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在英国生物库中鉴定自杀行为的全基因组新关联,与精神障碍的遗传相关性以及与完全自杀的多基因关联。

Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide.

机构信息

Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK; Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.

Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.

出版信息

EBioMedicine. 2019 Mar;41:517-525. doi: 10.1016/j.ebiom.2019.02.005. Epub 2019 Feb 8.

Abstract

BACKGROUND

Suicide is a major issue for global public health. Suicidality describes a broad spectrum of thoughts and behaviours, some of which are common in the general population. Although suicide results from a complex interaction of multiple social and psychological factors, predisposition to suicidality is at least partly genetic.

METHODS

Ordinal genome-wide association study of suicidality in the UK Biobank cohort comparing: 'no suicidality' controls (N = 83,557); 'thoughts that life was not worth living' (N = 21,063); 'ever contemplated self-harm' (N = 13,038); 'act of deliberate self-harm in the past' (N = 2498); and 'previous suicide attempt' (N = 2666).

OUTCOMES

We identified three novel genome-wide significant loci for suicidality (on chromosomes nine, 11 and 13) and moderate-to-strong genetic correlations between suicidality and a range of psychiatric disorders, most notably depression (r 0·81).

INTERPRETATION

These findings provide new information about genetic variants relating to increased risk of suicidal thoughts and behaviours. Future work should assess the extent to which polygenic risk scores for suicidality, in combination with non-genetic risk factors, may be useful for stratified approaches to suicide prevention at a population level. FUND: UKRI Innovation-HDR-UK Fellowship (MR/S003061/1). MRC Mental Health Data Pathfinder Award (MC_PC_17217). MRC Doctoral Training Programme Studentship at the University of Glasgow (MR/K501335/1). MRC Doctoral Training Programme Studentship at the Universities of Glasgow and Edinburgh. UKRI Innovation Fellowship (MR/R024774/1).

摘要

背景

自杀是全球公共卫生的一个主要问题。自杀意念描述了一系列广泛的思想和行为,其中一些在普通人群中很常见。尽管自杀是由多种社会和心理因素复杂相互作用导致的,但自杀倾向至少部分是遗传的。

方法

对英国生物库队列中的自杀意念进行了等级全基因组关联研究,比较了:“无自杀意念”对照组(N=83557);“觉得生活不值得”(N=21063);“曾考虑过自残”(N=13038);“过去曾故意自残”(N=2498);以及“自杀未遂”(N=2666)。

结果

我们确定了三个与自杀意念相关的新的全基因组显著位点(位于染色体 9、11 和 13 上),以及自杀意念与一系列精神障碍(尤其是抑郁症)之间存在中度到高度的遗传相关性(r=0.81)。

解释

这些发现为与自杀意念和行为风险增加相关的遗传变异提供了新的信息。未来的工作应该评估自杀意念的多基因风险评分与非遗传风险因素相结合,在人群层面上对自杀预防进行分层方法的有效性。资金来源:英国研究与创新署 HDR-UK 研究员奖学金(MR/S003061/1)。MRC 心理健康数据探索奖(MC_PC_17217)。格拉斯哥大学 MRC 博士培训计划奖学金(MR/K501335/1)。格拉斯哥大学和爱丁堡大学的 MRC 博士培训计划奖学金。英国研究与创新署创新研究员奖学金(MR/R024774/1)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d035/6442001/d050818f8802/gr1.jpg

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