Genomics

Dataset Information

32

Meta-analysis Identifies MHC Loci in or near HLA-DRB1, HLA-DQA1, HLA-C as Associated with Leprosy in Chinese Han Population


ABSTRACT: Leprosy is a chronic granulomatous disease caused by infection with Mycobacterium leprae. Genetic association studies indicated that leprosy risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but the full number of variants in this region has yet to be elucidated. To identify further susceptibility loci or loss of function variants for this disease, we performed fine-mapping analysis of the MHC region using a Han Chinese reference panel (n= 10,689 patients, 29,948 genetic markers) in the data sets from our previous leprosy studies. Then, a fixed-effect meta-analysis was carried out separately for Chinese (case=2,901, control=3,801) and North Chinese (case=1,983, control=2,635) participants. The meta-analysis of Chinese participants identified 10 HLA-type or amino acid variants with lower than the genome-wide significant susceptibility signal. Next, gene-by-gene step-wise conditional analysis was performed in the combined dataset of these cohorts. Finally, we identified four new independent susceptibility loci (HLA-DQA1, HLA-C, rs3129063, and rs58327373) and confirmed one previously reported locus (HLA-DRB1) that significantly associated with leprosy in the Chinese Han population. Thus the results of this study increase knowledge about leprosy risk variants and illustrate the value of HLA imputation for fine mapping of causal variants in the MHC. Overall design: To identify further susceptibility loci or loss of function variants for this disease, we performed fine-mapping analysis of the MHC region (29–34 Mb at chromosome 6) using a Han Chinese reference panel (n= 10,689 patients, 29,948 genetic markers) in the data sets from our previous leprosy studies. Then, a fixed-effect meta-analysis was carried out separately for Chinese (case=2,901, control=3,801) and North Chinese (case=1,983, control=2,635) participants. This series includes the 728 cases and 1276 controls hybridized on Illumina Human610-Quad BeadChip in GWAS 1.

INSTRUMENT(S): Illumina Human610-Quad v1.0 BeadChip

SUBMITTER: Xuelei Zhang  

PROVIDER: GSE119367 | GEO | 2018-09-30

REPOSITORIES: GEO

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