Leveraging putative enhancer-promoter interactions to investigate two-way epistasis in Type 2 Diabetes GWAS

Elisabetta Manduchi^1,2, Alessandra Chesi², Molly A. Hall¹, Struan F. A. Grant², Jason H. Moore^1,*

¹Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania
²Division of Human Genetics and Endocrinology, The Children's Hospital of Philadelphia
^*Corresponding author
Email: manduchi@pennmedicine.upenn.edu, chesia@email.chop.edu, hallma@mail.med.upenn.edu, grants@email.chop.edu, jhmoore@exchange.upenn.edu

Pacific Symposium on Biocomputing 23:548-558(2018)

© 2018 World Scientific
Open Access chapter published by World Scientific Publishing Company and distributed under the terms of the Creative Commons Attribution (CC BY) 4.0 License.

Abstract

We utilized evidence for enhancer-promoter interactions from functional genomics data in order to build biological filters to narrow down the search space for two-way Single Nucleotide Polymorphism (SNP) interactions in Type 2 Diabetes (T2D) Genome Wide Association Studies (GWAS). This has led us to the identification of a reproducible statistically significant SNP pair associated with T2D. As more functional genomics data are being generated that can help identify potentially interacting enhancer-promoter pairs in larger collection of tissues/cells, this approach has implications for investigation of epistasis from GWAS in general.