Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context

Summary: Background: Genome-wide association studies (GWAS) for obstructive sleep apnoea (OSA) are limited due to the underdiagnosis of OSA, leading to misclassification of OSA, which consequently reduces statistical power. We performed a GWAS of OSA in the Million Veteran Program (MVP) of the U.S....
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Autor*in:	Tamar Sofer [verfasserIn] Nuzulul Kurniansyah [verfasserIn] Michael Murray [verfasserIn] Yuk-Lam Ho [verfasserIn] Erik Abner [verfasserIn] Tõnu Esko [verfasserIn] Jennifer E. Huffman [verfasserIn] Kelly Cho [verfasserIn] Peter W.F. Wilson [verfasserIn] Daniel J. Gottlieb [verfasserIn] Andres Metspalu [verfasserIn] Lili Milani [verfasserIn] Reedik Mägi [verfasserIn] Mari Nelis [verfasserIn] Georgi Hudjashov [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Obstructive sleep apnoea Electronic health records Genome-wide association study Sex differences

Übergeordnetes Werk:	In: EBioMedicine - Elsevier, 2015, 90(2023), Seite 104536-
Übergeordnetes Werk:	volume:90 ; year:2023 ; pages:104536-

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.ebiom.2023.104536

Katalog-ID:	DOAJ087475642

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520			\|a Summary: Background: Genome-wide association studies (GWAS) for obstructive sleep apnoea (OSA) are limited due to the underdiagnosis of OSA, leading to misclassification of OSA, which consequently reduces statistical power. We performed a GWAS of OSA in the Million Veteran Program (MVP) of the U.S. Department of Veterans Affairs (VA) healthcare system, where OSA prevalence is close to its true population prevalence. Methods: We performed GWAS of 568,576 MVP participants, stratified by biological sex and by harmonized race/ethnicity and genetic ancestry (HARE) groups of White, Black, Hispanic, and Asian individuals. We considered both BMI adjusted (BMI-adj) and unadjusted (BMI-unadj) models. We replicated associations in independent datasets, and analysed the heterogeneity of OSA genetic associations across HARE and sex groups. We finally performed a larger meta-analysis GWAS of MVP, FinnGen, and the MGB Biobank, totalling 916,696 individuals. Findings: MVP participants are 91% male. OSA prevalence is 21%. In MVP there were 18 and 6 genome-wide significant loci in BMI-unadj and BMI-adj analyses, respectively, corresponding to 21 association regions. Of these, 17 were not previously reported in association with OSA, and 13 replicated in FinnGen (False Discovery Rate p-value < 0.05). There were widespread significant differences in genetic effects between men and women, but less so across HARE groups. Meta-analysis of MVP, FinnGen, and MGB biobank revealed 17 additional, previously unreported, genome-wide significant regions. Interpretation: Sex differences in genetic associations with OSA are widespread, likely associated with multiple OSA risk factors. OSA shares genetic underpinnings with several sleep phenotypes, suggesting shared aetiology and causal pathways. Funding: Described in acknowledgements.
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allfields	10.1016/j.ebiom.2023.104536 doi (DE-627)DOAJ087475642 (DE-599)DOAJc68f8d375fea4798817834dfee36df35 DE-627 ger DE-627 rakwb eng R5-920 Tamar Sofer verfasserin aut Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Background: Genome-wide association studies (GWAS) for obstructive sleep apnoea (OSA) are limited due to the underdiagnosis of OSA, leading to misclassification of OSA, which consequently reduces statistical power. We performed a GWAS of OSA in the Million Veteran Program (MVP) of the U.S. Department of Veterans Affairs (VA) healthcare system, where OSA prevalence is close to its true population prevalence. Methods: We performed GWAS of 568,576 MVP participants, stratified by biological sex and by harmonized race/ethnicity and genetic ancestry (HARE) groups of White, Black, Hispanic, and Asian individuals. We considered both BMI adjusted (BMI-adj) and unadjusted (BMI-unadj) models. We replicated associations in independent datasets, and analysed the heterogeneity of OSA genetic associations across HARE and sex groups. We finally performed a larger meta-analysis GWAS of MVP, FinnGen, and the MGB Biobank, totalling 916,696 individuals. Findings: MVP participants are 91% male. OSA prevalence is 21%. In MVP there were 18 and 6 genome-wide significant loci in BMI-unadj and BMI-adj analyses, respectively, corresponding to 21 association regions. Of these, 17 were not previously reported in association with OSA, and 13 replicated in FinnGen (False Discovery Rate p-value < 0.05). There were widespread significant differences in genetic effects between men and women, but less so across HARE groups. Meta-analysis of MVP, FinnGen, and MGB biobank revealed 17 additional, previously unreported, genome-wide significant regions. Interpretation: Sex differences in genetic associations with OSA are widespread, likely associated with multiple OSA risk factors. OSA shares genetic underpinnings with several sleep phenotypes, suggesting shared aetiology and causal pathways. Funding: Described in acknowledgements. Obstructive sleep apnoea Electronic health records Genome-wide association study Sex differences Medicine R Medicine (General) Nuzulul Kurniansyah verfasserin aut Michael Murray verfasserin aut Yuk-Lam Ho verfasserin aut Erik Abner verfasserin aut Tõnu Esko verfasserin aut Jennifer E. Huffman verfasserin aut Kelly Cho verfasserin aut Peter W.F. Wilson verfasserin aut Daniel J. Gottlieb verfasserin aut Andres Metspalu verfasserin aut Lili Milani verfasserin aut Tõnu Esko verfasserin aut Reedik Mägi verfasserin aut Mari Nelis verfasserin aut Georgi Hudjashov verfasserin aut In EBioMedicine Elsevier, 2015 90(2023), Seite 104536- (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:90 year:2023 pages:104536- https://doi.org/10.1016/j.ebiom.2023.104536 kostenfrei https://doaj.org/article/c68f8d375fea4798817834dfee36df35 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396423001019 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2001 GBV_ILN_2003 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_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 90 2023 104536-
spelling	10.1016/j.ebiom.2023.104536 doi (DE-627)DOAJ087475642 (DE-599)DOAJc68f8d375fea4798817834dfee36df35 DE-627 ger DE-627 rakwb eng R5-920 Tamar Sofer verfasserin aut Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Background: Genome-wide association studies (GWAS) for obstructive sleep apnoea (OSA) are limited due to the underdiagnosis of OSA, leading to misclassification of OSA, which consequently reduces statistical power. We performed a GWAS of OSA in the Million Veteran Program (MVP) of the U.S. Department of Veterans Affairs (VA) healthcare system, where OSA prevalence is close to its true population prevalence. Methods: We performed GWAS of 568,576 MVP participants, stratified by biological sex and by harmonized race/ethnicity and genetic ancestry (HARE) groups of White, Black, Hispanic, and Asian individuals. We considered both BMI adjusted (BMI-adj) and unadjusted (BMI-unadj) models. We replicated associations in independent datasets, and analysed the heterogeneity of OSA genetic associations across HARE and sex groups. We finally performed a larger meta-analysis GWAS of MVP, FinnGen, and the MGB Biobank, totalling 916,696 individuals. Findings: MVP participants are 91% male. OSA prevalence is 21%. In MVP there were 18 and 6 genome-wide significant loci in BMI-unadj and BMI-adj analyses, respectively, corresponding to 21 association regions. Of these, 17 were not previously reported in association with OSA, and 13 replicated in FinnGen (False Discovery Rate p-value < 0.05). There were widespread significant differences in genetic effects between men and women, but less so across HARE groups. Meta-analysis of MVP, FinnGen, and MGB biobank revealed 17 additional, previously unreported, genome-wide significant regions. Interpretation: Sex differences in genetic associations with OSA are widespread, likely associated with multiple OSA risk factors. OSA shares genetic underpinnings with several sleep phenotypes, suggesting shared aetiology and causal pathways. Funding: Described in acknowledgements. Obstructive sleep apnoea Electronic health records Genome-wide association study Sex differences Medicine R Medicine (General) Nuzulul Kurniansyah verfasserin aut Michael Murray verfasserin aut Yuk-Lam Ho verfasserin aut Erik Abner verfasserin aut Tõnu Esko verfasserin aut Jennifer E. Huffman verfasserin aut Kelly Cho verfasserin aut Peter W.F. Wilson verfasserin aut Daniel J. Gottlieb verfasserin aut Andres Metspalu verfasserin aut Lili Milani verfasserin aut Tõnu Esko verfasserin aut Reedik Mägi verfasserin aut Mari Nelis verfasserin aut Georgi Hudjashov verfasserin aut In EBioMedicine Elsevier, 2015 90(2023), Seite 104536- (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:90 year:2023 pages:104536- https://doi.org/10.1016/j.ebiom.2023.104536 kostenfrei https://doaj.org/article/c68f8d375fea4798817834dfee36df35 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396423001019 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2001 GBV_ILN_2003 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_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 90 2023 104536-
allfields_unstemmed	10.1016/j.ebiom.2023.104536 doi (DE-627)DOAJ087475642 (DE-599)DOAJc68f8d375fea4798817834dfee36df35 DE-627 ger DE-627 rakwb eng R5-920 Tamar Sofer verfasserin aut Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Background: Genome-wide association studies (GWAS) for obstructive sleep apnoea (OSA) are limited due to the underdiagnosis of OSA, leading to misclassification of OSA, which consequently reduces statistical power. We performed a GWAS of OSA in the Million Veteran Program (MVP) of the U.S. Department of Veterans Affairs (VA) healthcare system, where OSA prevalence is close to its true population prevalence. Methods: We performed GWAS of 568,576 MVP participants, stratified by biological sex and by harmonized race/ethnicity and genetic ancestry (HARE) groups of White, Black, Hispanic, and Asian individuals. We considered both BMI adjusted (BMI-adj) and unadjusted (BMI-unadj) models. We replicated associations in independent datasets, and analysed the heterogeneity of OSA genetic associations across HARE and sex groups. We finally performed a larger meta-analysis GWAS of MVP, FinnGen, and the MGB Biobank, totalling 916,696 individuals. Findings: MVP participants are 91% male. OSA prevalence is 21%. In MVP there were 18 and 6 genome-wide significant loci in BMI-unadj and BMI-adj analyses, respectively, corresponding to 21 association regions. Of these, 17 were not previously reported in association with OSA, and 13 replicated in FinnGen (False Discovery Rate p-value < 0.05). There were widespread significant differences in genetic effects between men and women, but less so across HARE groups. Meta-analysis of MVP, FinnGen, and MGB biobank revealed 17 additional, previously unreported, genome-wide significant regions. Interpretation: Sex differences in genetic associations with OSA are widespread, likely associated with multiple OSA risk factors. OSA shares genetic underpinnings with several sleep phenotypes, suggesting shared aetiology and causal pathways. Funding: Described in acknowledgements. Obstructive sleep apnoea Electronic health records Genome-wide association study Sex differences Medicine R Medicine (General) Nuzulul Kurniansyah verfasserin aut Michael Murray verfasserin aut Yuk-Lam Ho verfasserin aut Erik Abner verfasserin aut Tõnu Esko verfasserin aut Jennifer E. Huffman verfasserin aut Kelly Cho verfasserin aut Peter W.F. Wilson verfasserin aut Daniel J. Gottlieb verfasserin aut Andres Metspalu verfasserin aut Lili Milani verfasserin aut Tõnu Esko verfasserin aut Reedik Mägi verfasserin aut Mari Nelis verfasserin aut Georgi Hudjashov verfasserin aut In EBioMedicine Elsevier, 2015 90(2023), Seite 104536- (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:90 year:2023 pages:104536- https://doi.org/10.1016/j.ebiom.2023.104536 kostenfrei https://doaj.org/article/c68f8d375fea4798817834dfee36df35 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396423001019 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2001 GBV_ILN_2003 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_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 90 2023 104536-
allfieldsGer	10.1016/j.ebiom.2023.104536 doi (DE-627)DOAJ087475642 (DE-599)DOAJc68f8d375fea4798817834dfee36df35 DE-627 ger DE-627 rakwb eng R5-920 Tamar Sofer verfasserin aut Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Background: Genome-wide association studies (GWAS) for obstructive sleep apnoea (OSA) are limited due to the underdiagnosis of OSA, leading to misclassification of OSA, which consequently reduces statistical power. We performed a GWAS of OSA in the Million Veteran Program (MVP) of the U.S. Department of Veterans Affairs (VA) healthcare system, where OSA prevalence is close to its true population prevalence. Methods: We performed GWAS of 568,576 MVP participants, stratified by biological sex and by harmonized race/ethnicity and genetic ancestry (HARE) groups of White, Black, Hispanic, and Asian individuals. We considered both BMI adjusted (BMI-adj) and unadjusted (BMI-unadj) models. We replicated associations in independent datasets, and analysed the heterogeneity of OSA genetic associations across HARE and sex groups. We finally performed a larger meta-analysis GWAS of MVP, FinnGen, and the MGB Biobank, totalling 916,696 individuals. Findings: MVP participants are 91% male. OSA prevalence is 21%. In MVP there were 18 and 6 genome-wide significant loci in BMI-unadj and BMI-adj analyses, respectively, corresponding to 21 association regions. Of these, 17 were not previously reported in association with OSA, and 13 replicated in FinnGen (False Discovery Rate p-value < 0.05). There were widespread significant differences in genetic effects between men and women, but less so across HARE groups. Meta-analysis of MVP, FinnGen, and MGB biobank revealed 17 additional, previously unreported, genome-wide significant regions. Interpretation: Sex differences in genetic associations with OSA are widespread, likely associated with multiple OSA risk factors. OSA shares genetic underpinnings with several sleep phenotypes, suggesting shared aetiology and causal pathways. Funding: Described in acknowledgements. Obstructive sleep apnoea Electronic health records Genome-wide association study Sex differences Medicine R Medicine (General) Nuzulul Kurniansyah verfasserin aut Michael Murray verfasserin aut Yuk-Lam Ho verfasserin aut Erik Abner verfasserin aut Tõnu Esko verfasserin aut Jennifer E. Huffman verfasserin aut Kelly Cho verfasserin aut Peter W.F. Wilson verfasserin aut Daniel J. Gottlieb verfasserin aut Andres Metspalu verfasserin aut Lili Milani verfasserin aut Tõnu Esko verfasserin aut Reedik Mägi verfasserin aut Mari Nelis verfasserin aut Georgi Hudjashov verfasserin aut In EBioMedicine Elsevier, 2015 90(2023), Seite 104536- (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:90 year:2023 pages:104536- https://doi.org/10.1016/j.ebiom.2023.104536 kostenfrei https://doaj.org/article/c68f8d375fea4798817834dfee36df35 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396423001019 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2001 GBV_ILN_2003 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_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 90 2023 104536-
allfieldsSound	10.1016/j.ebiom.2023.104536 doi (DE-627)DOAJ087475642 (DE-599)DOAJc68f8d375fea4798817834dfee36df35 DE-627 ger DE-627 rakwb eng R5-920 Tamar Sofer verfasserin aut Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Background: Genome-wide association studies (GWAS) for obstructive sleep apnoea (OSA) are limited due to the underdiagnosis of OSA, leading to misclassification of OSA, which consequently reduces statistical power. We performed a GWAS of OSA in the Million Veteran Program (MVP) of the U.S. Department of Veterans Affairs (VA) healthcare system, where OSA prevalence is close to its true population prevalence. Methods: We performed GWAS of 568,576 MVP participants, stratified by biological sex and by harmonized race/ethnicity and genetic ancestry (HARE) groups of White, Black, Hispanic, and Asian individuals. We considered both BMI adjusted (BMI-adj) and unadjusted (BMI-unadj) models. We replicated associations in independent datasets, and analysed the heterogeneity of OSA genetic associations across HARE and sex groups. We finally performed a larger meta-analysis GWAS of MVP, FinnGen, and the MGB Biobank, totalling 916,696 individuals. Findings: MVP participants are 91% male. OSA prevalence is 21%. In MVP there were 18 and 6 genome-wide significant loci in BMI-unadj and BMI-adj analyses, respectively, corresponding to 21 association regions. Of these, 17 were not previously reported in association with OSA, and 13 replicated in FinnGen (False Discovery Rate p-value < 0.05). There were widespread significant differences in genetic effects between men and women, but less so across HARE groups. Meta-analysis of MVP, FinnGen, and MGB biobank revealed 17 additional, previously unreported, genome-wide significant regions. Interpretation: Sex differences in genetic associations with OSA are widespread, likely associated with multiple OSA risk factors. OSA shares genetic underpinnings with several sleep phenotypes, suggesting shared aetiology and causal pathways. Funding: Described in acknowledgements. Obstructive sleep apnoea Electronic health records Genome-wide association study Sex differences Medicine R Medicine (General) Nuzulul Kurniansyah verfasserin aut Michael Murray verfasserin aut Yuk-Lam Ho verfasserin aut Erik Abner verfasserin aut Tõnu Esko verfasserin aut Jennifer E. Huffman verfasserin aut Kelly Cho verfasserin aut Peter W.F. Wilson verfasserin aut Daniel J. Gottlieb verfasserin aut Andres Metspalu verfasserin aut Lili Milani verfasserin aut Tõnu Esko verfasserin aut Reedik Mägi verfasserin aut Mari Nelis verfasserin aut Georgi Hudjashov verfasserin aut In EBioMedicine Elsevier, 2015 90(2023), Seite 104536- (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:90 year:2023 pages:104536- https://doi.org/10.1016/j.ebiom.2023.104536 kostenfrei https://doaj.org/article/c68f8d375fea4798817834dfee36df35 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396423001019 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2001 GBV_ILN_2003 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_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 90 2023 104536-
language	English
source	In EBioMedicine 90(2023), Seite 104536- volume:90 year:2023 pages:104536-
sourceStr	In EBioMedicine 90(2023), Seite 104536- volume:90 year:2023 pages:104536-
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topic_facet	Obstructive sleep apnoea Electronic health records Genome-wide association study Sex differences Medicine R Medicine (General)
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container_title	EBioMedicine
authorswithroles_txt_mv	Tamar Sofer @@aut@@ Nuzulul Kurniansyah @@aut@@ Michael Murray @@aut@@ Yuk-Lam Ho @@aut@@ Erik Abner @@aut@@ Tõnu Esko @@aut@@ Jennifer E. Huffman @@aut@@ Kelly Cho @@aut@@ Peter W.F. Wilson @@aut@@ Daniel J. Gottlieb @@aut@@ Andres Metspalu @@aut@@ Lili Milani @@aut@@ Reedik Mägi @@aut@@ Mari Nelis @@aut@@ Georgi Hudjashov @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
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fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ087475642</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230410124724.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230331s2023 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ebiom.2023.104536</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ087475642</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJc68f8d375fea4798817834dfee36df35</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="050" ind1=" " ind2="0"><subfield code="a">R5-920</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Tamar Sofer</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 of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Summary: Background: Genome-wide association studies (GWAS) for obstructive sleep apnoea (OSA) are limited due to the underdiagnosis of OSA, leading to misclassification of OSA, which consequently reduces statistical power. We performed a GWAS of OSA in the Million Veteran Program (MVP) of the U.S. Department of Veterans Affairs (VA) healthcare system, where OSA prevalence is close to its true population prevalence. Methods: We performed GWAS of 568,576 MVP participants, stratified by biological sex and by harmonized race/ethnicity and genetic ancestry (HARE) groups of White, Black, Hispanic, and Asian individuals. We considered both BMI adjusted (BMI-adj) and unadjusted (BMI-unadj) models. We replicated associations in independent datasets, and analysed the heterogeneity of OSA genetic associations across HARE and sex groups. We finally performed a larger meta-analysis GWAS of MVP, FinnGen, and the MGB Biobank, totalling 916,696 individuals. Findings: MVP participants are 91% male. OSA prevalence is 21%. In MVP there were 18 and 6 genome-wide significant loci in BMI-unadj and BMI-adj analyses, respectively, corresponding to 21 association regions. 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callnumber-first	R - Medicine
author	Tamar Sofer
spellingShingle	Tamar Sofer misc R5-920 misc Obstructive sleep apnoea misc Electronic health records misc Genome-wide association study misc Sex differences misc Medicine misc R misc Medicine (General) Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context
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topic_title	R5-920 Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context Obstructive sleep apnoea Electronic health records Genome-wide association study Sex differences
topic	misc R5-920 misc Obstructive sleep apnoea misc Electronic health records misc Genome-wide association study misc Sex differences misc Medicine misc R misc Medicine (General)
topic_unstemmed	misc R5-920 misc Obstructive sleep apnoea misc Electronic health records misc Genome-wide association study misc Sex differences misc Medicine misc R misc Medicine (General)
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title	Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context
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title_full	Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context
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author_browse	Tamar Sofer Nuzulul Kurniansyah Michael Murray Yuk-Lam Ho Erik Abner Tõnu Esko Jennifer E. Huffman Kelly Cho Peter W.F. Wilson Daniel J. Gottlieb Andres Metspalu Lili Milani Reedik Mägi Mari Nelis Georgi Hudjashov
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title_sort	genome-wide association study of obstructive sleep apnoea in the million veteran program uncovers genetic heterogeneity by sexresearch in context
callnumber	R5-920
title_auth	Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context
abstract	Summary: Background: Genome-wide association studies (GWAS) for obstructive sleep apnoea (OSA) are limited due to the underdiagnosis of OSA, leading to misclassification of OSA, which consequently reduces statistical power. We performed a GWAS of OSA in the Million Veteran Program (MVP) of the U.S. Department of Veterans Affairs (VA) healthcare system, where OSA prevalence is close to its true population prevalence. Methods: We performed GWAS of 568,576 MVP participants, stratified by biological sex and by harmonized race/ethnicity and genetic ancestry (HARE) groups of White, Black, Hispanic, and Asian individuals. We considered both BMI adjusted (BMI-adj) and unadjusted (BMI-unadj) models. We replicated associations in independent datasets, and analysed the heterogeneity of OSA genetic associations across HARE and sex groups. We finally performed a larger meta-analysis GWAS of MVP, FinnGen, and the MGB Biobank, totalling 916,696 individuals. Findings: MVP participants are 91% male. OSA prevalence is 21%. In MVP there were 18 and 6 genome-wide significant loci in BMI-unadj and BMI-adj analyses, respectively, corresponding to 21 association regions. Of these, 17 were not previously reported in association with OSA, and 13 replicated in FinnGen (False Discovery Rate p-value < 0.05). There were widespread significant differences in genetic effects between men and women, but less so across HARE groups. Meta-analysis of MVP, FinnGen, and MGB biobank revealed 17 additional, previously unreported, genome-wide significant regions. Interpretation: Sex differences in genetic associations with OSA are widespread, likely associated with multiple OSA risk factors. OSA shares genetic underpinnings with several sleep phenotypes, suggesting shared aetiology and causal pathways. Funding: Described in acknowledgements.
abstractGer	Summary: Background: Genome-wide association studies (GWAS) for obstructive sleep apnoea (OSA) are limited due to the underdiagnosis of OSA, leading to misclassification of OSA, which consequently reduces statistical power. We performed a GWAS of OSA in the Million Veteran Program (MVP) of the U.S. Department of Veterans Affairs (VA) healthcare system, where OSA prevalence is close to its true population prevalence. Methods: We performed GWAS of 568,576 MVP participants, stratified by biological sex and by harmonized race/ethnicity and genetic ancestry (HARE) groups of White, Black, Hispanic, and Asian individuals. We considered both BMI adjusted (BMI-adj) and unadjusted (BMI-unadj) models. We replicated associations in independent datasets, and analysed the heterogeneity of OSA genetic associations across HARE and sex groups. We finally performed a larger meta-analysis GWAS of MVP, FinnGen, and the MGB Biobank, totalling 916,696 individuals. Findings: MVP participants are 91% male. OSA prevalence is 21%. In MVP there were 18 and 6 genome-wide significant loci in BMI-unadj and BMI-adj analyses, respectively, corresponding to 21 association regions. Of these, 17 were not previously reported in association with OSA, and 13 replicated in FinnGen (False Discovery Rate p-value < 0.05). There were widespread significant differences in genetic effects between men and women, but less so across HARE groups. Meta-analysis of MVP, FinnGen, and MGB biobank revealed 17 additional, previously unreported, genome-wide significant regions. Interpretation: Sex differences in genetic associations with OSA are widespread, likely associated with multiple OSA risk factors. OSA shares genetic underpinnings with several sleep phenotypes, suggesting shared aetiology and causal pathways. Funding: Described in acknowledgements.
abstract_unstemmed	Summary: Background: Genome-wide association studies (GWAS) for obstructive sleep apnoea (OSA) are limited due to the underdiagnosis of OSA, leading to misclassification of OSA, which consequently reduces statistical power. We performed a GWAS of OSA in the Million Veteran Program (MVP) of the U.S. Department of Veterans Affairs (VA) healthcare system, where OSA prevalence is close to its true population prevalence. Methods: We performed GWAS of 568,576 MVP participants, stratified by biological sex and by harmonized race/ethnicity and genetic ancestry (HARE) groups of White, Black, Hispanic, and Asian individuals. We considered both BMI adjusted (BMI-adj) and unadjusted (BMI-unadj) models. We replicated associations in independent datasets, and analysed the heterogeneity of OSA genetic associations across HARE and sex groups. We finally performed a larger meta-analysis GWAS of MVP, FinnGen, and the MGB Biobank, totalling 916,696 individuals. Findings: MVP participants are 91% male. OSA prevalence is 21%. In MVP there were 18 and 6 genome-wide significant loci in BMI-unadj and BMI-adj analyses, respectively, corresponding to 21 association regions. Of these, 17 were not previously reported in association with OSA, and 13 replicated in FinnGen (False Discovery Rate p-value < 0.05). There were widespread significant differences in genetic effects between men and women, but less so across HARE groups. Meta-analysis of MVP, FinnGen, and MGB biobank revealed 17 additional, previously unreported, genome-wide significant regions. Interpretation: Sex differences in genetic associations with OSA are widespread, likely associated with multiple OSA risk factors. OSA shares genetic underpinnings with several sleep phenotypes, suggesting shared aetiology and causal pathways. Funding: Described in acknowledgements.
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title_short	Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context
url	https://doi.org/10.1016/j.ebiom.2023.104536 https://doaj.org/article/c68f8d375fea4798817834dfee36df35 http://www.sciencedirect.com/science/article/pii/S2352396423001019 https://doaj.org/toc/2352-3964
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up_date	2024-07-04T01:51:06.191Z
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fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ087475642</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230410124724.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230331s2023 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ebiom.2023.104536</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ087475642</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJc68f8d375fea4798817834dfee36df35</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="050" ind1=" " ind2="0"><subfield code="a">R5-920</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Tamar Sofer</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 of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Summary: Background: Genome-wide association studies (GWAS) for obstructive sleep apnoea (OSA) are limited due to the underdiagnosis of OSA, leading to misclassification of OSA, which consequently reduces statistical power. We performed a GWAS of OSA in the Million Veteran Program (MVP) of the U.S. Department of Veterans Affairs (VA) healthcare system, where OSA prevalence is close to its true population prevalence. Methods: We performed GWAS of 568,576 MVP participants, stratified by biological sex and by harmonized race/ethnicity and genetic ancestry (HARE) groups of White, Black, Hispanic, and Asian individuals. We considered both BMI adjusted (BMI-adj) and unadjusted (BMI-unadj) models. We replicated associations in independent datasets, and analysed the heterogeneity of OSA genetic associations across HARE and sex groups. We finally performed a larger meta-analysis GWAS of MVP, FinnGen, and the MGB Biobank, totalling 916,696 individuals. Findings: MVP participants are 91% male. OSA prevalence is 21%. In MVP there were 18 and 6 genome-wide significant loci in BMI-unadj and BMI-adj analyses, respectively, corresponding to 21 association regions. Of these, 17 were not previously reported in association with OSA, and 13 replicated in FinnGen (False Discovery Rate p-value < 0.05). There were widespread significant differences in genetic effects between men and women, but less so across HARE groups. Meta-analysis of MVP, FinnGen, and MGB biobank revealed 17 additional, previously unreported, genome-wide significant regions. Interpretation: Sex differences in genetic associations with OSA are widespread, likely associated with multiple OSA risk factors. OSA shares genetic underpinnings with several sleep phenotypes, suggesting shared aetiology and causal pathways. 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Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sexResearch in context

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