Genome-Wide Association Study of Suicide Death and Polygenic Prediction of Clinical Antecedents.
Genome-Wide Association Study of Suicide Death and Polygenic Prediction of Clinical Antecedents.
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DOI：
10.1176/appi.ajp.2020.19101025
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发表时间：
2020-10-01
期刊：
影响因子：
--
通讯作者：
Coon H
中科院分区：
文献类型：
--
作者：
Docherty AR;Shabalin AA;DiBlasi E;Monson E;Mullins N;Adkins DE;Bacanu SA;Bakian AV;Crowell S;Chen D;Darlington TM;Callor WB;Christensen ED;Gray D;Keeshin B;Klein M;Anderson JS;Jerominski L;Hayward C;Porteous DJ;McIntosh A;Li Q;Coon H
自杀死亡是一种高度可预防但日益严重的全球健康危机。迄今为止，缺乏足够有力的自杀基因组研究，也没有大量的自杀死亡队列可供研究。为了解决这一局限性，我们利用先前未发表的来自大型人群确定队列的基因型数据，对自杀死亡进行了首次全面的基因组分析。分析样本包括 3,413 个人口确定的欧洲血统病例和 14,810 个祖先匹配的对照。分析方法包括用于祖先匹配和人口分层调整的主成分分析、线性混合模型全基因组关联测试（以遗传相关性矩阵为条件）、基因和基因集富集测试、多基因评分分析以及使用LD评分回归的SNP遗传力和遗传相关性估计。 GWAS 鉴定了两个全基因组显着位点（6 个 SNP，p<5×10–8，包括 rs34399104、rs35518298、rs34053895、rs66828456、rs35502061 和 rs35256367）。基于基因的分析涉及 13、15、16、17 和 19 号染色体上的 22 个基因 (q<0.05)。自杀死亡遗传力估计为 h2SNP = 0.25 (SE = 0.04)，转换为责任量表后为 0.16 (0.02)。值得注意的是，自杀多基因评分具有显着的预测作用。其他几种精神疾病和心理特征的多基因评分也具有预测性，特别是行为抑制解除和重度抑郁症。在本报告中，我们确定了多个全基因组显着位点/基因，并在独立训练和测试集中展示了自杀死亡病例对照状态的多基因评分预测，调整了血统。此外，我们报告说，与对照组相比，自杀死亡病例增加了行为抑制解除、重性抑郁、抑郁症状、自闭症谱系障碍、精神病和酒精使用障碍的遗传风险。
Suicide death 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 study. To address this limitation, we conducted the first comprehensive genomic analysis of suicide death using previously unpublished genotype data from a large, population-ascertained cohort. The analysis sample consisted of 3,413 population-ascertained cases of European ancestry and 14,810 ancestrally matched controls. Analytical methods included principal components 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, polygenic score analyses, as well as SNP heritability and genetic correlation estimation using LD score regression. GWAS identified two genome-wide significant loci (6 SNPs, p<5×10–8, including 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 h2SNP = .25 (SE = .04), and .16 (.02) when converted to a liability scale. Notably, suicide polygenic scores were significantly predictive. Polygenic scores for several other psychiatric disorders and psychological traits were also predictive, particularly behavioral disinhibition and major depressive disorder. In this report, we identify multiple genome-wide significant loci/genes and demonstrate polygenic score prediction of suicide death case-control status, adjusting for ancestry, in independent training and test sets. Additionally, we report that suicide death cases have increased genetic risk for behavioral disinhibition, major depression, depressive symptoms, autism spectrum disorder, psychosis, and alcohol use disorder relative to controls.
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影响因子：
6.2
作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
通讯作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
DOI：
10.1093/bioinformatics/btu848
发表时间：
2015-05-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Euesden J;Lewis CM;O'Reilly PF
通讯作者：
O'Reilly PF
影响因子：
30.8
作者：
Loh, Po-Ru;Danecek, Petr;Palamara, Pier Francesco;Fuchsberger, Christian;Reshef, Yakir A.;Finucane, Hilary K.;Schoenherr, Sebastian;Forer, Lukas;McCarthy, Shane;Abecasis, Goncalo R.;Durbin, Richard;Price, Alkes L.
通讯作者：
Price, Alkes L.