Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases
Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases
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DOI：
10.1038/s41588-018-0047-6
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发表时间：
2018-03-01
期刊：
影响因子：
30.8
通讯作者：
Kamatani, Yoichiro
中科院分区：
文献类型：
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作者：
Kanai, Masahiro;Akiyama, Masato;Kamatani, Yoichiro
临床测量可被视为有用的中间表型，以促进对复杂人类疾病的理解。为了全面深入了解潜在的遗传学因素，我们在此对162255名日本个体的58个数量性状进行了全基因组关联研究（GWAS）。总体而言，我们确定了1407个与性状相关的基因座（P < 5.0×10⁻⁸），其中679个是新的。通过纳入日本个体中32项关于复杂疾病和性状的其他GWAS结果，我们进一步强调了数量性状和疾病之间的多效性、遗传相关性以及细胞类型特异性，这极大地拓展了当前对相关遗传学和生物学的理解。这项研究确定了共享的多基因效应和细胞类型特异性，体现在临床测量、复杂疾病和相关细胞类型之间的遗传联系上。我们的研究结果表明，即使没有跨表型关系的先验生物学知识，与临床测量相对应的遗传学也能成功地重现这些测量与疾病的相关性，从而有助于阐明未知的病因和发病机制。
Clinical measurements can be viewed as useful intermediate phenotypes to promote understanding of complex human diseases. To acquire comprehensive insights into the underlying genetics, here we conducted a genome-wide association study (GWAS) of 58 quantitative traits in 162,255 Japanese individuals. Overall, we identified 1,407 trait-associated loci (P < 5.0 x 10(-8)), 679 of which were novel. By incorporating 32 additional GWAS results for complex diseases and traits in Japanese individuals, we further highlighted pleiotropy, genetic correlations, and cell-type specificity across quantitative traits and diseases, which substantially expands the current understanding of the associated genetics and biology. This study identified both shared polygenic effects and cell-type specificity, represented by the genetic links among clinical measurements, complex diseases, and relevant cell types. Our findings demonstrate that even without prior biological knowledge of cross-phenotype relationships, genetics corresponding to clinical measurements successfully recapture those measurements' relevance to diseases, and thus can contribute to the elucidation of unknown etiology and pathogenesis.