An Exposure-Wide and Mendelian Randomization Approach to Identifying Modifiable Factors for the Prevention of Depression.
An Exposure-Wide and Mendelian Randomization Approach to Identifying Modifiable Factors for the Prevention of Depression.
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DOI：
10.1176/appi.ajp.2020.19111158
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发表时间：
2020-10-01
影响因子：
17.7
通讯作者：
Smoller, Jordan W.
中科院分区：
文献类型：
--
作者：
Choi, Karmel W.;Stein, Murray B.;Nishimi, Kristen M.;Ge, Tian;Coleman, Jonathan R., I;Chen, Chia-Yen;Ratanatharathorn, Andrew;Zheutlin, Amanda B.;Dunn, Erin C.;Breen, Gerome;Koenen, Karestan C.;Smoller, Jordan W.
抑郁症是世界范围内导致残疾的主要原因，预防抑郁症的努力主要集中在有限的候选因素上。研究人员利用来自超过10万名英国生物银行参与者的表型和基因组数据，旨在系统地筛选和验证抑郁症的各种潜在可改变因素。提取了106个可改变因素的基线数据，包括生活方式（例如，锻炼、睡眠、媒体、饮食），社交（例如，支持、参与）和环境（例如，绿地、污染）变量。事件性抑郁定义为基线时的轻微抑郁症状和随访时的临床显著抑郁。根据（i）多基因风险评分，或（ii）报告的创伤性生活事件，确定事件抑郁症的风险个体。进行了一项全社会范围的关联扫描（ExWAS），以确定与全样本和高危人群中的抑郁事件相关的因素。然后使用双样本孟德尔随机化（MR）来验证确定的因素和抑郁症之间的潜在因果关系。社会、睡眠、媒体、饮食和运动相关领域的许多因素都与抑郁症有前瞻性相关，即使在高危人群中也是如此。然而，只有一部分因素得到了MR的验证，包括信任他人（OR=0.76 [0.67-0.86]，p=2.53E-05）、使用电视（OR=1.09 [1.05-1.13]，p=6.81E-06）和白天小睡（OR=1.34 [1.17-1.53]，p=1.82E-05）。使用两个阶段的方法，这项研究验证了几个可操作的目标，以预防抑郁症。它还表明，在观察性研究中，并非所有与抑郁症相关的因素都可以转化为强大的预防目标。一个大规模的全方位的方法结合遗传信息的方法进行因果推理，可能有助于优先考虑精神病学多模式预防的战略。
Efforts to prevent depression—the leading cause of disability worldwide—have focused on a limited number candidate factors. Using phenotypic and genomic data from over 100,000 UK Biobank participants, the authors aimed to systematically screen and validate a wide range of potential modifiable factors for depression. Baseline data were extracted for 106 modifiable factors, including lifestyle (e.g., exercise, sleep, media, diet), social (e.g., support, engagement), and environmental (e.g., greenspace, pollution) variables. Incident depression was defined as minimal depressive symptoms at baseline and clinically significant depression at follow-up. At-risk individuals for incident depression were identified based on (i) polygenic risk scores, or (ii) reported traumatic life events. An exposure-wide association scan (ExWAS) was conducted to identify factors associated with incident depression in the full sample and among at-risk individuals. Two-sample Mendelian randomization (MR) was then used to validate potentially causal relationships between identified factors and depression. Numerous factors across social, sleep, media, dietary, and exercise-related domains were prospectively associated with depression, even among at-risk individuals. However, only a subset of factors was verified by MR, including confiding in others (OR=0.76 [0.67–0.86], p=2.53E-05), TV use (OR=1.09 [1.05–1.13], p=6.81E-06), and daytime napping (OR=1.34 [1.17–1.53], p=1.82E-05). Using a two-stage approach, this study validates several actionable targets for preventing depression. It also demonstrates that not all factors associated with depression in observational research may translate into robust targets for prevention. A large-scale exposure-wide approach combined with genetically informed methods for causal inference may help prioritize strategies for multi-modal prevention in psychiatry.
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DOI：
10.1038/s41366-018-0120-3
发表时间：
2018-06
期刊：
International journal of obesity (2005)
影响因子：
--
作者：
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影响因子：
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发表时间：
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影响因子：
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影响因子：
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