Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.
Details
Download: Kutalik Manuscript (post-print)-2018.docx.pdf (1247.37 [Ko])
State: Public
Version: Author's accepted manuscript
State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_6CDA030C6362
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.
Journal
American journal of respiratory cell and molecular biology
ISSN
1535-4989 (Electronic)
ISSN-L
1044-1549
Publication state
Published
Issued date
03/2018
Peer-reviewed
Oui
Volume
58
Number
3
Pages
391-401
Language
english
Notes
Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10 <sup>-8</sup> ) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.
Keywords
Adult, Aged, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Phosphatidylethanolamine N-Methyltransferase/genetics, Quantitative Trait Loci/genetics, Sex Characteristics, Sleep Apnea, Obstructive/genetics, Sleep, REM/physiology, Sterol Regulatory Element Binding Protein 1/genetics, Transcription Factors/genetics, ras Proteins/genetics, genetics, genome-wide association studies, multiethnic, obstructive sleep apnea, sexual dimorphism
Pubmed
Web of science
Open Access
Yes
Create date
03/11/2017 17:21
Last modification date
20/08/2019 15:26