked variants (rs1051730 and rs8034191) in the AGPHD1/CHRNA3 cluster on COPD development are significantly, yet not entirely, mediated by the smoking-related phenotypes. Approximately 30 % of the total effect of variants in the AGPHD1/CHRNA3 cluster on COPD development was mediated by pack years. Simultaneous analysis of modestly (r2 = 0.21) linked markers in CHRNA3 and IREB2 revealed that an even larger (~42 %) proportion of the total effect of the CHRNA3 locus on COPD was mediated by pack years after adjustment for an IREB2 single nucleotide polymorphism. This study confirms the existence of direct effects of the AGPHD1/CHRNA3, IREB2, FAM13A and HHIP loci on COPD development. While the association of the AGPHD1/CHRNA3 locus with COPD is significantly mediated by smoking-related phenotypes, IREB2 appears to affect COPD independently of smoking. Chronic Obstructive Pulmonary Disease (dpeaa)DE-He213 Mediation Analysis (dpeaa)DE-He213 Smoking Intensity (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Subject (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Case (dpeaa)DE-He213 Tingley, Dustin verfasserin aut Lipman, Peter J. verfasserin aut Cho, Michael H. verfasserin aut Litonjua, Augusto A. verfasserin aut Sparrow, David verfasserin aut Bakke, Per verfasserin aut Gulsvik, Amund verfasserin aut Lomas, David A. verfasserin aut Anderson, Wayne verfasserin aut Kong, Xiangyang verfasserin aut Rennard, Stephen I. verfasserin aut Beaty, Terri H. verfasserin aut Hokanson, John E. verfasserin aut Crapo, James D. verfasserin aut Lange, Christoph verfasserin aut Silverman, Edwin K. verfasserin aut Enthalten in Human genetics <Berlin> Berlin : Springer, 1964 132(2013), 4 vom: 09. Jan., Seite 431-441 (DE-627)253723973 (DE-600)1459188-1 1432-1203 nnns volume:132 year:2013 number:4 day:09 month:01 pages:431-441 https://dx.doi.org/10.1007/s00439-012-1262-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.48 ASE AR 132 2013 4 09 01 431-441 |
| allfieldsGer |
10.1007/s00439-012-1262-3 doi (DE-627)SPR006361226 (SPR)s00439-012-1262-3-e DE-627 ger DE-627 rakwb eng 610 ASE 44.48 bkl Siedlinski, Mateusz verfasserin aut Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cigarette smoking is the major environmental risk factor for chronic obstructive pulmonary disease (COPD). Genome-wide association studies have provided compelling associations for three loci with COPD. In this study, we aimed to estimate direct, i.e., independent from smoking, and indirect effects of those loci on COPD development using mediation analysis. We included a total of 3,424 COPD cases and 1,872 unaffected controls with data on two smoking-related phenotypes: lifetime average smoking intensity and cumulative exposure to tobacco smoke (pack years). Our analysis revealed that effects of two linked variants (rs1051730 and rs8034191) in the AGPHD1/CHRNA3 cluster on COPD development are significantly, yet not entirely, mediated by the smoking-related phenotypes. Approximately 30 % of the total effect of variants in the AGPHD1/CHRNA3 cluster on COPD development was mediated by pack years. Simultaneous analysis of modestly (r2 = 0.21) linked markers in CHRNA3 and IREB2 revealed that an even larger (~42 %) proportion of the total effect of the CHRNA3 locus on COPD was mediated by pack years after adjustment for an IREB2 single nucleotide polymorphism. This study confirms the existence of direct effects of the AGPHD1/CHRNA3, IREB2, FAM13A and HHIP loci on COPD development. While the association of the AGPHD1/CHRNA3 locus with COPD is significantly mediated by smoking-related phenotypes, IREB2 appears to affect COPD independently of smoking. Chronic Obstructive Pulmonary Disease (dpeaa)DE-He213 Mediation Analysis (dpeaa)DE-He213 Smoking Intensity (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Subject (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Case (dpeaa)DE-He213 Tingley, Dustin verfasserin aut Lipman, Peter J. verfasserin aut Cho, Michael H. verfasserin aut Litonjua, Augusto A. verfasserin aut Sparrow, David verfasserin aut Bakke, Per verfasserin aut Gulsvik, Amund verfasserin aut Lomas, David A. verfasserin aut Anderson, Wayne verfasserin aut Kong, Xiangyang verfasserin aut Rennard, Stephen I. verfasserin aut Beaty, Terri H. verfasserin aut Hokanson, John E. verfasserin aut Crapo, James D. verfasserin aut Lange, Christoph verfasserin aut Silverman, Edwin K. verfasserin aut Enthalten in Human genetics <Berlin> Berlin : Springer, 1964 132(2013), 4 vom: 09. Jan., Seite 431-441 (DE-627)253723973 (DE-600)1459188-1 1432-1203 nnns volume:132 year:2013 number:4 day:09 month:01 pages:431-441 https://dx.doi.org/10.1007/s00439-012-1262-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.48 ASE AR 132 2013 4 09 01 431-441 |
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10.1007/s00439-012-1262-3 doi (DE-627)SPR006361226 (SPR)s00439-012-1262-3-e DE-627 ger DE-627 rakwb eng 610 ASE 44.48 bkl Siedlinski, Mateusz verfasserin aut Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cigarette smoking is the major environmental risk factor for chronic obstructive pulmonary disease (COPD). Genome-wide association studies have provided compelling associations for three loci with COPD. In this study, we aimed to estimate direct, i.e., independent from smoking, and indirect effects of those loci on COPD development using mediation analysis. We included a total of 3,424 COPD cases and 1,872 unaffected controls with data on two smoking-related phenotypes: lifetime average smoking intensity and cumulative exposure to tobacco smoke (pack years). Our analysis revealed that effects of two linked variants (rs1051730 and rs8034191) in the AGPHD1/CHRNA3 cluster on COPD development are significantly, yet not entirely, mediated by the smoking-related phenotypes. Approximately 30 % of the total effect of variants in the AGPHD1/CHRNA3 cluster on COPD development was mediated by pack years. Simultaneous analysis of modestly (r2 = 0.21) linked markers in CHRNA3 and IREB2 revealed that an even larger (~42 %) proportion of the total effect of the CHRNA3 locus on COPD was mediated by pack years after adjustment for an IREB2 single nucleotide polymorphism. This study confirms the existence of direct effects of the AGPHD1/CHRNA3, IREB2, FAM13A and HHIP loci on COPD development. While the association of the AGPHD1/CHRNA3 locus with COPD is significantly mediated by smoking-related phenotypes, IREB2 appears to affect COPD independently of smoking. Chronic Obstructive Pulmonary Disease (dpeaa)DE-He213 Mediation Analysis (dpeaa)DE-He213 Smoking Intensity (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Subject (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Case (dpeaa)DE-He213 Tingley, Dustin verfasserin aut Lipman, Peter J. verfasserin aut Cho, Michael H. verfasserin aut Litonjua, Augusto A. verfasserin aut Sparrow, David verfasserin aut Bakke, Per verfasserin aut Gulsvik, Amund verfasserin aut Lomas, David A. verfasserin aut Anderson, Wayne verfasserin aut Kong, Xiangyang verfasserin aut Rennard, Stephen I. verfasserin aut Beaty, Terri H. verfasserin aut Hokanson, John E. verfasserin aut Crapo, James D. verfasserin aut Lange, Christoph verfasserin aut Silverman, Edwin K. verfasserin aut Enthalten in Human genetics <Berlin> Berlin : Springer, 1964 132(2013), 4 vom: 09. Jan., Seite 431-441 (DE-627)253723973 (DE-600)1459188-1 1432-1203 nnns volume:132 year:2013 number:4 day:09 month:01 pages:431-441 https://dx.doi.org/10.1007/s00439-012-1262-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.48 ASE AR 132 2013 4 09 01 431-441 |
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Enthalten in Human genetics <Berlin> 132(2013), 4 vom: 09. Jan., Seite 431-441 volume:132 year:2013 number:4 day:09 month:01 pages:431-441 |
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Siedlinski, Mateusz @@aut@@ Tingley, Dustin @@aut@@ Lipman, Peter J. @@aut@@ Cho, Michael H. @@aut@@ Litonjua, Augusto A. @@aut@@ Sparrow, David @@aut@@ Bakke, Per @@aut@@ Gulsvik, Amund @@aut@@ Lomas, David A. @@aut@@ Anderson, Wayne @@aut@@ Kong, Xiangyang @@aut@@ Rennard, Stephen I. @@aut@@ Beaty, Terri H. @@aut@@ Hokanson, John E. @@aut@@ Crapo, James D. @@aut@@ Lange, Christoph @@aut@@ Silverman, Edwin K. @@aut@@ |
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Siedlinski, Mateusz |
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Siedlinski, Mateusz ddc 610 bkl 44.48 misc Chronic Obstructive Pulmonary Disease misc Mediation Analysis misc Smoking Intensity misc Chronic Obstructive Pulmonary Disease Subject misc Chronic Obstructive Pulmonary Disease Case Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility |
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610 ASE 44.48 bkl Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility Chronic Obstructive Pulmonary Disease (dpeaa)DE-He213 Mediation Analysis (dpeaa)DE-He213 Smoking Intensity (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Subject (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Case (dpeaa)DE-He213 |
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Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility |
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Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility |
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Siedlinski, Mateusz Tingley, Dustin Lipman, Peter J. Cho, Michael H. Litonjua, Augusto A. Sparrow, David Bakke, Per Gulsvik, Amund Lomas, David A. Anderson, Wayne Kong, Xiangyang Rennard, Stephen I. Beaty, Terri H. Hokanson, John E. Crapo, James D. Lange, Christoph Silverman, Edwin K. |
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dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (copd) susceptibility |
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Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility |
| abstract |
Abstract Cigarette smoking is the major environmental risk factor for chronic obstructive pulmonary disease (COPD). Genome-wide association studies have provided compelling associations for three loci with COPD. In this study, we aimed to estimate direct, i.e., independent from smoking, and indirect effects of those loci on COPD development using mediation analysis. We included a total of 3,424 COPD cases and 1,872 unaffected controls with data on two smoking-related phenotypes: lifetime average smoking intensity and cumulative exposure to tobacco smoke (pack years). Our analysis revealed that effects of two linked variants (rs1051730 and rs8034191) in the AGPHD1/CHRNA3 cluster on COPD development are significantly, yet not entirely, mediated by the smoking-related phenotypes. Approximately 30 % of the total effect of variants in the AGPHD1/CHRNA3 cluster on COPD development was mediated by pack years. Simultaneous analysis of modestly (r2 = 0.21) linked markers in CHRNA3 and IREB2 revealed that an even larger (~42 %) proportion of the total effect of the CHRNA3 locus on COPD was mediated by pack years after adjustment for an IREB2 single nucleotide polymorphism. This study confirms the existence of direct effects of the AGPHD1/CHRNA3, IREB2, FAM13A and HHIP loci on COPD development. While the association of the AGPHD1/CHRNA3 locus with COPD is significantly mediated by smoking-related phenotypes, IREB2 appears to affect COPD independently of smoking. |
| abstractGer |
Abstract Cigarette smoking is the major environmental risk factor for chronic obstructive pulmonary disease (COPD). Genome-wide association studies have provided compelling associations for three loci with COPD. In this study, we aimed to estimate direct, i.e., independent from smoking, and indirect effects of those loci on COPD development using mediation analysis. We included a total of 3,424 COPD cases and 1,872 unaffected controls with data on two smoking-related phenotypes: lifetime average smoking intensity and cumulative exposure to tobacco smoke (pack years). Our analysis revealed that effects of two linked variants (rs1051730 and rs8034191) in the AGPHD1/CHRNA3 cluster on COPD development are significantly, yet not entirely, mediated by the smoking-related phenotypes. Approximately 30 % of the total effect of variants in the AGPHD1/CHRNA3 cluster on COPD development was mediated by pack years. Simultaneous analysis of modestly (r2 = 0.21) linked markers in CHRNA3 and IREB2 revealed that an even larger (~42 %) proportion of the total effect of the CHRNA3 locus on COPD was mediated by pack years after adjustment for an IREB2 single nucleotide polymorphism. This study confirms the existence of direct effects of the AGPHD1/CHRNA3, IREB2, FAM13A and HHIP loci on COPD development. While the association of the AGPHD1/CHRNA3 locus with COPD is significantly mediated by smoking-related phenotypes, IREB2 appears to affect COPD independently of smoking. |
| abstract_unstemmed |
Abstract Cigarette smoking is the major environmental risk factor for chronic obstructive pulmonary disease (COPD). Genome-wide association studies have provided compelling associations for three loci with COPD. In this study, we aimed to estimate direct, i.e., independent from smoking, and indirect effects of those loci on COPD development using mediation analysis. We included a total of 3,424 COPD cases and 1,872 unaffected controls with data on two smoking-related phenotypes: lifetime average smoking intensity and cumulative exposure to tobacco smoke (pack years). Our analysis revealed that effects of two linked variants (rs1051730 and rs8034191) in the AGPHD1/CHRNA3 cluster on COPD development are significantly, yet not entirely, mediated by the smoking-related phenotypes. Approximately 30 % of the total effect of variants in the AGPHD1/CHRNA3 cluster on COPD development was mediated by pack years. Simultaneous analysis of modestly (r2 = 0.21) linked markers in CHRNA3 and IREB2 revealed that an even larger (~42 %) proportion of the total effect of the CHRNA3 locus on COPD was mediated by pack years after adjustment for an IREB2 single nucleotide polymorphism. This study confirms the existence of direct effects of the AGPHD1/CHRNA3, IREB2, FAM13A and HHIP loci on COPD development. While the association of the AGPHD1/CHRNA3 locus with COPD is significantly mediated by smoking-related phenotypes, IREB2 appears to affect COPD independently of smoking. |
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Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility |
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Tingley, Dustin Lipman, Peter J. Cho, Michael H. Litonjua, Augusto A. Sparrow, David Bakke, Per Gulsvik, Amund Lomas, David A. Anderson, Wayne Kong, Xiangyang Rennard, Stephen I. Beaty, Terri H. Hokanson, John E. Crapo, James D. Lange, Christoph Silverman, Edwin K. |
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Tingley, Dustin Lipman, Peter J. Cho, Michael H. Litonjua, Augusto A. Sparrow, David Bakke, Per Gulsvik, Amund Lomas, David A. Anderson, Wayne Kong, Xiangyang Rennard, Stephen I. Beaty, Terri H. Hokanson, John E. Crapo, James D. Lange, Christoph Silverman, Edwin K. |
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10.1007/s00439-012-1262-3 |
| up_date |
2024-07-03T22:34:19.930Z |
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| score |
7.400403 |