Genomewide analysis of Episodic Memory trajectories in The Mexican Health and Aging Study (MHAS)

Abstract

AbstractBackgroundGenetic characterization of age‐related memory changes can help identify population subgroups at‐risk of memory decline and dementia. The majority of genetic studies examining memory trajectories in old age have used data from non‐Hispanic White populations. To our knowledge, there are no reports of genetic factors underlying memory function over time in the Mexican population.MethodUsing a previously described latent curve model approach, we estimated episodic memory trajectories in a longitudinal sample from the Mexican Health and Aging Study. We conducted GWAS analyses in a sub‐sample of 6,343 participants. Analyses were stratified by memory stability (Stables, n = 4,437) and APOE status. Three independent cohorts were used for replication purposes: two Non‐Hispanic White samples from the Alzheimer’s Disease Genetic Consortium and the Religious Orders Study, and a Caribbean‐Hispanic sample from the Washington Heights Inwood Community Aging Project.ResultThe strongest genome‐wide significant association was found for an intronic variant in the NR2F1‐AS1 gene (rs555528825, p = 1.8×10−9) among APOE non‐E4 carriers in the “Stables” group. NR2F1 gene is an evolutionarily conserved long non‐coding RNA that enhances neuronal cell maturation and regulates transcription of neuronal genes. SNP variants located less than 50Kb apart from the identified signal showed also nominally significant associations in the three replication datasets (p = 3.9×10−4, p = 1.8×10−4, and p = 0.006 respectively). Additional replication efforts using the UK biobank recourse are ongoing.ConclusionOur study nominates novel genetic variants associated with longitudinal changes in episodic memory performance using data from the Mexican Health and Aging Study, a representative and comprehensive longitudinal study that includes genetic data on a sub‐sample of participants 50 years and older.