精神障碍与癌症之间的因果关系:孟德尔随机研究

Bowen Du, Han Hong, Chaopeng Tang, Li Fan, Jie Dong, JIngping Ge, Xuejun Shang
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摘要

背景:观察性研究的证据表明,精神障碍与癌症之间存在关联。然而,这种关联的因果关系仍不清楚。研究方法我们从精神病基因组学联合会(PGC,72,517 至 500,199 名参与者)收集了五种精神障碍的全基因组关联研究(GWAS)汇总统计数据,并从英国生物库(167,020 至 361,194 名参与者)和芬兰基因数据库(110,521 至 264,701 名参与者)收集了 18 种癌症风险的 GWAS 汇总统计数据。我们进行了单变量和多变量孟德尔随机化(MR)分析,以探讨其中的因果关系。结果我们发现精神障碍与癌症风险之间存在十种因果关系。值得注意的是,神经性厌食症(AN)与前列腺癌风险降低(β = -0.30,p = 1.61 × 10-6)和胃癌风险升高(β = 0.47,p = 5.3 × 10-3)存在因果关系。双相情感障碍(BD)与胰腺癌风险降低有因果关系(β = -5.13 × 10-4,p = 3.2 × 10-3)。重度抑郁障碍(MDD)与膀胱癌(β = 1.84 × 10-3,p = 5.0 × 10-4)和肾癌(β = 1.40 × 10-3,p = 4.9 × 10-3)风险升高存在因果关系。此外,我们还通过双向磁共振分析发现了皮肤黑色素瘤对 BD(β = -10.39,p = 2.1 × 10-4)和精神分裂症(SCZ,β = -7.42,p = 3.3 × 10-4)的因果效应。此外,通过两步磁共振分析,我们发现白细胞计数是 AN 与胃癌之间因果关系的因果中介。结论:总之,我们的磁共振分析表明,精神障碍与癌症风险存在因果关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Causal Relationship between Mental Disorders and Cancers: a Mendelian Randomization Study
Background: Evidence from observational studies suggests an association between mental disorders and cancers. However, the causality of this association remains unclear. Methods: We collected genome-wide association study (GWAS) summary statistics of five mental disorders from the Psychiatric Genomics Consortium (PGC, 72,517 to 500,199 participants), paired with GWAS summary statistics of the risks of 18 cancer types from the UK Biobank (167,020 to 361,194 participants) and FinnGen database (110,521 to 264,701 participants). We conducted univariable and multivariable Mendelian randomization (MR) analyses to explore the causal relationships. Results: We identified ten causal associations between mental disorders and cancer risks. Notably, anorexia nervosa (AN) exhibits a causal association with a decreased risk of prostate cancer (β = -0.30, p = 1.61 × 10-6) and an elevated risk for stomach cancer (β = 0.47, p = 5.3 × 10-3). Bipolar disorder (BD) is causally linked to a reduced risk of pancreatic cancer (β = -5.13 × 10-4, p = 3.2 × 10-3). Major depression disorder (MDD) is causally associated with an elevated risk of bladder cancer (β = 1.84 × 10-3, p = 5.0 × 10-4) and kidney cancer (β = 1.40 × 10-3, p = 4.9 × 10-3). Additionally, we found the causal effect of skin melanoma on BD (β = -10.39, p = 2.1 × 10-4) and Schizophrenia (SCZ, β = -7.42, p = 3.3 × 10-4) with a bi-directional MR analysis. Moreover, we identified leukocyte count as a causal mediator of a causal association between AN and stomach cancer with a two-step MR analysis. Conclusions: In summary, our MR analysis reveals that mental disorders were causally associated with cancer risks.
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