NG00034 – ACT and Genetic Differences GWAS

The Adult Changes in Thought (ACT) study is a longitudinal prospective cohort study that
began in 1994. Participants are randomly selected from Seattle area members of Group
Health aged 65 years or older. Participants are cognitively intact at study enrollment,
defined operationally as a CASI (Cognitive Abilities Screening Instrument) score of >85 or
consensus diagnosis of “not demented” following comprehensive neurological and
neuropsychological assessment. Incident cases of dementia are identified with the same 2-
stage sampling scheme, where all participants with CASI scores <86 are evaluated with a
comprehensive neurological and neuropsychological assessment, and all results are
considered at a consensus conference. While ACT is continually enrolling subjects, Genetic
Differences has completed enrollment.
Genetic Differences (GenDiff) was an epidemiologic case-control study. Cases were newly
recognized (i.e., “incident”) “Probable AD” (McKhann criteria NINCDS-ADRDA). Subjects
were discovered and diagnosed by the Alzheimer’s Disease Patient Registry from a
community-based HMO. Controls were selected at random from the same HMO, without
cognitive impairment, and frequency matched for age and sex. They were also cognitively
screened and followed. Genetic Differences was funded through R01 AG007584.
This SNP array dataset, ACT and GenDiff GWAS, was used by the Alzheimer’s Disease
Genetics Consortium (ADGC) to identify genes associated with an increased risk of
developing Alzheimer’s disease. Provided here, are the PLINK genotype files that have
undergone ADGC quality control procedures, imputation files (.bgen format) generated
using the TOPMED r2 reference panel.