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Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sex by 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; Tõnu Esko; Reedik Mägi; Mari Nelis; Georgi Hudjashov is a Medicine article available to read on EtoBox.
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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
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- Author
- 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; Tõnu Esko; Reedik Mägi; Mari Nelis; Georgi Hudjashov
- Publisher
- Elsevier BV
- Published
- 2023
- Language
- EN
- Field
- Medicine (Life Sciences)