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双向孟德尔随机化研究表明银屑病与糖尿病之间不存在遗传联系。

Bidirectional Mendelian Randomization Study Identifies No Genetic Link Between Psoriasis and Diabetes.

作者信息

Li Jing, Li Min, Kong Shoufang, Zhong Chunmei, Sun Danting, Zhang Lili

机构信息

Department of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao, China.

Department of Dermatology, Qingdao Municipal Hospital, Qingdao, China.

出版信息

J Diabetes Res. 2025 Mar 10;2025:9917071. doi: 10.1155/jdr/9917071. eCollection 2025.

Abstract

Epidemiological studies proposed a bidirectional link between psoriasis (Ps) and diabetes mellitus (DM); their causal relationship remains inadequately explored. We obtained summary statistics of genome-wide association analyses for Type 1 diabetes mellitus (T1DM), Type 2 diabetes mellitus (T2DM), and Ps from individuals of European ancestry by accessing the UK Biobank and FinnGen datasets. Inverse-variance weighted (IVW) method was utilized as the primary method. Additional analyses included debiased IVW (dIVW), constrained maximum likelihood with model averaging, robust adjusted profile score, Mendelian randomization (MR)-Egger, weighted median, and weighted mode. Moreover, sensitivity tests were conducted, including Cochran's , MR pleiotropy residual sum, and outlier analyses. Eventually, bidirectional MR was conducted to examine the possibility of a causal link between Ps and DM. No significant causal associations were indicated between DM and Ps. Moreover, there was no causal link between Ps and T1DM. Although certain positive correlations were identified between Ps and T2DM, aggregate evidence remains insufficient to establish a causal relationship. The results demonstrated no evidence of horizontal pleiotropy between genetic variants. Furthermore, a leave-one-out test validated the stability and robustness of this correlation. Our study identifies no genetic causal effect of Ps on DM and of DM on Ps in European ancestry. Additional research is warranted to verify the presence of an association between Ps and DM in diverse populations.

摘要

流行病学研究提出了银屑病(Ps)与糖尿病(DM)之间的双向联系;它们之间的因果关系仍未得到充分探索。我们通过访问英国生物银行和芬兰基因数据集,获得了欧洲血统个体的1型糖尿病(T1DM)、2型糖尿病(T2DM)和银屑病全基因组关联分析的汇总统计数据。采用逆方差加权(IVW)方法作为主要方法。其他分析包括去偏IVW(dIVW)、带模型平均的约束最大似然法、稳健调整轮廓得分、孟德尔随机化(MR)-Egger法、加权中位数和加权众数。此外,还进行了敏感性测试,包括 Cochr an检验、MR多效性残差总和检验和异常值分析。最终,进行了双向MR分析,以检验Ps与DM之间因果联系的可能性。未发现DM与Ps之间存在显著的因果关联。此外,Ps与T1DM之间也没有因果联系。虽然在Ps与T2DM之间发现了某些正相关,但总体证据仍不足以确立因果关系。结果表明基因变异之间不存在水平多效性的证据。此外,留一法检验验证了这种相关性的稳定性和稳健性。我们的研究未发现欧洲血统人群中Ps对DM以及DM对Ps存在遗传因果效应。需要进一步的研究来验证不同人群中Ps与DM之间关联的存在情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d581/11986917/2a75e975718e/JDR2025-9917071.001.jpg

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