The Alzheimer’s Disease Sequencing Project Follow Up Study (ADSP‐FUS): increasing ethnic diversity in Alzheimer’s disease (AD) genetics research.

Abstract

AbstractBackgroundThe ADSP‐FUS is a National Institute on Aging (NIA) initiative focused on identifying genetic risk and protective variants for Alzheimer Disease (AD) by expanding the ADSP Discovery and Discovery Extension cohorts beyond non‐Hispanic Whites of European Ancestry (NHW‐EA). Given the lack of diversity in the ADSP, the ADSP‐FUS was designed to sequence existing ethnically diverse and unique cohorts. The upcoming phase for ADSP‐FUS, ADSP‐ FUS 2.0: The Diverse Population Initiative, focuses on Hispanic/Latino (HL), non‐Hispanic Black with African Ancestry (NHB‐AA), and Asian populations (e.g., the Asian cohort for Alzheimer’s disease). The ADSP‐FUS enables the utility of new discoveries for individuals from all populations.MethodADSP‐FUS cohorts consist of studies of AD, dementia, and age‐related conditions. Clinical classifications (AD, dementia, and cognitively intact) are assigned based on standard criteria and derived from clinical measures and history. Data dictionaries are curated for each cohort by the FUS clinical staff. The ADSP‐FUS initiatives intend to sequence over 100,000 individuals from diverse ancestries.Biospecimens are processed and DNA is prepared and allocated for whole genome sequencing (WGS) at designated NIA sequencing centers. All raw sequence data is transferred to the Genome Center for Alzheimer’s Disease (GCAD) for processing and harmonization following QC analysis at the University of Pennsylvania and University of Miami, resulting in analysis‐ready genotype and sequence data. All clinical, genotype and sequence data are housed at the NIA Genetics of Alzheimer Disease Data Storage Site (NIAGADS), which stores, manages, and distributes ASDP‐FUS data to AD researchers.ResultsOver 50,152 samples have been ascertained with ancestry groupings as follows: 10,166 NHB‐AA; 10,531 HL; 22,002 NHW‐EA (including 1,400 EOAD and 3,745 autopsy); 89 Amerindian; and 7,364 Asian (Korean and Indian) individuals. Currently, we have sequenced up to a total of 31,990 individuals.ConclusionThe ADSP‐FUS continues to identify shared and novel genetic risk factors for AD among diverse populations. This genomic resource is crucial to expanding our knowledge of potential genetic risk and protective variants for AD across all populations with the hope of developing new treatments for everyone.