Chen Jinyun, Xu Ting, Wu Min
Department of Rheumatology and Immunology, Third Affiliated Hospital of Soochow University, Changzhou, China.
Front Genet. 2022 Aug 30;13:988022. doi: 10.3389/fgene.2022.988022. eCollection 2022.
Observational studies have found increased incidence of depression, the leading cause of disability worldwide, in patients with systemic lupus erythematosus (SLE). However, it is not clear whether the association was genetically inheritable or caused by modifiable risk factors, such as socioeconomic factors. We investigated the causal relationship between genetically predicted SLE and depression by two-sample Mendelian randomization analysis. Single nucleotide polymorphisms (SNPs) associated with SLE were selected as instrumental variables (IVs) from a genome-wide association study (GWAS) of 14,267 European-ancestry participants. A large GWAS of depression (180,866 European-ancestry participants) and another GWAS of major depressive disorder (MDD) (173,005 European-ancestry participants) were selected as outcomes. Then we estimated the effects of IVs on the odds of depression or MDD by using the inverse-variance weighted (IVW) meta-analysis method (random-effects), which had a power of 90% to detect 4% increase of depression in SLE. Interestingly, genetically predicted SLE decreased the odds of depression [odds ratio (OR): 0.995; 95% CI: 0.990-0.999; = 0.025] and MDD [odds ratio (OR): 0.985; 95% CI: 0.975-0.996; = 0.009], indicating increased depression in SLE was not due to inheritable risk factors.
观察性研究发现，系统性红斑狼疮（SLE）患者中抑郁症的发病率有所上升，而抑郁症是全球致残的主要原因。然而，尚不清楚这种关联是遗传可继承的，还是由社会经济因素等可改变的风险因素引起的。我们通过两样本孟德尔随机化分析研究了遗传预测的SLE与抑郁症之间的因果关系。与SLE相关的单核苷酸多态性（SNP）被选作工具变量（IV），来自一项对14267名欧洲血统参与者的全基因组关联研究（GWAS）。一项针对抑郁症的大型GWAS（180866名欧洲血统参与者）和另一项针对重度抑郁症（MDD）的GWAS（173005名欧洲血统参与者）被选作结果变量。然后，我们使用逆方差加权（IVW）荟萃分析方法（随机效应）估计IV对抑郁症或MDD患病几率的影响，该方法有90%的检验效能来检测SLE中抑郁症增加4%的情况。有趣的是，遗传预测的SLE降低了患抑郁症的几率[比值比（OR）：0.995；95%置信区间：0.990 - 0.999；P = 0.025]和患MDD的几率[比值比（OR）：0.985；95%置信区间：0.975 - 0.996；P = 0.009]，这表明SLE中抑郁症增加并非由于遗传风险因素。
