BackgroundIdentifying genetic variants conferring resilience to Alzheimer's disease and related dementia (ADRD) may hold promise for developing therapeutics.ObjectiveTo determine genetic associations Show more
BackgroundIdentifying genetic variants conferring resilience to Alzheimer's disease and related dementia (ADRD) may hold promise for developing therapeutics.ObjectiveTo determine genetic associations with being dementia-free at age 85 (DF85).MethodsWe examined genetic associations, using whole genome sequencing data, with DF85 in three Trans-Omics for Precision Medicine cohorts and the Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium. We tested common variants individually and aggregation of rare (MAF ≤ 1%) coding and non-coding variants in DF85 participants (n = 3657) against individuals who were not DF85 (n = 20,010). We verified associations using a stricter control set who developed dementia before age 85 (n = 5552).ResultsWe observed an association at Show less
Alzheimer's disease and related dementias are influenced by genetic and environmental risk factors. We investigated the relationship between contextual exposures and cognitive outcomes, independent of Show more
Alzheimer's disease and related dementias are influenced by genetic and environmental risk factors. We investigated the relationship between contextual exposures and cognitive outcomes, independent of and in interaction with polygenic risk. Using the Multi-Ethnic Study of Atherosclerosis (N = 5687), we assessed the associations of contextual determinants representing the social, chemical, and built environment with incident dementia and late-life cognition using proportional hazards regression and generalized estimating equation models, then evaluated their joint effects stratified by genetic risk via Bayesian kernel machine regression. Neighborhood disadvantage was associated with higher dementia risk and poorer cognitive scores after adjusting for genetic risk and other individual-level covariates. Joint analysis of all contextual determinants indicated that more deleterious mixtures of contextual determinants are associated with lower late-life cognition among apolipoprotein E ɛ4 non-carriers with intermediate polygenic risk. Contextual determinants are associated with dementia and late-life cognition after adjusting for age, sex, education, and genetic risk. Show less
Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data fr Show more
Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals (P < 5 × 10 Show less
Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data fr Show more
Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals ( Show less