Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing 100191, China; National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China; NHC Key Laboratory of Mental Health (Peking University), Beijing 100191, China.
Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing 100191, China; National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China; NHC Key Laboratory of Mental Health (Peking University), Beijing 100191, China.
J Affect Disord. 2023 Jul 15;333:121-129. doi: 10.1016/j.jad.2023.04.079. Epub 2023 Apr 20.
Early sexual intercourse and a greater number of sexual partners have been proved associated with depression. However, the causality of these associations is not clear.
To unveil the causal associations between sexual factors and major depression disorder (MDD). The bidirectional, two-sample Mendelian randomization (MR) study was conducted, which used genetic variants associated with two sexual factors (age first had sexual intercourse, n = 406,457; lifetime number of sexual partners, n = 378,882) and MDD (n = 500,199) from the largest genome-wide association studies (GWASs) conducted by the UK biobank and the Psychiatric Genomics Consortium. The two-step MR analysis was applied to assess mediation. The Genetic predictors for five risky behaviors were also obtained from the most up-to-date GWAS conducted by the UK Biobank (ever self-harmed: 117,733; ever attempted suicide: 4933; psychoactive substance abuse, alcohol use, and tobacco use: 463,010).
MR analysis indicated a risky causal effect of age first had sexual intercourse (OR = 0.720, 95 % CI: 0.661-0.784, P = 2.45 × 10) and lifetime number of sexual partners (OR = 1.656, 95 % CI: 1.356-2.022, P = 7.46 × 10) on MDD. Mediation analysis showed the effects were mediated by tobacco use, with a proportion of 34.20 % on age first had sexual intercourse and 22.94 % on lifetime number of sexual partners separately.
The overlap of participants in different traits and unclear gender.
Robust genetic evidence indicated that premature sexual intercourse and more sexual partners were risks for MDD. Risky behaviors, especially the tobacco use, mediated this effect.
已证实，早期性行为和性伴侣数量较多与抑郁有关。然而，这些关联的因果关系尚不清楚。
为了揭示性因素与重度抑郁症（MDD）之间的因果关系，我们进行了双向、两样本孟德尔随机化（MR）研究，该研究使用了与两种性因素（首次发生性行为的年龄，n=406457；一生的性伴侣数量，n=378882）和 MDD（n=500199）相关的遗传变异，这些数据均来自英国生物库和精神疾病基因组学联合会进行的最大规模全基因组关联研究（GWAS）。采用两步 MR 分析来评估中介作用。还从英国生物库进行的最新 GWAS 中获得了五种危险行为的遗传预测因子（曾自残：117733；曾自杀未遂：4933；精神活性物质滥用、酒精使用和烟草使用：463010）。
MR 分析表明，首次发生性行为的年龄（OR=0.720，95%CI：0.661-0.784，P=2.45×10）和一生的性伴侣数量（OR=1.656，95%CI：1.356-2.022，P=7.46×10）与 MDD 存在风险因果关系。中介分析表明，这些影响可通过吸烟行为来解释，首次发生性行为的年龄和一生的性伴侣数量分别占 34.20%和 22.94%。
不同特征的参与者存在重叠，且性别不明确。
强有力的遗传证据表明，过早的性行为和更多的性伴侣是 MDD 的危险因素。危险行为，特别是吸烟行为，介导了这种影响。
