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Genome-wide association studies identify polygenic effects for completed suicide in the Japanese population.

ABSTRACT: 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?

SUBMITTER: Otsuka I

PROVIDER: S-EPMC6887868 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Genome-wide association studies identify polygenic effects for completed suicide in the Japanese population.

Otsuka Ikuo I Akiyama Masato M Shirakawa Osamu O Okazaki Satoshi S Momozawa Yukihide Y Kamatani Yoichiro Y Izumi Takeshi T Numata Shusuke S Takahashi Motonori M Boku Shuken S Sora Ichiro I Yamamoto Ken K Ueno Yasuhiro Y Toda Tatsushi T Kubo Michiaki M Hishimoto Akitoyo A

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20190902 12

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 ...[more]

PMID: 31476763

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Project description:ObjectiveDeath by suicide is a highly preventable yet growing worldwide health crisis. To date, there has been a lack of adequately powered genomic studies of suicide, with no sizable suicide death cohorts available for analysis. To address this limitation, the authors conducted the first comprehensive genomic analysis of suicide death using previously unpublished genotype data from a large population-ascertained cohort.MethodsThe analysis sample comprised 3,413 population-ascertained case subjects of European ancestry and 14,810 ancestrally matched control subjects. Analytical methods included principal component analysis for ancestral matching and adjusting for population stratification, linear mixed model genome-wide association testing (conditional on genetic-relatedness matrix), gene and gene set-enrichment testing, and polygenic score analyses, as well as single-nucleotide polymorphism (SNP) heritability and genetic correlation estimation using linkage disequilibrium score regression.ResultsGenome-wide association analysis identified two genome-wide significant loci (involving six SNPs: rs34399104, rs35518298, rs34053895, rs66828456, rs35502061, and rs35256367). Gene-based analyses implicated 22 genes on chromosomes 13, 15, 16, 17, and 19 (q<0.05). Suicide death heritability was estimated at an h2SNP value of 0.25 (SE=0.04) and a value of 0.16 (SE=0.02) when converted to a liability scale. Notably, suicide polygenic scores were significantly predictive across training and test sets. Polygenic scores for several other psychiatric disorders and psychological traits were also predictive, particularly scores for behavioral disinhibition and major depressive disorder.ConclusionsMultiple genome-wide significant loci and genes were identified and polygenic score prediction of suicide death case-control status was demonstrated, adjusting for ancestry, in independent training and test sets. Additionally, the suicide death sample was found to have increased genetic risk for behavioral disinhibition, major depressive disorder, depressive symptoms, autism spectrum disorder, psychosis, and alcohol use disorder compared with the control sample.

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Genome-wide association studies identify polygenic effects for completed suicide in the Japanese population.

Publications

Genome-wide association studies identify polygenic effects for completed suicide in the Japanese population.

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