Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Neuropsychopharmacology. 2019 Nov;44(12):2119-2124. doi: 10.1038/s41386-019-0506-5. Epub 2019 Sep 2.
Suicide is a significant public health problem worldwide, and several Asian countries including Japan have relatively high suicide rates on a world scale. Twin, family, and adoption studies have suggested high heritability for suicide, but genetics lags behind due to difficulty in obtaining samples from individuals who died by suicide, especially in non-European populations. In this study, we carried out genome-wide association studies combining two independent datasets totaling 746 suicides and 14,049 non-suicide controls in the Japanese population. Although we identified no genome-wide significant single-nucleotide polymorphisms (SNPs), we demonstrated significant SNP-based heritability (35-48%; P < 0.001) for completed suicide by genomic restricted maximum-likelihood analysis and a shared genetic risk between two datasets (P = 2.7 × 10) by polygenic risk score analysis. This study is the first genome-wide association study for suicidal behavior in an East Asian population, and our results provided the evidence of polygenic architecture underlying completed suicide.
自杀是一个全球性的重大公共卫生问题，包括日本在内的几个亚洲国家的自杀率在世界范围内相对较高。双胞胎、家庭和收养研究表明，自杀具有很高的遗传性，但由于难以从自杀者身上获取样本，遗传学研究一直滞后，尤其是在非欧洲人群中。在这项研究中，我们对两个独立的数据集进行了全基因组关联研究，这些数据集共包含了日本人群中的 746 名自杀者和 14049 名非自杀对照者。尽管我们没有发现全基因组范围内有意义的单核苷酸多态性（SNPs），但通过基因组受限最大似然分析，我们证明了完全性自杀的 SNP 为基础的遗传力（35-48%；P < 0.001），并且通过多基因风险评分分析，两个数据集之间存在共享的遗传风险（P = 2.7×10）。本研究是首次在东亚人群中对自杀行为进行全基因组关联研究，我们的研究结果为完全性自杀的多基因结构提供了证据。
