Polygenic scores for obstructive sleep apnoea reveal pathways contributing to cardiovascular disease

作者：Nuzulul Kurniansyah, Satu J. Strausz, Geetha Chittoor, Shreyash Gupta, Anne E. Justice, Yana Hrytsenko, Brendan T Keenan, Brian E. Cade, Brian Spitzer, Heming Wang, Jennifer E. Huffman, Matthew R. Moll, Bernhard Haring, Su Yon Jung, Laura M. Raffield, Robert C. Kaplan, Jerome I Rotter, Stephen S. Rich, Sina A. Gharib, Traci M. Bartz, Peter Y. Liu, Han Chen, Myriam Fornage, Lifang Hou, Daniel A. Levy, Alanna C. Morrison, Heather M. Ochs‐Balcom, Bruce M. Psaty, Peter W F Wilson, Kelly Cho, Allan I Pack, Hanna Maria Ollila, Susan S Redline, Daniel J. Gottlieb, Tamar Sofer · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2025.105790 · 被引用次数：9 · 研究领域：Obstructive Sleep Apnea Research、Genetic Associations and Epidemiology、Cardiovascular Disease and Adiposity

BACKGROUND: Obstructive sleep apnoea (OSA) is a common chronic condition, with obesity its strongest risk factor. Polygenic scores (PGSs) summarise the genetic liability to phenotype and can provide insights into relationships between phenotypes. Recently, large datasets that include genetic data and OSA status became available, providing an opportunity to utilise PGS approaches to study the genetic relationship between OSA and other phenotypes, while differentiating OSA-specific from obesity-specific genetic factors. METHODS: Using race/ethnic diverse samples from over 1.2 million individuals from the Million Veteran Program, FinnGen, TOPMed, All of Us (AoU), Geisinger's MyCode, MGB Biobank, and the Human Phenotype Project, we developed and assessed PGSs for OSA, both without (BMIunadjOSA-PGS) and with adjustment for the genetic contributions of BMI (BMIadjOSA-PGS). FINDINGS: Adjusted odds ratios (ORs) for OSA per 1 standard deviation of the PGSs ranged from 1.38 to 2.75. The associations of BMIadjOSA- and BMIunadjOSA-PGSs with CVD outcomes in AoU shared both common and distinct patterns. Only BMIunadjOSA-PGS was associated with type 2 diabetes, heart failure, and coronary artery disease, while both BMIadjOSA- and BMIunadjOSA-PGSs were associated with hypertension and stroke. Sex stratified analyses revealed that BMIadjOSA-PGS association with hypertension was driven by females (OR = 1.1, p-value = 0.002, OR = 1.01 p-value = 0.2 in males). OSA PGSs were also associated with ...