Year: 2014
Type: article
Study design: Observational Study
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.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddu222
Authors: Rachel A. Myers, Nicole M. Scott, W. James Gauderman, Weiliang Qiu, Rasika A. Mathias, Isabelle Romieu, Albert M. Levin, Maria Pino-Yanes, Penelope E. Graves, Albino Barraza Villarreal, Terri H. Beaty, Vincent J. Carey, Damien C. Croteau-Chonka, Blanca del Rio Navarro, Christopher Edlund, Leticia Hernandez-Cadena, Efrain Navarro-Olivos, Badri Padhukasahasram, Muhammad T. Salam, Dara G. Torgerson, David J. Van den Berg, Hita Vora, Eugene R. Bleecker, Deborah A. Meyers, L. Keoki Williams, Fernando D. Martinez, Esteban G. Burchard, Kathleen C. Barnes, Frank D. Gilliland, Scott T. Weiss, Stephanie J. London, Benjamin A. Raby, Carole Ober, Dan L. Nicolae, Jose Rodriguez Santana, William Rodriguez Cintron, Rocio Chapela, Jean Ford, Shannon Thyne, Pedro C. Avila, Juan Jose Sienra Monge, Meher Boorgula, Chris Cheadle, Celeste S. Eng, J. Kiley, S. Banks-Schlegel, W. Gan, on behalf of GRAAD
Institutions: University of Southern California, Brigham and Women's Hospital, Harvard University, Johns Hopkins University, Centre international de recherche sur le cancer, University of California, San Francisco, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, University of Arizona, BIO5 Institute, Instituto Nacional de Salud Pública, Hospital Infantil de México Federico Gómez, Wake Forest University Health Sciences, Wake Forest University, Henry Ford Health, National Institutes of Health, National Institute of Environmental Health Sciences, University of Chicago
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: World Health Organization, Sandler Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities
Awards: G1047949195, Genetics of Asthma In Latino Americans, G1171295685, G1218429807, G1268573537, G1278681517, G1314613728, G1321896751, G1448761013, G1558782472, G1583036818, G1675287001, Pharmacogenetics of Asthma Treatment, G1938493847, G2008013691, The EVE Asthma Genetics Consortium: Building Upon GWAS, Addressing disparities in chronic disease with a teen and young adult focus, G2263518244, A Genome-wide Association Study of Childhood Respiratory Outcomes, G2772107177, G291751459, G3017041733, G3189368323, G3211455882, G3226024509, G3355050153, G3429567754, G3502822211, THE GENETIC EPIDEMIOLOGY OF ASTHMA IN COSTA RICA, G3792659606, G3858807296, G3950177779, G4015031248, G4091359601, G4177996928, G4317585215, G454726209, G457392980, G4672532139, G4799900306, Mechanism of Endotoxin's Effect On Allergy Risk, Air Pollution, Inflammation and New Onset Asthma, G5050719901, PHARMACOGENOMICS OF INHALED CORTICOSTEROID RESPONSIVENESS IN PATIENTS WITH ASTHMA, G5646844712, G6280386340, The Asthma BioRepository for Integrative Genomics Research, G6512022131, Combined Transcriptomics and Genomics to Find Asthma Genes in Admixed Populations, G6582970807, G670838961, G7184647664, G7256948324, G7495004546, G7712917536, G7717732157, Common Genetic Determinants of Asthma and COPD-PROGRAM PROJECT, Genomic Studies of Sex-Specific Architecture of Asthma-Associated Traits, G794209665, G8239800216, G8734275420, G898378059, G9000285380, Environmental Exposures, Host Factors and Human Disease, Immune-driven Airway Epithelial Dysfunction in Muco-obstructive Asthma
OpenAlex ID: W2115904668