Combining MRI and genetic data in the Tohoku Medical Megabank Organization cohort study for innovative Alzheimer’s disease research

Abstract

AbstractBackgroundThe Tohoku Medical Megabank Organization (ToMMo) is a prospective genome cohort study and biobank established in 2012 in Northern Japan’s Miyagi Prefecture following the Great East Japan Earthquake and Tsunami. ToMMo has enrolled 120,000 healthy male and female adults aged over 20, plus 30,000 children in a longitudinal study designed to identify diverse biological, psychological, and lifestyle characteristics associated with mainly common diseases and support additional innovative research. Baseline information includes brain MRI, genetic data, physiological measurements, several cognitive and psychological screening tests, and health/lifestyle assessments. Alzheimer’s disease (AD) is a key research focus; goals include using MRI, genomic and other data in combination to identify predictive biomarkers. This communication reports initial progress.MethodMRI: MP‐RAGE, PCASL, FLAIR and DTI sequences were performed. Following quality checks and pre‐processing, Freesurfer (2.1.0) was used with the Destrieux or Desikan‐Killiany atlas to parcellate multiple anatomical brain regions and derive cortical thickness data. The digitized data were archived; raw data was preserved. Genetics: whole genome sequencing (WGS) and/or DNA array data were obtained for participants; apolipoprotein E (APOE) genotype was identified. Blood, urine, stool, saliva and dental plaque samples were collected and stored for biomarker identification and other studies.ResultUsable MRI data exist for >12,000 participants (4,000 for FLAIR); approximately half the scans are of participants aged ≥50 (see Table). The quality exclusion rate was <5%. WGS and DNA array data have so far been prepared for 800 participants who had MRI scans; APOE genotype information exists for all participants with MRI scans. The MRI and genetic data, plus demographic, cognitive screening and relevant health data are currently being readied for use in combination to identify valuable biomarkers, e.g., those predicting incipient cognitive impairment in preclinical AD. The frequency of major known AD risk alleles in the ToMMo sample will also be determined and compared to that in external GWAS studies.ConclusionToMMo’s MRI, WGS/DNA array, biospecimen repository and other data represent a powerful resource for AD research. Specifically, the combination of MRI and genetic data will support unique disease progression analyses and investigations to elucidate AD pathophysiology.