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, JA, 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
Volume206
Issue10
Pagination1271-1280
Date Published2022 Nov 15
ISSN1535-4970
KeywordsCaveolin 1, High-Throughput Nucleotide Sequencing, Humans, Sequence Analysis, DNA, Sleep Apnea, Obstructive
Abstract

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. To search for rare variants contributing to OSA severity. 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. 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 (Caveolin-1) associated with lower AHI after accounting for multiple comparisons ( = 7.4 × 10). These noncoding variants together significantly contributed to the linkage evidence ( 

DOI10.1164/rccm.202203-0618OC
Alternate JournalAm J Respir Crit Care Med
PubMed ID35822943
PubMed Central IDPMC9746833
Grant ListU01 AG042145 / AG / NIA NIH HHS / United States
U01 AG042124 / AG / NIA NIH HHS / United States
HHSN268201700002C / HL / NHLBI NIH HHS / United States
R35 HL135818 / HL / NHLBI NIH HHS / United States
R01 HL153805 / HL / NHLBI NIH HHS / United States
R01 HL113338 / HL / NHLBI NIH HHS / United States
KL2 RR024990 / RR / NCRR NIH HHS / United States
U01 AG042143 / AG / NIA NIH HHS / United States
HHSN268201700004C / HL / NHLBI NIH HHS / United States
U01 AG027810 / AG / NIA NIH HHS / United States
R01 HL070837 / HL / NHLBI NIH HHS / United States
HHSN268201500015C / HL / NHLBI NIH HHS / United States
R01HG011052 / HG / NHGRI NIH HHS / United States
HHSN268201700005C / HL / NHLBI NIH HHS / United States
U01 AG042140 / AG / NIA NIH HHS / United States
HHSN268201700001C / HL / NHLBI NIH HHS / United States
U01 AG042139 / AG / NIA NIH HHS / United States
R01 HL070841 / HL / NHLBI NIH HHS / United States
K24 HL159246 / HL / NHLBI NIH HHS / United States
R01 HL046380 / HL / NHLBI NIH HHS / United States
R01 HL070838 / HL / NHLBI NIH HHS / United States
R03 HL154284 / HL / NHLBI NIH HHS / United States
R01 HL146697 / HL / NHLBI NIH HHS / United States
R01 HL153814 / HL / NHLBI NIH HHS / United States
HHSN268201700003C / HL / NHLBI NIH HHS / United States

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