心境障碍患者自杀未遂的全基因组关联研究。
Genome-wide association study of suicide attempts in mood disorder patients.
机构信息
Department of Psychiatry, Massachusetts General Hospital, Boston, 02114, USA.
出版信息
Am J Psychiatry. 2010 Dec;167(12):1499-507. doi: 10.1176/appi.ajp.2010.10040541. Epub 2010 Nov 1.
OBJECTIVE
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.
METHOD
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.
RESULTS
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.
CONCLUSIONS
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.
目的
家庭和双胞胎研究表明，自杀企图的易感性是可遗传的，与情绪障碍易感性不同。因此，作者研究了常见全基因组变异与终生自杀企图之间的关联。
方法
作者分析了来自双相情感障碍 I 型和 II 型以及重度抑郁症的全基因组关联研究中关于终生自杀企图的数据。双相情感障碍患者来自系统治疗增强计划双相情感障碍队列、惠康信托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 遗传关联信息网络双相情感障碍项目和德国临床队列中进行了复制。抑郁患者来自序贯治疗替代缓解抑郁队列，在荷兰抑郁和焦虑研究/荷兰双胞胎登记抑郁队列中进行了复制。
结果
在没有确定基因的区域（rs1466846）观察到与自杀企图最强的关联证据；五个位点也显示出与关联的迹象。在重度抑郁症中，与 ABI3BP 中的单核苷酸多态性观察到最强的关联证据，六个位点也显示出与关联的迹象。复制队列没有提供这些位点的进一步支持。然而，纳入大约 8700 名情绪障碍患者的荟萃分析确定了另外四个符合提示关联阈值的区域，包括编码蛋白激酶 C-epsilon 的基因所在的区域，该基因先前在情绪和焦虑模型中被涉及。
结论
结果表明，情绪障碍患者自杀的遗传风险不太可能是单个大效应常见变异的结果。然而，它们提供了多个位点的提示性证据，值得进一步研究。
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