Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.
Détails
Télécharger: Kutalik Manuscript (post-print)-2018.docx.pdf (1247.37 [Ko])
Etat: Public
Version: Author's accepted manuscript
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_6CDA030C6362
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.
Périodique
American journal of respiratory cell and molecular biology
ISSN
1535-4989 (Electronic)
ISSN-L
1044-1549
Statut éditorial
Publié
Date de publication
03/2018
Peer-reviewed
Oui
Volume
58
Numéro
3
Pages
391-401
Langue
anglais
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
Résumé
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.
Mots-clé
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
Oui
Création de la notice
03/11/2017 16:21
Dernière modification de la notice
20/08/2019 14:26