Abstract 500: Assessing the Impact of Cardiovascular Disease-Related Genetic Variation on Clinical Cognitive Impairment
Introduction: “Cognitive impairment, no dementia” (CIND) is a prodromal stage of cognitive decline which marks the onset of dementia and is due most commonly to 1) Alzheimer disease (AD) or 2) vascular dysfunction. In order to assess the genetic component of CIND susceptibility, we investigated cardiovascular disease (CVD) and AD-associated genetic variation in CIND patients, hypothesizing that the genetic variation affecting CVD and AD susceptibility is also associated with CIND susceptibility. Methods: Our study cohort was taken from the Canadian Study of Health and Aging (CSHA) and was comprised of patients >65 years old with CIND (n=274) and matched normal controls (n=301). We genotyped ∼200,000 CVD-related SNPs using the Cardio-Metabochip genotyping array (Illumina). We also genotyped a panel of the top 11 AD-associated single nucleotide polymorphisms (SNPs) and APOE isotype. We tested for association between CIND status and genotypes using a logistic regression model adjusted for appropriate covariates. Genetic risk scores (GRSs) evaluated associations between CIND status and the accumulation of multiple genetic markers. Results: From our Cardio-Metabochip analysis, we identified 5 novel CIND susceptibility loci, with rs16901621 in FLJ22536 as our most significantly associated SNP (P=1.05E-06, OR=2.51, 95%CI=1.73-3.63). APOE ε4 isotype was modestly associated with CIND status (P<0.05), while AD SNP risk alleles were not associated (P>0.1). Conclusion: Using a high-throughput CVD microarray, we found novel genetic markers for CIND approaching genome-wide levels of significance. In contrast, known genetic markers for AD, such as APOE ε4 showed only modest associations in this cohort. Follow-up of variants in a CSHA replication cohort (n=370) is currently underway.
- © 2012 by American Heart Association, Inc.