Genetics of Aging, Health, and Longevity: Focus on Regulatory Mechanisms and Functional Variants Connecting Aging and Alzheimer's Disease

The objective of this project is to find common regulatory and rare functional genetic variants involved in
both aging and Alzheimer’s disease (AD), and suggest new genetic targets for AD prevention. We plan to:
(i) evaluate collective effects of genetic interactions using newly developed in our group Interaction
Polygenic Risk Score (IPRS), allowing to integrate the additive and interaction effects of genes on AD and
aging traits, which presents significant methodological advantage; (ii) leverage the whole exome
sequencing data (WXS), to find rare functional variants associated with aging and AD; (iii) focus on genetic
regulators of translation that influence levels of proteins and provide connection between genes and phenotypes;
and (iv) explore biological pathways involved in aging and AD. For this, we will conduct only secondary analyses
of existing genetic and phenotypic data collected in the Alzheimer's Disease Sequencing Project (ADSP), as well as
in other studies, including Framingham Cohort (a.k.a., Framingham Heart Study (FHS)), Cardiovascular Health
Study (CHS), Alzheimer’s Disease Neuroimaging Initiative (ADNI), and UK Biobank. Current request refers to the ADSP.
The analyses will be performed using relevant statistical methods and software. The project does not involve any contact
with or participation of the real subjects.

The objective of this project is to significantly improve our understanding of the heterogeneity of Alzheimer’
s disease (AD) and common genetic mechanisms in aging and AD, and find new genetic targets for AD
prevention, with emphasis on regulatory and rare functional variants involved in both aging and AD. This
objective will be addressed by conducting secondary analyses of existing human data collected in
existing human studies, containing genetic and phenotypic information on thousands of individuals.