INFIMA leverages multi-omics model organism data to identify effector genes of human GWAS variants

Dong, C.; Simonett, S. P.; Shin, S.; Stapleton, D. S.; Schueler, K. L.; Churchill, G. A.; Lu, L.; Liu, X.; Jin, F.; Li, Y.; Attie, A. D.; Keller, M. P.; Keles, S.

doi:10.1101/2021.07.15.452422

bioRxiv · 10.1101/2021.07.15.452422

INFIMA leverages multi-omics model organism data to identify effector genes of human GWAS variants

Dong, C.·Simonett, S. P.·Shin, S.·Stapleton, D. S.·Schueler, K. L.·Churchill, G. A.·Lu, L.·Liu, X.·Jin, F.·Li, Y.·Attie, A. D.·Keller, M. P.·Keles, S.

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Abstract

Genome-wide association studies have revealed many non-coding variants associated with complex traits. However, model organism studies have largely remained as an untapped resource for unveiling the effector genes of non-coding variants. We develop INFIMA, Integrative Fine-Mapping, to pinpoint causal SNPs for Diversity Outbred (DO) mice eQTL by integrating founder mice multi-omics data including ATAC-seq, RNA-seq, footprinting, and in silico mutation analysis. We demonstrate INFIMAs superior performance compared to alternatives with human and mouse chromatin conformation capture datasets. We apply INFIMA to identify novel effector genes for GWAS variants associated with diabetes. The results of the application are available at http://www.statlab.wisc.edu/shiny/INFIMA/

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Dong, C., Simonett, S. P., Shin, S., Stapleton, D. S., Schueler, K. L., Churchill, G. A., Lu, L., Liu, X., Jin, F., Li, Y., Attie, A. D., Keller, M. P., Keles, S.. 2021-07-15. INFIMA leverages multi-omics model organism data to identify effector genes of human GWAS variants. https://doi.org/10.1101/2021.07.15.452422

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