Genome-wide meta-analysis and following trans-ethnic replication study identified four novel loci susceptible loci for childhood asthma
Genome-wide meta-analysis and following trans-ethnic replication study identified four novel loci susceptible loci for childhood asthma
Abstract
To identify new susceptible loci for childhood asthma, we carried out a genome-wide meta-analysis in 2,733 Asian population and following trans-ethnic replication study using up to 10,899 individuals from EVE consortium. In the discovery stage, genome-wide meta-analysis combined association summary statistics for about 1.27 millions of imputed and genotyped variants from 1,181 cases and 1,552 controls from Korean and Japanese cohorts. We discovered 77 variants within 21 independent loci with P-value ≤ 5x10-5 including the previously reported pediatric asthma associated loci, HLA-DPB1. A total of 77 variants were taken forward to the replication study. Among them, 70 variants were available in the association data of EVE consortium, investigating asthma-susceptibility genes in European American, African American and Latino ancestry including 5,380 cases and 5,519 controls. As a result, four loci near LMO4, FARS2, FAM155A, and AREL1 were replicated in either of African American or Latino ancestry. The variant near AREL1, a possible eQTL marker, was associated with expression of DLST gene in esophagus tissue. Variants near FARS2 and FAM155A were previously associated with obesity related traits. AREL1 loci was previously reported as IgG glycosylation associated loci. Although 17 loci were failed to be replicated, it is noteworthy that majority of loci were previously associated with IgG glycosylation and lung function. Moreover, most of loci showed consistent direction in genetic effects in the replication study. Taken together, we discovered four novel susceptible loci for childhood asthma and these findings provide new insight to understand hidden pathology of childhood asthma. Acknowledgements: This research was supported by a fund (2017-NG67003-00) by Research of Korea Centers for Disease Control and Prevention, by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare (A092076) and by the Korea Research Foundation Grant funded by the Korean Government (NRF-2010-0025171).