期刊
HUMAN MOLECULAR GENETICS
卷 23, 期 19, 页码 5251-5259出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddu222
关键词
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资金
- Office of the Director, National Institutes of Health
- National Heart, Lung and Blood Institute [HL101651, HL085197, HL087699, HL075419, HL65899, HL083069, HL066289, HL101543, HL115606, HL087680, HL61768, HL76647, HL079055, HL118267, HL088133, HL078885, HL004464, HL104608]
- National Institute of Allergy and Infection Diseases [AI079139, AI061774, AI095230, AI077439]
- National Institute of Environmental Health Sciences [ES022719, ES011627, ES007048, ES009581, ES015794]
- National Institute on Minority Health and Health Disparities [MD006902]
- National Institute of General Medical Sciences [GM007546]
- Fundacion Ramon Areces
- American Asthma Foundation
- Fund for Henry Ford Hospital
- Hastings Foundation
- RWJF Amos Medical Faculty Development Award
- Sandler Foundation
- Mary Beryl Patch Turnbull Scholar Program
- National Institutes of Health, National Institute of Environmental Health Sciences
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 x 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.
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