The WHICAP WES study consists of a multi-ethnic cohort of 4,100 individuals followed over several years. Participants were community-living Medicare recipients 65 years and older recruited from northern Manhattan to participate in the Washington Heights-Inwood Columbia Aging Project. Potential participants were identified based on residence in US Census tracts within the study catchment area. Recruitment occurred in three waves: 1992 (N = 2126), 1999 (N = 2174), and 2009 (N = 2128). Participants completed a baseline assessment and were followed up at 18- to 24-month intervals for up to 25 years. During each session, participants were administered a neuropsychological battery and asked about their general health, functional ability, and medical history and were re‐consented for sharing of genetic information and autopsy. Evaluations were conducted in English or Spanish, based on language preference. The cohort participants were non-demented initially, 65 years of age or older, and comprised of non‐Hispanic whites, African Americans, and Caribbean Hispanics from the Dominican Republic. A consensus diagnosis was derived for each participant by experienced clinicians based on NINCDS‐ADRDA criteria for possible, probable, or definite AD, or moderate or high likelihood of neuropathological criteria of AD.

Every individual with whole‐exome sequencing has at least a baseline and one follow‐up assessment and examination, and for those who have died, the presence or absence of dementia was determined using a brief, validated telephone interview with participant informants: the Dementia Questionnaire (DQ) and the Telephone Interview of Cognitive Status (TICS). 4,100 exome sequenced WHICAP individuals were designated with case or control status. Whole‐exome sequencing of the WHICAP cohort was performed at Columbia University.

Columbia WHICAP samples were sequenced at IGM- Columbia University on the HiSeq2000 machine.  1130 African American, 1829 Hispanic and 896 Caucasian samples were sequenced using the Roche SeqCap EZ Exome Probes v3.0 Target Enrichment Probes. BAM files from hg38 build were sent to GCAD for processing on the VCPA1.1 pipeline. 3170 passed sequencing metrics and quality control.