Polygenic interactions with environmental adversity in the aetiology of major depressive disorder.
Polygenic interactions with environmental adversity in the aetiology of major depressive disorder.
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DOI：
10.1017/s0033291715002172
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发表时间：
2016-03
影响因子：
6.9
通讯作者：
Lewis CM
中科院分区：
文献类型：
--
作者：
Mullins N;Power RA;Fisher HL;Hanscombe KB;Euesden J;Iniesta R;Levinson DF;Weissman MM;Potash JB;Shi J;Uher R;Cohen-Woods S;Rivera M;Jones L;Jones I;Craddock N;Owen MJ;Korszun A;Craig IW;Farmer AE;McGuffin P;Breen G;Lewis CM
重度抑郁障碍（MDD）是一种常见的致残疾病，具有明确的遗传和环境风险因素。MDD的基因-环境相互作用研究通常研究候选基因，尽管已知该疾病是高度多基因的。本研究旨在检测多基因风险与应激性生活事件（SLEs）或童年创伤（CT）在重度抑郁症病因学中的相互作用。RADIANT UK样本包括1605例MDD病例和1064例具有SLE数据的对照，以及240例CT数据和272例对照。多基因风险评分（PRS）是根据精神病学基因组学协会对重度抑郁症的大型分析结果构建的。测试了PRS和环境因素与病例/控制状态的关系以及它们之间的相互作用。PRS显著预测抑郁，解释表型变异的1.1% （p = 1.9 × 10−6）。SLEs和CT也与MDD状态相关（p = 2.19 × 10−4和p = 5.12 × 10−20）。PRS和SLEs之间没有相互作用。发现显著的PRSxCT相互作用（p = 0.002），但与MDD状态呈负相关，因为经历更严重CT的病例的PRS往往低于其他病例或对照组。在独立的复制样本中没有观察到PRS和CT之间的这种关系。CT是重度抑郁症的一个很强的危险因素，但可能对遗传易感性较低的个体有更大的影响。将环境风险与遗传学一起纳入MDD的病因学研究是非常重要的，而PRS为研究复杂性状中基因与环境的相互作用提供了一种有用的方法。
Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD. The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them. PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples. CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.