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Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population.
- Source :
-
Nature genetics [Nat Genet] 2019 Mar; Vol. 51 (3), pp. 470-480. Date of Electronic Publication: 2019 Jan 28. - Publication Year :
- 2019
-
Abstract
- To perform detailed fine-mapping of the major-histocompatibility-complex region, we conducted next-generation sequencing (NGS)-based typing of the 33 human leukocyte antigen (HLA) genes in 1,120 individuals of Japanese ancestry, providing a high-resolution allele catalog and linkage-disequilibrium structure of both classical and nonclassical HLA genes. Together with population-specific deep-whole-genome-sequencing data (nā=ā1,276), we conducted NGS-based HLA, single-nucleotide-variant and indel imputation of large-scale genome-wide-association-study data from 166,190 Japanese individuals. A phenome-wide association study assessing 106 clinical phenotypes identified abundant, significant genotype-phenotype associations across 52 phenotypes. Fine-mapping highlighted multiple association patterns conferring independent risks from classical HLA genes. Region-wide heritability estimates and genetic-correlation network analysis elucidated the polygenic architecture shared across the phenotypes.
Details
- Language :
- English
- ISSN :
- 1546-1718
- Volume :
- 51
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nature genetics
- Publication Type :
- Academic Journal
- Accession number :
- 30692682
- Full Text :
- https://doi.org/10.1038/s41588-018-0336-0