Genetic studies of Alzheimer disease have focused on the clinical or pathologic diagnosis as the primary outcome, but little is known about the genetic basis of the preclinical phase of the disease. The objective of this study was to examine the underlying genetic basis for brain amyloidosis in the preclinical phase of Alzheimer disease.

Genome-wide association studies of positron emission tomographic (PET) imaging amyloid levels, followed by a meta-analysis, were conducted using genetic and imaging data acquired from 6 multicenter cohort studies of healthy older individuals: the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease Study, the Berkeley Aging Cohort Study, the Wisconsin Registry for Alzheimer’s Prevention, the Biomarkers of Cognitive Decline Among Normal Individuals cohort, the Baltimore Longitudinal Study of Aging, and the Alzheimer Disease Neuroimaging Initiative, which included Alzheimer disease and mild cognitive impairment. Participants older than 50 years with amyloid PET imaging data and DNA from the 6 cohorts were included. The largest cohort, the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease Study (n = 3154), was the PET screening cohort used for a secondary prevention trial designed to slow cognitive decline associated with brain amyloidosis. Six smaller, longitudinal cohort studies (n = 1160) provided additional amyloid PET imaging data with existing genetic data.