Department of Gastroenterology, Changhai hospital, Naval Medical University, Shanghai 200433, China; National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai 200433, China.
College of Basic Medicine Sciences, Second Military Medical University/Naval Medical University, Shanghai 200433, China.
J Affect Disord. 2025 Jan 1;368:865-871. doi: 10.1016/j.jad.2024.09.030. Epub 2024 Sep 10.
Previous studies have suggested that irritable bowel syndrome (IBS) is strongly associated with psychiatric disorders. However, it is unclear whether this association is causal, concomitant, or accidental. Thus, we performed Mendelian randomization (MR) analysis to evaluate the causal effects of several psychiatric disorders on IBS.
Summary data of genome-wide association studies (GWASs) were obtained mainly from the Psychiatric Genomics Consortium (PGC) on individuals of European ancestry and from a recent GWAS on IBS. We used three MR methods, the inverse-variance weighting (IVW), weighted median (WM), and MR-Egger regression (MR-Egger). In addition, two other indicators, namely, the MR-IVW Cochran's Q statistic and MR-Egger intercept, were used to assess heterogeneity and detect directional horizontal pleiotropy, respectively.
Heritability was high for bipolar disorder (81.18 %, 95 % CI = 73.18-148.18 %), schizophrenia (33.88 %, 95 % CI = 33.57-38.19 %), and panic disorder (30.66 %, 95 % CI = 20.74-40.58 %). For other disorders, there was a low liability-scale SNP heritability for major depressive disorder (MDD) (0.67 %, 95 % CI = 0.61-0.73 %), anxiety disorder (7.63 %, 95 % CI = 1.67-13.59 %), PTSD (0.96 %, 95 % CI = 0.12-1.8 %), and IBS (2.44 %, 95 % CI = 2.13-2.75 %). We also observed that schizophrenia had a significant causal effect on IBS according to MR-IVW. Notably, the individual causal estimates of genetic instruments for MDD and schizophrenia were heterogeneous, but no pleiotropic effects were observed.
Our analyses revealed the causal effects of MDD and schizophrenia on IBS, a matter that has been subject to debate for decades, and also showed that IBS had causal effects on MDD.
先前的研究表明,肠易激综合征(IBS)与精神障碍密切相关。然而,目前尚不清楚这种关联是因果关系、伴随关系还是偶然关系。因此,我们进行了孟德尔随机化(MR)分析,以评估几种精神障碍对 IBS 的因果影响。
我们主要从欧洲血统个体的精神疾病基因组学联盟(PGC)和最近的一项 IBS 全基因组关联研究(GWAS)中获得了全基因组关联研究(GWAS)的汇总数据。我们使用了三种 MR 方法,即逆方差加权(IVW)、加权中位数(WM)和 MR-Egger 回归(MR-Egger)。此外,我们还使用了另外两个指标,即 MR-IVW Cochran's Q 统计量和 MR-Egger 截距,分别评估异质性和检测定向水平的平行性。
双相情感障碍(81.18%,95%CI=73.18-148.18%)、精神分裂症(33.88%,95%CI=33.57-38.19%)和惊恐障碍(30.66%,95%CI=20.74-40.58%)的遗传度较高。对于其他疾病,重度抑郁症(MDD)(0.67%,95%CI=0.61-0.73%)、焦虑症(7.63%,95%CI=1.67-13.59%)、创伤后应激障碍(0.96%,95%CI=0.12-1.8%)和 IBS(2.44%,95%CI=2.13-2.75%)的遗传易感性较低。我们还发现,根据 MR-IVW,精神分裂症对 IBS 有显著的因果影响。值得注意的是,MDD 和精神分裂症的遗传工具的个体因果估计存在异质性,但没有观察到平行性效应。
我们的分析揭示了 MDD 和精神分裂症对 IBS 的因果影响,这是一个几十年来一直存在争议的问题,同时也表明 IBS 对 MDD 有因果影响。