Genome-wide association study of asthma in individuals of mixed african ancestry reveals a novel association on chromosome 2q14.
Daya M, Rafaels NM, Chavan S, Boorgula M, Johnston HR, Wilson J, Williams LL, Rotimi C, Ober C, Meyers D, Bleeker E, Ortega VE, Knight-Madden J, Hansel NN, Watson H, Faruque MU, Dunston GM, Caraballo L, Araujo MI, Burchard EG, Taub M, Ruczinski I, Beaty T, Qin ZS, Mathias R, Barnes KC. Genome-wide association study of asthma in individuals of mixed african ancestry reveals a novel association on chromosome 2q14.. Am J Respir Crit Care Med. 2017; 195:A7615.
Am J Respir Crit Care Med.
RATIONALE: Asthma is a complex disease with striking disparities across racial and ethnic groups, which may be partly attributable to genetic factors. One of the main goals of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to discover genes conferring risk to asthma in populations of African descent. METHODS: We performed a genome-wide meta-analysis of asthma association across CAAPA studies (using a total of 4,827 cases and 5,397 controls), genotyped on the African Diaspora Power Chip (ADPC), and imputed using the whole genome sequence reference panel from CAAPA itself. Statistical models appropriate to each study design were used to perform tests for association, and results were combined using the weighted Z-score method. RESULTS: rs787160 and rs17834780 (chromosome 2 hg19 base pair position 144650140 and 144638809 respectively) was significantly associated with asthma case-control status (p=5.07e-09 and 2.44e-08 respectively). These SNPs lie in the intergenic region between the Rho GTPase Activating Protein 15 (ARHGAP15) and Glycosyltransferase Like Domain Containing 1 (GTDC1) genes. ARHGAP15 is expressed in high levels in lymph node cells, peripheral blood mononuclear cells, CD8 T-cells, and B-lymphocytes, while GTDC1 is expressed in high levels in lung and peripheral blood leukocytes. Glycosyltransferase plays a role in the adhesion of environmental factors to epithelial cells, which could in turn play a role in risk to asthma. CONCLUSIONS: We identified a novel asthma association signal on chromosome 2q14 that warrants further investigation.