GWAS of Working Memory

GWAS of the RDoC Cognitive Systems Domain: Modeling the Latent Genetic Architecture of Working Memory

Grant No. (PI): R03 MH123787-01

  • Dates of Award: 06/10/2020-06/09/2022
  • Agency: National Institute of Mental Health (NIMH)
  • Percent Effort: 40


This two-year study will use existing GWAS data from COGENT to investigate the latent molecular genetic architecture of working memory. Working memory is a core Construct of the RDoC Cognitive Systems Domain, defined as the active maintenance and flexible updating of goal/task relevant information in a form that has limited capacity and resists interference. Limited working memory capacity is a fundamental aspect of the cognitive impairments prevalent in many neuropsychiatric disorders. Most of the variability underlying differences in general working memory capacity can be traced back to inherited genetic factors. However, exactly how our DNA shapes the working memory system has yet to be established. As such, our objective is to identify the spectrum of genome-wide allelic variation underlying working memory – from individual loci to genes to polygenic risk scores to functional biological pathways – determined to be causal, not merely correlational, in relation to working memory performance. Role: PI Total Direct Costs: $165,000

Joey Trampush, PhD
Della Martin Assistant Professor of Psychiatry and the Behavioral Sciences

Developmental Neuropsychologist & Geneticist | Psychiatry & Behavioral Sciences | Keck Medicine of USC


General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16– 102) and find 148 genome-wide significant independent loci (P textless 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.