A phenome‐wide association study of polygenic scores for attention deficit hyperactivity disorder across two genetic ancestries in electronic health record data
Year: 2022
Type: article
Study design: Observational Study
Abstract: Testing the association between genetic scores for Attention Deficit Hyperactivity Disorder (ADHD) and health conditions, can help us better understand its complex etiology. Electronic health records linked to genetic data provide an opportunity to test whether genetic scores for ADHD correlate with ADHD and additional health outcomes in a health care context across different age groups. We generated polygenic scores (ADHD‐PGS) trained on summary statistics from the latest genome‐wide association study of ADHD (N = 55,374) and applied them to genome‐wide data from 12,383 unrelated individuals of African‐American ancestry and 66,378 unrelated individuals of European ancestry from the Vanderbilt Biobank. Overall, only Tobacco use disorder (TUD) was associated with ADHD‐PGS in the African‐American ancestry group (Odds ratio [95% confidence intervals] = 1.23[1.16–1.31], p = 9.3 × 10−09). Eighty‐six phenotypes were associated with ADHD‐PGS in the European ancestry individuals, including ADHD (OR[95%CIs] = 1.22[1.16–1.29], p = 3.6 × 10−10), and TUD (OR[95%CIs] = 1.22[1.19–1.25], p = 2.8 × 10−46). We then stratified outcomes by age (ages 0–11, 12–18, 19–25, 26–40, 41–60, and 61–100). Our results suggest that ADHD polygenic scores are associated with ADHD diagnoses early in life and with an increasing number of health conditions throughout the lifespan (even in the absence of ADHD diagnosis). This study reinforces the utility of applying trait‐specific PGSs to biobank data, and performing exploratory sensitivity analyses, to probe relationships among clinical conditions.
DOI: 10.1002/ajmg.b.32911
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,450
Funders: National Institutes of Health, Institute for Clinical and Translational Research, University of Wisconsin, Madison, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1182793083, Pharmacogenomics of Arrhythmia Therapy, Understanding the genetic risk underlying racial disparities in uterine fibroids, G2265622010, G2714998049, Improving Prediction of Drug Action, Mental health and chronic disease: A psycheMERGE investigation into the shared biology underlying psychiatric disorders and their physical comorbidities, G3804672761, Automated Storage and Retrieval of Biological Systems, Overall: Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at Vanderbilt, G5351519051, G5366963641, G563474107, G5721030143, G5868276417, Genetic Epidemiology of Multiple Sclerosis, G6001799246, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, G6775789183, VESPA: Vanderbilt Electronic Systems for Pharmacogenomic Assessment, G7038568617, G7653134492, The Vanderbilt Institute for Clinical and Translational Research (VICTR), G7903062031, Vanderbilt Genome Electronic Records Project, PsycheMERGE: Leveraging electronic health records and genomics for mental health research, Discovering Biology for Neuropsychiatric Diseases Through Omics Studies on Comorbidities, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), G887695823, Vanderbilt Institute for Clinical and Translational Research (VICTR), G952591774
OpenAlex ID: W4285590743