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

Genome-wide meta-analysis and following trans-ethnic replication study identified four novel loci susceptible loci for childhood asthma

(구연):
Release Date : 2017. 10. 27(금)
Dankyu Yoon1, Kyung Won Kim2, Eun-Jin Kim1, Joo-shil Lee1, Emiko Noguchi3, Carole Ober4, Jeom Kyu Lee1 , Myung Hyun Sohn2
Center for Biomedical Sciences, National Institute of Health, Korea Center for Diseases Control and Prevention, Osong, Korea Division of Allergy and Chronic Respiratory Diseases1
Yonsei Univeresity College of Medicine Department of Pediatrics2
University of Tsukuba, Tsukuba, Japan Department of Medical Genetics3
University of Chicago, Chicago, IL, USA Department of Human Genetics4
윤단규1, 김경원2, 김은진1, 이주실1, Emiko Noguchi3, Carole Ober4, 이점규1 , 손명현2
질병관리본부 국립보건연구원 생명의과학센터 호흡기알레르기질환과 1
연세대학교 의과대학 소아과학교실2
University of Tsukuba Department of Medical Genetics3
Tsukuba Department of Human Genetics4

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).

Keywords: Genome-wide association study, Asthma,