Alzheimer's Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans

Abstract

The role of the Alzheimer's Disease Neuroimaging Initiative Genetics Core is to facilitate the investigation of genetic influences on disease onset and trajectory as reflected in structural, functional, and molecular imaging changes; fluid biomarkers; and cognitive status. Major goals include (1) blood sample processing, genotyping, and dissemination, (2) genome-wide association studies (GWAS) of longitudinal phenotypic data, and (3) providing a central resource, point of contact and planning group for genetics within the Alzheimer's Disease Neuroimaging Initiative. Genome-wide array data have been publicly released and updated, and several neuroimaging GWAS have recently been reported examining baseline magnetic resonance imaging measures as quantitative phenotypes. Other preliminary investigations include copy number variation in mild cognitive impairment and Alzheimer's disease and GWAS of baseline cerebrospinal fluid biomarkers and longitudinal changes on magnetic resonance imaging. Blood collection for RNA studies is a new direction. Genetic studies of longitudinal phenotypes hold promise for elucidating disease mechanisms and risk, development of therapeutic strategies, and refining selection criteria for clinical trials.

Fig. 1

Manhattan plot for percent change in hippocampal volume over 1 year.

Fig. 2

Manhattan plot for percent change in hippocampal grey matter density over 1 year.

Fig. 3

Mean (±SE) bilateral entorhinal cortex thickness on baseline MRI as a function of PICALM (rs3851179) genotype and diagnosis group. Participants who had a baseline diagnosis of MCI but converted to probable AD within a year are included with the AD at baseline group. The MCI-stable group included participants with a stable MCI diagnosis over 1 year. See text for details.