Genetics of deep-learning-derived neuroimaging endophenotypes for Alzheimer's Disease

Alzheimer’s disease (AD) affects 5.6 million Americans over the age of 65 and exacts tremendous and increasing demands on patients, caregivers, and healthcare resources. Our current understanding of the biology and pathophysiology of AD is still limited, hindering advances in the development of therapeutic and preventive strategies. Existing genetic studies of AD have some success but these explain only a fraction of the overall disease risk, suggesting opportunities for additional discoveries. The proposed project will leverage existing neuroimaging and genetic data resources from the UK Biobank, the Alzheimer’s Disease Sequencing Project (ADSP), the Alzheimer’s Disease Neuroimaging Initiative (ADNI), and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and will be conducted by a multidisciplinary team of investigators. We will derive AD endophenotypes from neuroimaging data in the UK Biobank using deep learning (DL). We will identify novel genetic loci associated with DL-derived imaging endophenotypes and optimize the co-heritability of these endophenotypes with AD-related phenotypes using UK Biobank genetic data. We will leverage resources and collaborations with AD Consortia and the power of DL-derived neuroimaging endophenotypes to identify novel genes for Alzheimer’s Disease and AD-related traits. Also, we will develop DL-based neuroimaging harmonization and imputation methods and distribute implementation software to the research community. We expect to discover new genes relevant to AD which may leads to understanding of molecular basis of AD and potential new treatment.

Alzheimer’s disease (AD) exacts a tremendous burden on patients, caregivers, and healthcare resources. Our current understanding of the biology of AD is still limited, hindering advances in the development of treatment and prevention. Existing genetic studies of AD have some success but more studies are needed. The proposed project will leverage existing neuroimaging and genetic data resources from the UK Biobank, the Alzheimer’s Disease Sequencing Project (ADSP) and other consortia and will be conducted by a multidisciplinary team of investigators. We will derive new AD relevant intermediate phenotypes from neuroimaging data using deep learning (DL), an AI approach. We will identify novel genetic loci associated with these phenotypes. Also, we will develop imaging harmonization and imputation methods and distribute implementation software to the research community. We expect to discover new genes relevant to AD which may leads to understanding of molecular basis of AD and potential new treatment.