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Genome-wide interaction studies reveal sex-specific asthma risk alleles.

ABSTRACT: Asthma is a complex disease with sex-specific differences in prevalence. Candidate gene studies have suggested that genotype-by-sex interaction effects on asthma risk exist, but this has not yet been explored at a genome-wide level. We aimed to identify sex-specific asthma risk alleles by performing a genome-wide scan for genotype-by-sex interactions in the ethnically diverse participants in the EVE Asthma Genetics Consortium. We performed male- and female-specific genome-wide association studies in 2653 male asthma cases, 2566 female asthma cases and 3830 non-asthma controls from European American, African American, African Caribbean and Latino populations. Association tests were conducted in each study sample, and the results were combined in ancestry-specific and cross-ancestry meta-analyses. Six sex-specific asthma risk loci had P-values < 1 × 10(-6), of which two were male specific and four were female specific; all were ancestry specific. The most significant sex-specific association in European Americans was at the interferon regulatory factor 1 (IRF1) locus on 5q31.1. We also identify a Latino female-specific association in RAP1GAP2. Both of these loci included single-nucleotide polymorphisms that are known expression quantitative trait loci and have been associated with asthma in independent studies. The IRF1 locus is a strong candidate region for male-specific asthma susceptibility due to the association and validation we demonstrate here, the known role of IRF1 in asthma-relevant immune pathways and prior reports of sex-specific differences in interferon responses.

SUBMITTER: Myers RA

PROVIDER: S-EPMC4159149 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Genome-wide interaction studies reveal sex-specific asthma risk alleles.

Myers Rachel A RA Scott Nicole M NM Gauderman W James WJ Qiu Weiliang W Mathias Rasika A RA Romieu Isabelle I Levin Albert M AM Pino-Yanes Maria M Graves Penelope E PE Villarreal Albino Barraza AB Beaty Terri H TH Carey Vincent J VJ Croteau-Chonka Damien C DC del Rio Navarro Blanca B Edlund Christopher C Hernandez-Cadena Leticia L Navarro-Olivos Efrain E Padhukasahasram Badri B Salam Muhammad T MT Torgerson Dara G DG Van den Berg David J DJ Vora Hita H Bleecker Eugene R ER Meyers Deborah A DA Williams L Keoki LK Martinez Fernando D FD Burchard Esteban G EG Barnes Kathleen C KC Gilliland Frank D FD Weiss Scott T ST London Stephanie J SJ Raby Benjamin A BA Ober Carole C Nicolae Dan L DL

Human molecular genetics 20140513 19

Asthma is a complex disease with sex-specific differences in prevalence. Candidate gene studies have suggested that genotype-by-sex interaction effects on asthma risk exist, but this has not yet been explored at a genome-wide level. We aimed to identify sex-specific asthma risk alleles by performing a genome-wide scan for genotype-by-sex interactions in the ethnically diverse participants in the EVE Asthma Genetics Consortium. We performed male- and female-specific genome-wide association studie ...[more]

PMID: 24824216

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Genome-wide interaction studies reveal sex-specific asthma risk alleles.

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Genome-wide interaction studies reveal sex-specific asthma risk alleles.

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