Key result
Analysis identified 6 known and 8 novel single nucleotide polymorphisms significantly associated with the co-occurrence of ADRD and comorbid conditions such as congestive heart failure and cancer.
Why the study?
ADRD frequently co-occurs with comorbidities such as diabetes and cardiovascular diseases in elderly populations, prompting the use of a life-course approach to identify associated genetic variants.
Which genetic variants are associated with the co-occurrence of Alzheimer's disease and related dementias (ADRD) and comorbid conditions in African Americans?
Observational (n=1,177)
Yes
Which genetic variants are associated with the co-occurrence of Alzheimer's disease and related dementias (ADRD) and comorbid conditions in African Americans?
A bivariate survival model identified shared genetic variants associated with both Alzheimer's disease and comorbid conditions like congestive heart failure in African Americans.
Answers are grounded in this paper and cite their sources.
May inform genetic risk assessment for ADRD with cardiometabolic comorbidities in African Americans; leaves open validation before clinical use.
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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Pan et al. (2024) conducted an observational in Alzheimer's disease and related dementias (ADRD) and comorbid conditions (n=1,177). Single nucleotide polymorphisms (SNPs) was evaluated on Dual time-to-event outcomes for ADRD and a comorbid condition. Analysis identified 6 known and 8 novel single nucleotide polymorphisms significantly associated with the co-occurrence of ADRD and comorbid conditions such as congestive heart failure and cancer.
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