In:
Molecular Biology and Evolution, Oxford University Press (OUP), Vol. 37, No. 5 ( 2020-05-01), p. 1306-1316
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 & lt; 1.0 × 10−10). The additional analysis interrogating extended haplotypes (integrated haplotype score) 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.
Type of Medium:
Online Resource
ISSN:
0737-4038
,
1537-1719
DOI:
10.1093/molbev/msaa005
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2020
detail.hit.zdb_id:
2024221-9
SSG:
12
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