Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Human molecular genetics, 2014-10, Vol.23 (19), p.5251-5259

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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.