Loneliness and depression: bidirectional mendelian randomization analyses using data from three large genome-wide association studies.
Loneliness and depression: bidirectional mendelian randomization analyses using data from three large genome-wide association studies.
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DOI：
10.1038/s41380-023-02259-w
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发表时间：
2023-09
影响因子：
11
通讯作者：
D. Sbarra;Ferris A Ramadan;Karmel W Choi;J. Treur;D. Levey;R. Wootton;M. Stein;J. Gelernter;Yann C Klimentidis
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文献类型：
--
作者：
D. Sbarra;Ferris A Ramadan;Karmel W Choi;J. Treur;D. Levey;R. Wootton;M. Stein;J. Gelernter;Yann C Klimentidis
重度抑郁症（MD）是一种严重的精神疾病，困扰着世界上近5%的人口。大量的相关文献表明，孤独是MD的一个潜在危险因素;这种性质的相关性可能会因各种原因而混淆。本报告使用孟德尔随机化（MR）来研究孤独和MD之间的潜在因果关系。我们报告了三个大型全基因组关联研究（GWAS）的汇总统计分析。使用三个独立来源的GWAS汇总统计量进行MR分析。在第一组分析中，我们使用了现有的孤独感GWAS的汇总统计数据来预测MD风险。我们使用了两个结果数据来源：精神病基因组学联盟（PGC）MD荟萃分析（PGC-MD;N= 142，646）和百万退伍军人计划（MVP-MD;N= 250，215）。最后，我们使用MVP和PGC样本的数据进行反向分析，以确定MD的风险变体，并使用英国生物银行的孤独结果数据。我们发现了强有力的证据表明孤独和MD之间存在双向因果关系，包括孤独，抑郁症病例状态和抑郁症状的连续测量之间的因果关系。在几个敏感性分析中，包括解释水平多效性的模型，估计值仍然显着。这篇论文提供了第一个遗传学证据，证明减少孤独感可能在降低抑郁症风险方面发挥因果作用，这些发现支持减少孤独感以预防或改善MD的努力。讨论的重点是这些发现的公共卫生意义，特别是在SARS-CoV-2大流行的情况下。
Major depression (MD) is a serious psychiatric illness afflicting nearly 5% of the world’s population. A large correlational literature suggests that loneliness is a prospective risk factor for MD; correlational assocations of this nature may be confounded for a variety of reasons. This report uses Mendelian Randomization (MR) to examine potentially causal associations between loneliness and MD. We report on analyses using summary statistics from three large genome wide association studies (GWAS). MR analyses were conducted using three independent sources of GWAS summary statistics. In the first set of analyses, we used available summary statistics from an extant GWAS of loneliness to predict MD risk. We used two sources of outcome data: the Psychiatric Genomics Consortium (PGC) meta-analysis of MD (PGC-MD;N= 142,646) and the Million Veteran Program (MVP-MD;N= 250,215). Finally, we reversed analyses using data from the MVP and PGC samples to identify risk variants for MD and used loneliness outcome data from UK Biobank. We find robust evidence for a bidirectional causal relationship between loneliness and MD, including between loneliness, depression cases status, and a continuous measure of depressive symptoms. The estimates remained significant across several sensitivity analyses, including models that account for horizontal pleiotropy. This paper provides the first genetically-informed evidence that reducing loneliness may play a causal role in decreasing risk for depressive illness, and these findings support efforts to reduce loneliness in order to prevent or ameliorate MD. Discussion focuses on the public health significance of these findings, especially in light of the SARS-CoV-2 pandemic.