An association study of suicide and candidate genes in the serotonergic system
An association study of suicide and candidate genes in the serotonergic system
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DOI：
10.1016/j.jad.2012.12.011
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发表时间：
2013-06-01
影响因子：
6.6
通讯作者：
Mors, Ole
中科院分区：
文献类型：
--
作者：
Buttenschon, Henriette N.;Flint, Tracey J.;Mors, Ole
简介：强有力的证据表明，自杀行为的遗传易感性和自杀与精神障碍之间的关系。本研究的目的是测试自杀和五个选定的遗传变异之间的关联，这表明与自杀在其他population.Method：我们进行了一项全国性的病例对照研究，所有的自杀案件送往尸检丹麦之间的2000年和2007年。该研究包括572例病例和1049例对照，是迄今为止最大的自杀基因研究之一。结果：SLC 6A 4、MAOA、TPH 1和TPH 2基因内的遗传标记均与自杀行为无显著相关。探索性交互作用检验显示，TPH 1中rs 1800532的次要等位基因对35岁以下男性和50岁以上女性具有保护作用，而对于年龄最大的男性受试者，它往往是一个危险因素。我们还观察到年龄组和SLC 6A 4中5-HTTLPR基因型（有和没有rs 25531）之间的显着相互作用。长等位基因或高表达等位基因在中年组中往往具有保护作用。局限性：我们只分析了有限数量的遗传变异。结论：分析的变异都不是强危险因素。为了更好地了解自杀基因，我们建议未来的研究应该包括遗传和非遗传因素。(c)2012爱思唯尔有限公司版权所有。
Introduction: Strong evidence demonstrates a genetic susceptibility to suicidal behaviour and a relationship between suicide and mental disorders. The aim of this study was to test for association between suicide and five selected genetic variants, which had shown association with suicide in other populations.Method: We performed a nationwide case-control study on all suicide cases sent for autopsy in Denmark between the years 2000 and 2007. The study comprised 572 cases and 1049 controls and is one of the largest genetic studies in completed suicide to date. The analysed markers were located within the Serotonin Transporter (SLC6A4), Monoamine Oxidase-A (MAOA) and the Ttyptophan Hydroxylase I and II (TPH1 and TPH2) genes.Results: None of the genetic markers within SLC6A4, MAOA, TPH1 and TPH2 were significantly associated with completed suicide or suicide method in the basic association tests. Exploratory interaction test showed that the minor allele of rs1800532 in TPH1 has a protective effect for males younger than 35 years and females older than 50 years, whereas for the oldest male subjects, it tended to be a risk factor. We also observed a significant interaction between age-group and the 5-HTTLPR genotype (with and without rs25531) in SLC6A4. The long allele or high expression allele tends to have a protective effect in the middle age-group.Limitation: We only analysed a limited number of genetic variants.Conclusion: None of the analysed variants are strong risk factors. To reveal a better understanding of the genes involved in suicide, we suggest future studies should include both genetic and non-genetic factors. (c) 2012 Elsevier B.V. All rights reserved.