학술논문
Targeted Genome Sequencing Identifies Multiple Rare Variants in Caveolin-1 Associated with Obstructive Sleep Apnea.
Document Type
article
Author
Liang, Jingjing; Wang, Heming; Cade, Brian E; Kurniansyah, Nuzulul; He, Karen Y; Lee, Jiwon; Sands, Scott A; A Brody, Jennifer; Chen, Han; Gottlieb, Daniel J; Evans, Daniel S; Guo, Xiuqing; Gharib, Sina A; Hale, Lauren; Hillman, David R; Lutsey, Pamela L; Mukherjee, Sutapa; Ochs-Balcom, Heather M; Palmer, Lyle J; Purcell, Shaun; Saxena, Richa; Patel, Sanjay R; Stone, Katie L; Tranah, Gregory J; Boerwinkle, Eric; Lin, Xihong; Liu, Yongmei; Psaty, Bruce M; Vasan, Ramachandran S; Manichaikul, Ani; Rich, Stephen S; Rotter, Jerome I; Sofer, Tamar; Redline, Susan; Zhu, Xiaofeng
Source
American Journal of Respiratory and Critical Care Medicine. 206(10)
Subject
Language
Abstract
Rationale: Obstructive sleep apnea (OSA) is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. There is strong clinical and epidemiologic evidence supporting the importance of genetic factors influencing OSA but limited data implicating specific genes. Objectives: To search for rare variants contributing to OSA severity. Methods: Leveraging high-depth genomic sequencing data from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and imputed genotype data from multiple population-based studies, we performed linkage analysis in the CFS (Cleveland Family Study), followed by multistage gene-based association analyses in independent cohorts for apnea-hypopnea index (AHI) in a total of 7,708 individuals of European ancestry. Measurements and Main Results: Linkage analysis in the CFS identified a suggestive linkage peak on chromosome 7q31 (LOD = 2.31). Gene-based analysis identified 21 noncoding rare variants in CAV1 (Caveolin-1) associated with lower AHI after accounting for multiple comparisons (P = 7.4 × 10-8). These noncoding variants together significantly contributed to the linkage evidence (P