Unraveling the Genetic Comorbidity Landscape of Alzheimer’s Disease

Alzheimer’s disease (AD) has emerged as the most prevalent and complex neurodegenerative disorder among the elderly population. However, the genetic comorbidity etiology for AD remains poorly understood. In this study, we conducted pleiotropic analysis for 41 AD phenotypic comorbidities, identifying ten genetic comorbidities with 16 pleiotropy genes associated with AD. Through biological functional and network analysis, we elucidated the molecular and functional landscape of AD genetic comorbidities. Furthermore, leveraging the pleiotropic genes and reported biomarkers for AD genetic comorbidities, we identified 50 potential biomarkers for AD diagnosis. Our findings deepen the understanding of the occurrence of AD genetic comorbidities and provide new insights for the search for AD diagnostic markers. Highlights The present study has focused on the comorbidities associated with Alzheimer’s disease (AD) by constructing a landscape of these comorbidities at various levels, including diseases, genetics, and pathways. The study findings reveal novel and significant pathways that contribute to the etiology of AD and its comorbidities. By exploring pleiotropic genes and reported biomarkers of AD comorbidities, the study has identified several potential diagnostic biomarker candidates for AD. Abstract Figure Graphic abstract. Study pipeline.