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 (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.

中文翻译：

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基因组范围内的自然选择签名与日本人口中现代表型的遗传风险相关。

阐明自然选择特征及其与表型谱的关系对于理解现代人类的适应性进化非常重要。在这里，我们通过使用基于生物库的大规模基因组范围关联的确定的顺序马尔科夫聚结（ASMC）来估计到最近的共同祖先的基因座特定时间，从而对日本人群的选择特征进行了基因组范围的扫描。 170,882名受试者的研究数据。我们确定了29个具有选择签名的基因位点，这些签名满足了全基因组范围的重要性。在4q23（PASMC = 2.2×10-36）的酒精脱氢酶（ADH）基因簇基因座处，签名最为明显，其次是在FAM96A（15q22），MYOF（10q23），13q21，GRIA2（4q32）相对较强的选择，以及ASAP2（2p25）位点（PASMC <1.0×10-10）。询问扩展单倍型（综合单倍型评分）的其他分析显示出所检测特征的鲁棒一致性，有助于基因的精细映射，并提供了选择压力的等位基因定向见解（例如，ADH1B-Arg48His和HLA-DPB1的阳性选择*） 04:01）。全基因组选择富集分析与性状相关的变种，确定了各种现代人类表型参与日本人的适应。我们观察到了与酒精相关的表型，人体测量和生化临床测量以及与免疫相关的疾病致富的特定人群证据，这与使用UK Biobank资源的欧洲人的发现有所不同。我们的研究证明了日语中选择签名的特定人群特征，