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Mol Biol Evol. 2020 Jan 20. pii: msaa005. doi: 10.1093/molbev/msaa005. [Epub ahead of print]

Genome-wide natural selection signatures are linked to genetic risk of modern phenotypes in the Japanese population.

Author information

1
Faculty of Medicine, Osaka University, Suita, Japan.
2
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
3
Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
4
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
5
Department of Computational Biology and Medical Sciences, Graduate school of Frontier Sciences, the University of Tokyo, Tokyo, Japan.
6
Division of Molecular Pathology, the Institute of Medical Sciences, the University of Tokyo, Tokyo, Japan.
7
RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
8
Department of Statistics, University of Oxford, Oxford OX13LB, UK.
9
Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Tokyo, Japan.
10
Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
11
Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University.

Abstract

Elucidation of natural selection signatures and relationships with phenotype spectra is important to understand adaptive evolution of modern humans. Here, we conducted a genome-wide scan of selection signatures of the Japanese population by estimating locus-specific time to the most recent common ancestor using the ascertained sequentially Markovian coalescent (ASMC), from the biobank-based large-scale genome-wide association study data of 170,882 subjects. We identified 29 genetic loci with selection signatures satisfying the genome-wide significance. The signatures were most evident at the alcohol dehydrogenase (ADH) gene cluster locus at 4q23 (PASMC = 2.2 × 10-36), followed by relatively strong selection at the FAM96A (15q22), MYOF (10q23), 13q21, GRIA2 (4q32), and ASAP2 (2p25) loci (PASMC < 1.0 × 10-10). The additional analysis interrogating extended haplotypes (iHS) showed robust concordance of the detected signatures, contributing to fine-mapping of the genes, and provided allelic directional insights into selection pressure (e.g., positive selection for ADH1B-Arg48His and HLA-DPB1*04:01). The phenome-wide selection enrichment analysis with the trait-associated variants identified a variety of the modern human phenotypes involved in the adaptation of Japanese. We observed population-specific evidence of enrichment with the alcohol related phenotypes, anthropometric and biochemical clinical measurements, and immune-related diseases, differently from the findings in Europeans using the UK Biobank resource. Our study demonstrated population-specific features of the selection signatures in Japanese, highlighting a value of the natural selection study using the nation-wide biobank-scale genome and phenotype data.

PMID:
31957793
DOI:
10.1093/molbev/msaa005

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