Genotyping NHATS DNA Samples: Laying the Foundation for ADRD Polygenic Scores

Johns Hopkins University, Baltimore MD

Investigators

Linked publications, trials & patents

Abstract

The National Health and Trends Study (NHATS) was launched to serve as a platform for research to understand how and why late life disability trends are shifting. The specific aims of NHATS are to (1) to promote scientific inquiry into late-life disability trends and dynamics, their antecedents and correlates, and disparities therein and (2) to advance study of the social and economic consequences of late-life disability for individuals, families, and society. NHATS provides a nationally representative sample of older adults and was developed specifically to enable analyses of both disability trends and trajectories. The study's design also includes oversamples of black individuals and persons at older ages in the population age 65 and older. Consistent with the objective of enabling research on disability trends and trajectories, in 2017, dried blood spots (DBS) were collected to implement assays that may influence disability progression and for use in future genetic research. This application in response to NIA notice NOT-AG-18-008, provides the opportunity to genotype DNA from the NHATS DBS samples to set the stage to construct an AD polygenic score for a well-defined NHATS Alzheimer's disease and related dementia (ADRD) phenotype, as well as development of polygenic scores for other phenotypes. The specific aims of this supplement are: 1) To conduct genotyping of DNA for all 2017 NHATS DBS participants using a high-quality, cost-effective array with multiethnic genome- wide content that is designed for population-scale genetic studies and 2) To implement a standard Quality Control (QC) protocol used at the Johns Hopkins McKusick-Nathans Institute of Genetic Medicine on the raw genotyped data, to submit the data and QC information to dbGaP, and to transmit the data to the University of Michigan in preparation for construction of AD and other polygenic scores. Genotyping DNA for NHATS is a key step that makes possible development of polygenic scores, thus extending opportunities for NHATS analyses into new areas. We plan to harmonize the construction of the NHATS polygenic scores, including for AD, with those developed for the Health and Retirement Study (Ware et al. 2017), and to distribute these under established NHATS restricted data procedures to the NHATS user community.