Examining sex differences in pleiotropic effects for depression and cognition using polygenic and gene-region aggregation techniques

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Erin B. Ware, PhD, MPH

University of Michigan

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Lauren L. Schmitz, PhD

University of Wisconsin - Madison

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Arianna Gard, PhD

University of Michigan

Project Description:

Even after accounting for sex differences in life expectancy, we still see more American women living with Alzheimer’s disease than men. Both longitudinal studies and meta-analyses support the conclusion that depressive symptoms are associated with an increase of Alzheimer’s disease and its related dementias. We also see higher rates of depression among women compared to men. This project aims to connect the dots – we want to examine if depression-related outcomes and the underlying biological factors for both depressive phenotypes and cognition contribute to the sex differences we see in cognitive functioning in older ages.

Potential Impact:

One of the most exciting parts of this project lies in the use of newer statistical techniques to get at the root of our research question. We’re employing two statistical aggregation techniques—polygenic scores and sequence kernel association testing—to assess whether there are different relationships between depression and cognition genetics on cognition in later life, by sex, in the Health and Retirement Study. This research could have important implications for early identification of high-risk groups and could one day help lead to improvements in quality of life for those living with Alzheimer’s disease.

Next Steps:

If this project is successful, we hope to continue to bring in more collaborators in the RCCN to talk about how this work can be extended, replicated, and translated into practice.

The importance/value of RCCN funding for this collaborative research:

This project bridges expertise in population health, psychology, and genomics with research on Alzheimer’s disease and its related dementias. Funding from the RCCN has allowed us to foster a collaboration across NIA research centers for a project that otherwise would have been difficult to pull together as early career scientists.