Complex Genetic Interactions in AD

Alzheimer's disease (AD) is likely influenced by the interaction of many genetic and environmental factors, some of which may act by influencing brain gene expression.

The lab previously conducted an expression genome-wide association study (eGWAS) for approximately 200 AD participants and approximately 200 participants with other non-AD pathologies using samples from the temporal cortex and cerebellum of postmortem brain tissue to identify genetic variants that influence brain gene expression. However, the single nucleotide polymorphism (SNP) and single phenotype approach employed in GWAS research is likely an oversimplification of the complex biological interactions that take place in an organism. Gene (or SNP) interactions, known as epistasis, allow for the study of interaction effects of pairs of SNPs on a given phenotype. This research can uncover novel genetic factors that influence the diseases and phenotypes evaluated.

In this study the team will leverage existing brain eGWAS data to identify pairs of SNPs that associate with brain gene expression measures. The goal is to identify additional genetic factors that might influence Alzheimer's disease risk through alterations in gene expression.

The analysis of epistatic effects in large studies, such as this one, requires powerful computational resources. For this project the team has collaborated with researchers at the University of Illinois at Urbana-Champaign to perform these analyses. This is done using the unique petascale computational resources available at the National Center for Supercomputing Applications.