Title: Genome-wide interaction studies reveal sex-specific asthma risk alleles.
Authors: Myers, Rachel A; Scott, Nicole M; Gauderman, W James; Qiu, Weiliang; Mathias, Rasika A; Romieu, Isabelle; Levin, Albert M; Pino-Yanes, Maria; Graves, Penelope E; Villarreal, Albino Barraza; Beaty, Terri H; Carey, Vincent J; Croteau-Chonka, Damien C; del Rio Navarro, Blanca; Edlund, Christopher; Hernandez-Cadena, Leticia; Navarro-Olivos, Efrain; Padhukasahasram, Badri; Salam, Muhammad T; Torgerson, Dara G; Van den Berg, David J; Vora, Hita; Bleecker, Eugene R; Meyers, Deborah A; Williams, L Keoki; Martinez, Fernando D; Burchard, Esteban G; Barnes, Kathleen C; Gilliland, Frank D; Weiss, Scott T; London, Stephanie J; Raby, Benjamin A; Ober, Carole; Nicolae, Dan L; GRAAD
Published In Hum Mol Genet, (2014 Oct 01)
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.
PubMed ID: 24824216
MeSH Terms: Alleles*; Asthma/epidemiology; Asthma/genetics*; Chromosome Mapping; Continental Population Groups/genetics; Female; Gene Expression Regulation; Genetic Loci; Genetic Predisposition to Disease*; Genome-Wide Association Study*; Genotype; Humans; Male; Odds Ratio; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Reproducibility of Results; Sex Factors