Genome-wide association study of suicide attempts in mood disorder patients.
Genome-wide association study of suicide attempts in mood disorder patients.
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DOI：
10.1176/appi.ajp.2010.10040541
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发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
Smoller JW
中科院分区：
文献类型：
--
作者：
Perlis RH;Huang J;Purcell S;Fava M;Rush AJ;Sullivan PF;Hamilton SP;McMahon FJ;Schulze TG;Potash JB;Zandi PP;Willour VL;Penninx BW;Boomsma DI;Vogelzangs N;Middeldorp CM;Rietschel M;Nöthen M;Cichon S;Gurling H;Bass N;McQuillin A;Hamshere M;Wellcome Trust Case Control Consortium Bipolar Disorder Group;Craddock N;Sklar P;Smoller JW
家庭和双胞胎研究表明，自杀企图的倾向是遗传的，与情绪障碍的易感性不同。因此，作者研究了常见的全基因组变异与终生自杀企图之间的关联。作者分析了来自双相I型和II型障碍以及重度抑郁症的全基因组关联研究的终生自杀企图数据。双相情感障碍受试者来自双相情感障碍系统治疗增强项目队列、Wellcome Trust病例对照联盟双相情感障碍队列和伦敦大学学院队列。在NIMH遗传协会信息网络双相情感障碍项目和德国临床队列中进行复制。抑郁症受试者来自缓解抑郁症的序贯治疗替代方案队列，并在荷兰抑郁症和焦虑症研究/荷兰双生子登记抑郁症队列中进行复制。在一个没有确定基因的区域（rs 1466846）观察到双相情感障碍中自杀企图相关性的最强证据; 5个位点也显示出相关性的暗示性证据。在重性抑郁症中，ABI 3BP的单核苷酸多态性观察到最强的关联证据，其中6个位点也显示出暗示性关联。复制队列没有为这些位点提供进一步的支持。然而，纳入约8，700名情绪障碍受试者的荟萃分析确定了另外四个符合暗示性关联阈值的区域，包括含有蛋白激酶C-kD编码基因的基因座，该基因座先前与情绪和焦虑模型有关。结果表明，情绪障碍患者的自杀遗传风险不太可能是个体共同变异的结果。尽管如此，他们提供了多个位点的提示性证据，值得进一步研究。
Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort. Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.
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