The power of representation: Statistical analysis of diversity in US Alzheimer's disease genetics data

• Published in: Alzheimer's & dementia : translational research & clinical interventions 2024-01, Vol.10 (1), p.e12462-n/a
• Main Authors: Xue, Diane, Blue, Elizabeth E., Conomos, Matthew P., Fohner, Alison E.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; ancestry; community‐based participatory research; diversity; ethnicity; genetics; race; representation; statistical power
• ISSN: 2352-8737; 2352-8737
• DOI: 10.1002/trc2.12462

INTRODUCTION Alzheimer's disease (AD) is a complex disease influenced by genetics and environment. More than 75 susceptibility loci have been linked to late‐onset AD, but most of these loci were discovered in genome‐wide association studies (GWAS) exclusive to non‐Hispanic White individuals. There are wide disparities in AD risk across racially stratified groups, and while these disparities are not due to genetic differences, underrepresentation in genetic research can further exacerbate and contribute to their persistence. We investigated the racial/ethnic representation of participants in United States (US)‐based AD genetics and the statistical implications of current representation. METHODS We compared racial/ethnic data of participants from array and sequencing studies in US AD genetics databases, including National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) and NIAGADS Data Sharing Service (dssNIAGADS), to AD and related dementia (ADRD) prevalence and mortality. We then simulated the statistical power of these datasets to identify risk variants from non‐White populations. RESULTS There is insufficient statistical power (probability