Cross–trait analysis of Alzheimer’s disease and gastrointestinal tract disorders identifies shared loci highlighting immune-related and statin pathways

التفاصيل البيبلوغرافية
العنوان: Cross–trait analysis of Alzheimer’s disease and gastrointestinal tract disorders identifies shared loci highlighting immune-related and statin pathways
المؤلفون: Dale R. Nyholt, Eleanor K. O’Brien, Tenielle Porter, Simon M. Laws, Emmanuel Olorunleke Adewuyi
بيانات النشر: Research Square Platform LLC, 2021.
سنة النشر: 2021
مصطلحات موضوعية: Immune system, Statin, business.industry, medicine.drug_class, Medicine, Disease, business, Bioinformatics, Trait analysis, Gastrointestinal tract disorders
الوصف: Several observational studies suggest a relationship between Alzheimer’s disease (AD) and gastrointestinal tract (GIT) disorders; however, their underlying mechanisms remain unclear. Here, we analysed several genome-wide association studies (GWAS) summary statistics (N = 34,652 – 456,327) to assess AD and GIT disorders relationships. We found a significant genetic overlap and correlation between AD and each of gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), medications for GERD or PUD (PGM), gastritis-duodenitis, irritable bowel syndrome and diverticulosis, but not inflammatory bowel disease. Our analysis suggests a partial causal association between AD and gastritis-duodenitis, diverticulosis and medication for PUD. GWAS meta-analysis identified seven loci (P < 5 × 10-8, PDE4B, CD46, SEMA3F, HLA-DRA, MTSS2, PHB, and APOE) shared by AD and PGM, six of which are novel. These loci were replicated using GERD and PUD GWAS and reinforced in gene-based analyses. Lipid metabolism, autoimmune system, lipase inhibitors, PD-1 signalling, and statin pathways were significantly enriched for AD and GIT disorders. These findings support shared genetic susceptibility in AD and GIT disorders. Lipase inhibitors and statins may provide novel therapeutic avenues for AD, GIT disorders, or their comorbidity.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::c8a80e5f11f7f9ab02399d9ba2b5f59c
https://doi.org/10.21203/rs.3.rs-757229/v1
حقوق: OPEN
رقم الأكسشن: edsair.doi...........c8a80e5f11f7f9ab02399d9ba2b5f59c
قاعدة البيانات: OpenAIRE