Pulse lineResearch With Heart Logo

Targeted Genome Sequencing Identifies Multiple Rare Variants in Caveolin-1 Associated with Obstructive Sleep Apnea.

TitleTargeted Genome Sequencing Identifies Multiple Rare Variants in Caveolin-1 Associated with Obstructive Sleep Apnea.
Publication TypeJournal Article
Year of Publication2022
AuthorsLiang J, Wang H, Cade BE, Kurniansyah N, He KY, Lee J, Sands SA, Brody J, Chen H, Gottlieb DJ, Evans DS, Guo X, Gharib SA, Hale L, Hillman DR, Lutsey PL, Mukherjee S, Ochs-Balcom HM, Palmer LJ, Purcell S, Saxena R, Patel SR, Stone KL, Tranah GJ, Boerwinkle E, Lin X, Liu Y, Psaty BM, Vasan RS, Manichaikul A, Rich SS, Rotter JI, Sofer T, Redline S, Zhu X
Corporate AuthorsTOPMed Sleep Working Group
JournalAm J Respir Crit Care Med
Date Published2022 Jul 13

INTRODUCTION: Obstructive sleep apnea (OSA) is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. There is strong clinical and epi-demiologic evidence supporting the importance of genetic factors influencing OSA, but limited data implicating specific genes.

METHODS: Leveraging high depth genomic sequencing data from the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program and imputed genotype data from multiple population-based studies, we performed linkage analysis in the Cleve-land Family Study (CFS) followed by multi-stage gene-based association analyses in independent cohorts to search for rare variants contributing to OSA severity as assessed by the apnea-hypopnea index (AHI) in a total of 7,708 individuals of European ancestry.

RESULTS: Linkage analysis in CFS identified a suggestive linkage peak on chromosome 7q31 (LOD=2.31). Gene-based analysis identified 21 non-coding rare variants in Caveolin-1 (CAV1) associated with lower AHI after accounting for multiple comparisons (p=7.4×10-8). These non-coding variants together significantly contributed to the linkage evidence (p

CONCLUSION: Rare variants in CAV1, a membrane scaffolding protein essential in multiple cellular and metabolic functions, are associated with higher CAV1 gene expression and lower OSA severity, suggesting a novel target for modulating OSA severity.

Alternate JournalAm J Respir Crit Care Med
PubMed ID35822943
Grant ListR01 HL153814 / HL / NHLBI NIH HHS / United States