Multi-ethnic Meta-analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea Related Quantitative Trait Locus in Men.

TitreMulti-ethnic Meta-analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea Related Quantitative Trait Locus in Men.
Publication TypeJournal Article
Year of Publication2018
AuthorsChen, H, Cade, BE, Gleason, KJ, Bjonnes, AC, Stilp, AM, Sofer, T, Conomos, MP, Ancoli-Israel, S, Arens, R, Azarbarzin, A, Bell, GI, Below, JE, Chun, S, Evans, DS, Ewert, R, Frazier-Wood, AC, Gharib, SA, Haba-Rubio, J, Hagen, EW, Heinzer, R, Hillman, DR, W Johnson, C, Kutalik, Z, Lane, JM, Larkin, EK, Lee, SKu, Liang, J, Loredo, JS, Mukherjee, S, Palmer, LJ, Papanicolaou, GJ, Penzel, T, Peppard, PE, Post, WS, Ramos, AR, Rice, K, Rotter, JI, Sands, SA, Shah, NA, Shin, C, Stone, KL, Stubbe, B, Sul, J-H, Tafti, M, Taylor, KD, Teumer, A, Thornton, TA, Tranah, GJ, Wang, C, Wang, H, Warby, SC, D Wellman, A, Zee, PC, Hanis, CL, Laurie, CC, Gottlieb, DJ, Patel, SR, Zhu, X, Sunyaev, SR, Saxena, R, Lin, X, Redline, S
JournalAmerican journal of respiratory cell and molecular biology
Date Published03/2018
Mots-clésAdult, Aged, Female, genetics, genome-wide association studies, Genome-Wide Association Study, Humans, Male, Middle Aged, multiethnic, obstructive sleep apnea, Obstructive/genetics, Phosphatidylethanolamine N-Methyltransferase/genetics, Quantitative Trait Loci/genetics, ras Proteins/genetics, REM/physiology, Sex Characteristics, sexual dimorphism, Sleep, Sleep Apnea, Sterol Regulatory Element Binding Protein 1/genetics, Transcription Factors/genetics

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. Since 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 multi-ethnic samples. We performed genome-wide association tests for up to 19,733 participants of African-, Asian-, European-, and Hispanic/Latino-American ancestry in seven studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10-8), 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.


Publication Status: aheadofprint

Alternate URL



Alternate JournalAm. J. Respir. Cell Mol. Biol.
Citation Key / SERVAL ID8312
Peer reviewRefereed
PubMed ID29077507


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