A cross-population atlas of genetic associations for 220 human phenotypes
A cross-population atlas of genetic associations for 220 human phenotypes
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DOI：
10.1038/s41588-021-00931-x
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发表时间：
2021-09-30
期刊：
影响因子：
30.8
通讯作者：
Okada, Yukinori
中科院分区：
文献类型：
--
作者：
Sakaue, Saori;Kanai, Masahiro;Okada, Yukinori
目前的全基因组关联研究还没有捕捉到足够的多样性的人口和范围的表型。为了扩大非欧洲人群的遗传关联图谱，我们在日本生物银行（n = 179，000）进行了220项深度表型全基因组关联研究（疾病，生物标志物和药物使用），通过整合过去的病史和电子病历的文本挖掘。英国生物银行和FinnGen的荟萃分析（n（总数）= 628，000）确定了5，000个新的基因座，这提高了人类性状基因组图谱的分辨率。该图谱阐明了以主要组织相容性复合体位点为代表的多效性景观，我们在该位点进行了HLA精细定位。最后，我们对全表型汇总统计的矩阵进行了统计分解，并确定了潜在的遗传成分，从而确定了当前人群疾病分类的潜在变异和生物学机制。分解的组分使得能够对类似疾病（例如，过敏性疾病）进行遗传信息的亚型分型。我们的研究为通过遗传学对人类疾病进行无假设的重新调查提供了一条潜在的途径。
Current genome-wide association studies do not yet capture sufficient diversity in populations and scope of phenotypes. To expand an atlas of genetic associations in non-European populations, we conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan (n = 179,000), by incorporating past medical history and text-mining of electronic medical records. Meta-analyses with the UK Biobank and FinnGen (n(total) = 628,000) identified similar to 5,000 new loci, which improved the resolution of the genomic map of human traits. This atlas elucidated the landscape of pleiotropy as represented by the major histocompatibility complex locus, where we conducted HLA fine-mapping. Finally, we performed statistical decomposition of matrices of phenome-wide summary statistics, and identified latent genetic components, which pinpointed responsible variants and biological mechanisms underlying current disease classifications across populations. The decomposed components enabled genetically informed subtyping of similar diseases (for example, allergic diseases). Our study suggests a potential avenue for hypothesis-free re-investigation of human diseases through genetics.