Alzheimer's disease as a causal risk factor for diabetic retinopathy: a Mendelian randomization study

作者全名：Ouyang, Fu; Yuan, Ping; Ju, Yaxin; Chen, Wei; Peng, Zijun; Xu, Hongbei

作者地址：[Ouyang, Fu; Yuan, Ping; Chen, Wei; Peng, Zijun; Xu, Hongbei] Guizhou Med Univ, Affiliated Hosp, Guiyang, Guizhou, Peoples R China; [Ju, Yaxin] Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China

通信作者：Xu, HB (通讯作者)，Guizhou Med Univ, Affiliated Hosp, Guiyang, Guizhou, Peoples R China.

来源：FRONTIERS IN ENDOCRINOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001220724500001

JCR分区：Q2

影响因子：3.9

年份：2024

卷号：15

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Alzheimer's disease; diabetic retinopathy; Mendelian randomization; FUMA; causal association

摘要：Objectives This study aims to investigate the causal relationship between Alzheimer's Disease (AD) and Diabetic Retinopathy (DR).Methods Employing Mendelian Randomization (MR), Generalized Summary-data-based Mendelian Randomization (GSMR), and the MR-Steiger test, this study scrutinizes the genetic underpinnings of the hypothesized causal association between AD and DR, as well as its Proliferative DR (PDR) and Non-Proliferative DR (NPDR) subtypes. Comprehensive data from Genome-Wide Association Studies (GWAS) were analyzed, specifically AD data from the Psychiatric Genomics Consortium (71,880 cases/383,378 controls), and DR, PDR, and NPDR data from both the FinnGen consortium (FinnGen release R8, DR: 5,988 cases/314,042 controls; PDR: 8,383 cases/329,756 controls; NPDR: 3,446 cases/314,042 controls) and the IEU OpenGWAS (DR: 14,584 cases/176,010 controls; PDR: 8,681 cases/204,208 controls; NPDR: 2,026 cases/204,208 controls). The study also incorporated Functional Mapping and Annotation (FUMA) for an in-depth analysis of the GWAS results.Results The MR analyses revealed that genetic susceptibility to AD significantly increases the risk of DR, as evidenced by GWAS data from the FinnGen consortium (OR: 2.5090; 95% confidence interval (CI):1.2102-5.2018, false discovery rate P-value (PFDR )=0.0201; GSMR: bxy=0.8936, bxy_se=0.3759, P=0.0174), NPDR (OR: 2.7455; 95% CI: 1.3178-5.7197, PFDR =0.0166; GSMR: bxy=0.9682, bxy_se=0.3802, P=0.0126), and PDR (OR: 2.3098; 95% CI: 1.2411-4.2986, PFDR =0.0164; GSMR: bxy=0.7962, bxy_se=0.3205, P=0.0129) using DR GWAS from FinnGen consortium. These results were corroborated by DR GWAS datasets from IEU OpenGWAS. The MR-Steiger test confirmed a significant association of all identified instrumental variables (IVs) with AD. While a potential causal effect of DR and its subtypes on AD was identified, the robustness of these results was constrained by a low power value. FUMA analysis identified OARD1, NFYA, TREM1 as shared risk genes between DR and AD, suggesting a potential genetic overlap between these complex diseases.Discussion This study underscores the contribution of AD to an increased risk of DR, as well as NPDR and PDR subtypes, underscoring the necessity of a holistic approach in the management of patients affected by these conditions.

基金机构：National Outstanding Youth Science Fund Project of National Natural Science Foundation of China10.13039/100014717

基金资助正文：No Statement Available