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Updated: Jun 7, 2025

Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
Published on: January 9, 2020
Genetic variants for Alzheimer's disease and comorbid conditions
Minmin Pan1, Dongbing Lai2, Frederick Unverzagt3
1Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA.
Background:
Alzheimer's disease and related dementias (ADRD) frequently co-occur with comorbidities such as diabetes and cardiovascular diseases in elderly populations.
Objective:
Utilize a life-course approach to identify genetic variants that are associated with the co-occurrence of ADRD and another comorbid condition.
Methods:
Research data from African American participants of the Indianapolis-Ibadan Dementia Project (IIDP) linked with electronic medical record (EMR) data and genome-wide association study (GWAS) data were utilized. The age of onset for ADRD was obtained from longitudinal follow-up of the IIDP study. Age of onset for comorbid conditions was obtained from EMR. The analysis included 1177 African Americans, among whom 174 were diagnosed with ADRD. A semi-parametric marginal bivariate survival model was used to examine the influence of single nucleotide polymorphisms (SNPs) on dual time-to-event outcomes while adjusting for sex, years of education, and the first principal component of GWAS data.
Results:
Targeted analysis of 20 SNPs that were reported to be associated with ADRD revealed that six were significantly associated with dual-disease outcomes, specifically congestive heart failure and cancer. In addition, eight novel SNPs were identified for associations with both ADRD and a comorbid condition.
Conclusions:
Using a bivariate survival model approach, we identified genetic variants associated not only with ADRD, but also with comorbid conditions. Our utilization of dual-disease models represents a novel analytic strategy for uncovering shared genetic variants for multiple disease phenotypes.
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