GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores
GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores
复制标题
精神疾病自杀未遂的GWAS及其与抑郁症多基因风险评分的关系
DOI：
10.1176/appi.ajp.2019.18080957
复制
发表时间：
2019-08-01
影响因子：
17.7
通讯作者：
Lewis, Cathryn M.
中科院分区：
文献类型：
--
作者：
Mullins, Niamh;Bigdeli, Tim B.;Lewis, Cathryn M.
目的：超过90%企图自杀的人有精神病诊断;然而，双胞胎和家庭研究表明，自杀企图的遗传病因与精神疾病本身部分不同。作者介绍了最大的自杀企图全基因组关联研究（GWAS），使用了来自精神病学基因组学联盟的抑郁症、双相情感障碍和精神分裂症患者队列。1,683名精神分裂症患者和2,946名非精神分裂症患者。通过比较每种疾病的自杀者和非自杀者，对自杀企图进行了GWAS，然后进行了跨疾病的荟萃分析。结果：共发现3个自杀未遂基因位点，其中1个与抑郁症自杀未遂相关，1个与双相情感障碍自杀未遂相关，1个与心境障碍自杀未遂相关。这些关联在英国生物银行和iPSYCH的独立情绪障碍队列中没有复制。在所有三种疾病的荟萃分析中没有发现显著的相关性。抑郁症的多基因风险评分与抑郁症（R-2=0.25%）、双相情感障碍（R-2=0.24%）和精神分裂症（R-2=0.40%）的自杀企图显著相关。结论：本研究提供了关于遗传相关性的新信息，并表明抑郁症的遗传易感性增加了精神疾病自杀企图的风险。进一步的合作努力，以增加样本量可能有助于强有力地确定遗传关联，并提供生物学的见解自杀企图的病因。
Objective: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R-2=0.25%), bipolar disorder (R-2=0.24%), and schizophrenia (R-2=0.40%).Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.