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Hum Mol Genet. 2014 Oct 1;23(19):5251-9. doi: 10.1093/hmg/ddu222. Epub 2014 May 13.

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

Author information

1
Department of Human Genetics ram330@gmail.com nicolae@galton.uchicago.edu.
2
Department of Human Genetics.
3
Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90032, USA.
4
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
5
Department of Medicine and Epidemiology, Johns Hopkins University, Baltimore, MD 21205, USA.
6
International Agency for Research on Cancer, Lyon, France.
7
Department of Public Health Sciences.
8
Department of Medicine and Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143, USA CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
9
BIO5 Institute, Arizona Respiratory Care Center, University of Arizona, Tucson, AZ 85721, USA.
10
National Institute of Public Health of Mexico, Cuernavaca, Morelos, Mexico.
11
Hospital Infantil de Mexico Federico Gómez, Mexico City, Mexico.
12
Center for Health Policy and Health Services Research.
13
Department of Medicine and Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143, USA.
14
Center for Genomics and Personalized Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
15
Center for Health Policy and Health Services Research Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USA.
16
National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
17
Department of Human Genetics Department of Statistics and Medicine, University of Chicago, Chicago, IL 60637, USA ram330@gmail.com nicolae@galton.uchicago.edu.

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.

PMID:
24824216
PMCID:
PMC4159149
DOI:
10.1093/hmg/ddu222
[Indexed for MEDLINE]
Free PMC Article

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