Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.

H. Chen; B.E. Cade; K.J. Gleason; A.C. Bjonnes; A.M. Stilp; T. Sofer; M.P. Conomos; S. Ancoli-Israel; R. Arens; A. Azarbarzin; G.I. Bell; J.E. Below; S. Chun; D.S. Evans; R. Ewert; A.C. Frazier-Wood; S.A. Gharib; J. Haba-Rubio; E.W. Hagen; R. Heinzer; D.R. Hillman; W.C. Johnson; Z. Kutalik; J.M. Lane; E.K. Larkin; S.K. Lee; J. Liang; J.S. Loredo; S. Mukherjee; L.J. Palmer; G.J. Papanicolaou; T. Penzel; P.E. Peppard; W.S. Post; A.R. Ramos; K. Rice; J.I. Rotter; S.A. Sands; N.A. Shah; C. Shin; K.L. Stone; B. Stubbe; J.H. Sul; M. Tafti; K.D. Taylor; A. Teumer; T.A. Thornton; G.J. Tranah; C. Wang; H. Wang; S.C. Warby; D.A. Wellman; P.C. Zee; C.L. Hanis; C.C. Laurie; D.J. Gottlieb; S.R. Patel; X. Zhu; S.R. Sunyaev; R. Saxena; X. Lin; S. Redline

Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.

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doi: 10.1165/rcmb.2017-0237OC
issn: 1044-1549

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Serveur académique Lausannois

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info:eu-repo/semantics/altIdentifier/doi/10.1165/rcmb.2017-0237OC

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info:eu-repo/semantics/altIdentifier/pmid/29077507

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info:eu-repo/semantics/altIdentifier/eissn/1535-4989

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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_6CDA030C63627

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Serveur Académique Lausannois

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Université de Lausanne et CHUV

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info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer

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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

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H. Chen et al., « Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men. », Serveur académique Lausannois, ID : 10.1165/rcmb.2017-0237OC

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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 -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.

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Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.

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