Biology subjects

Ware, E. B.

Publications and source records attributed to Ware, E. B..

3 recordsLinked to original sources

bioRxiv2025

Identification of chemicals targeting dementia genes and pathways using the Comparative Toxicogenomics Database

IntroductionDementia is a public health challenge and exposures likely contribute to risk, though many have not been evaluated. We screened chemicals for enrichment with dementia genes and related pathways. MethodsWe obtained gene lists from the Comparative Toxicogenomics Database for 1,008 chemicals and nine dementia-related pathways (e.g., Alzheimers disease, tauopathies). We tested pairwise chemical-dementia gene enrichment using Fishers exact tests and proportional reporting ratios (PRR), accounting for multiple comparisons with false discovery rate (FDR<1x10-6). ResultsOf the chemicals tested, 742 (73.6%) were enriched for at least one dementia pathway and 15 with all nine pathways, including benzo(a)pyrene, ethanol, paraquat, and particulate matter. We observed 295 chemicals enriched for Alzheimers disease, including sodium arsenite (PRR = 57.9) and 305 enriched for tauopathies, including bisphenol A (PRR=37.7). DiscussionWe identified chemicals enriched for dementia pathways, suggesting broad classes of chemicals contribute to dementia.

genomics↗

bioRxiv2019

Assessing the Structure and Specificity of Polygenic Scores for Psychiatric Disorders in a Population-based Cohort of Older Adults

Although psychiatric phenotypes are hypothesized to organize into a two-factor internalizing - externalizing structure, few studies have evaluated the structure of psychopathology in older adults, nor explored whether genome-wide polygenic scores (PGSs) are associated with psychopathology in a domain-specific manner. We used data from 6,216 individuals of European ancestry from the Health and Retirement Study, a large population-based sample of older adults in the United States. Confirmatory factor analyses were applied to validated measures of psychopathology and PGSs were derived from well-powered GWAS. Genomic SEM was implemented to construct latent PGSs for internalizing, externalizing, and general psychopathology. Phenotypically, the data were best characterized by a single general factor of psychopathology, a factor structure that was replicated across genders and age groups. Although externalizing PGSs (cannabis use, antisocial behavior, alcohol dependence, ADHD) were not associated with any phenotypes, PGSs for MDD, neuroticism, and anxiety disorders were associated with both internalizing and externalizing phenotypes. Moreover, the latent internalizing PGS and the latent one-factor PGS, derived using weights from Genomic SEM, explained 1% more variance in the general factor of psychopathology than any of the individual PGSs. Results support the following conclusions: genetic risk factors for and phenotypic markers of psychiatric disorders are transdiagnostic in European ancestries, GWAS-derived PGSs fail to capture genetic variation associated with disease specificity in European ancestries, and blunt phenotypic measurement in GWAS may preclude our ability to evaluate the structure and specificity of genetic contributions to psychiatric disorders.

genomics↗

bioRxiv2017

Heterogeneity in polygenic scores for common human traits

Introduction Introduction Results Discussion Materials and Methods Conflict of Interest References Genome-wide association studies (GWAS) on a wide range of important human traits have identified hundreds of variants in multi-cohort meta-analyses that have highly significant associations (p<5 x10-8) that replicate across studies. However, the identified genetic variants, or single nucleotide polymorphisms (SNPs), generally explain a very small fraction of variability in the trait of interest. Moreover, for most behavioral and health scientists, the use of such massive and complex genetic data is unwieldy. In response to the desire to harness genome-wide information, use of polygenic scores (PGSs), also known as \"genetic risk scores\", has grown rapidly in the social, behavioral, and health sciences rec ...

genetics↗