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利用孟德尔随机化探索白癜风与精神障碍之间的遗传关联。

Exploring genetic associations between vitiligo and mental disorders using Mendelian randomization.

机构信息

Department of Dermatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Exp Dermatol. 2024 Jan;33(1):e14979. doi: 10.1111/exd.14979. Epub 2023 Nov 17.

Abstract

Although a large number of existing studies have confirmed that people with vitiligo are prone to mental disorders, these observational studies may be subject to confounding factors and reverse causality, so the true causal relationship is inconclusive. We conducted a bidirectional Mendelian randomization (MR) analysis to assess the causality between vitiligo and mental disorders, namely depression, anxiety, insomnia, schizophrenia, bipolar disorder, obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD). Summary statistics from large available genome-wide association study (GWAS) datasets for generalized vitiligo (n = 44 266), depression (n = 173 005), anxiety (n = 17 310), insomnia (n = 386 988), schizophrenia (n = 130 644), bipolar disorder (n = 413 466), OCD (n = 9725) and ADHD (n = 225 534) were utilized. Inverse-variance weighted (IVW), MR-Egger and weighted median were employed to estimate causal effects. Sensitivity analysis and MR Pleiotropy Residual Sum and Outliers (MR PRESSO) were conducted to assess heterogeneity and pleiotropy, ensuring the robustness of the results. Additionally, we corrected for estimating bias that might be brought on by sample overlap using MRlap. In our findings, none of the rigorous bidirectional MR analyses uncovered a significant causal association. Even after applying the MRlap correction, the effect sizes remained statistically nonsignificant, thereby reinforcing the conclusions drawn via IVW. In summary, our genetic-level investigation did not reveal a causal link between generalized vitiligo and mental disorders.

摘要

尽管大量现有研究证实白癜风患者易患精神障碍,但这些观察性研究可能受到混杂因素和反向因果关系的影响,因此真实的因果关系尚无定论。我们进行了双向孟德尔随机化(MR)分析,以评估白癜风与精神障碍(即抑郁症、焦虑症、失眠症、精神分裂症、双相情感障碍、强迫症和注意缺陷多动障碍)之间的因果关系。从大型可用全基因组关联研究(GWAS)数据集汇总统计数据中提取了广泛性白癜风(n=44266)、抑郁症(n=173005)、焦虑症(n=17310)、失眠症(n=386988)、精神分裂症(n=130644)、双相情感障碍(n=413466)、强迫症(n=9725)和注意缺陷多动障碍(n=225534)的汇总统计数据。我们采用了逆方差加权(IVW)、MR-Egger 和加权中位数来估计因果效应。进行敏感性分析和 MR 偏倚残差和异常值(MR PRESSO)分析以评估异质性和偏倚,确保结果的稳健性。此外,我们使用 MRlap 校正了可能因样本重叠带来的估计偏差。在我们的研究结果中,严格的双向 MR 分析均未发现白癜风与精神障碍之间存在显著的因果关联。即使应用了 MRlap 校正,效应大小仍具有统计学意义,从而通过 IVW 进一步证实了结论。总的来说,我们的遗传水平研究并未揭示出广泛性白癜风与精神障碍之间存在因果关系。

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