Giulio Maria Pasinetti
Icahn School of Medicine at Mount Sinai, USA
Posters & Accepted Abstracts: J Diabetes Metab
Epidemiological evidence supports the observation that subjects with type-2 diabetes (T2D) is at higher risk to develop Alzheimer�??s disease (AD). However, how these two conditions are causally linked is unknown. Possible mechanisms include shared genetic risk factors, which we investigated in a recent study based on recent genome wide association study (GWAS) findings. We retrieved single nucleotide polymorphisms (SNPs) associated with T2D and AD from large-scale GWAS meta-analysis consortia and tested for overlap among the T2D and AD associated SNPs. We found 927 SNPs associated with both AD and T2D with p-value�?�0.01, an overlap significantly larger than random chance (overlapping p-value of 6.93E-28). Among these, 395 of the shared GWAS SNPs have the same risk allele for AD and T2D, suggesting common pathogenic mechanisms underlying the development of both AD and T2D. We found that gene annotations from these shared SNPs are significantly enriched for specific KEGG pathways pertaining to immune responses, cell signaling and neuronal plasticity and cellular processes in which abnormalities are known to contribute to both T2D and AD pathogenesis. Our observation suggests that among T2D subjects with common genetic predispositions, dysregulation of these pathogenic pathways could have contributed to the onset of T2D, while simultaneously contributing to the increased risks of these subjects to eventually develop AD. Collectively, our GWAS studies will bring up to date one of the most important issues related to the influences of genetics on why some individuals with T2D are at high risk for developing AD.
Email: giulio.pasinetti@mssm.edu
