Integrative analysis of the genome, transcriptome, and proteome identifies causal mechanisms of complex traits.

Okamoto, J.; Yin, X.; Ryan, B.; Chiou, J.; Luca, F.; Pique-Regi, R.; Im, H. K.; Morrison, J.; Burant, C.; Fauman, E.; Laakso, M.; Boehnke, M.; Wen, X.

doi:10.1101/2024.03.28.587202

bioRxiv · 10.1101/2024.03.28.587202

Integrative analysis of the genome, transcriptome, and proteome identifies causal mechanisms of complex traits.

Okamoto, J.·Yin, X.·Ryan, B.·Chiou, J.·Luca, F.·Pique-Regi, R.·Im, H. K.·Morrison, J.·Burant, C.·Fauman, E.·Laakso, M.·Boehnke, M.·Wen, X.

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Abstract

We present multi-integration of transcriptome-wide association studies and colocalization (Multi-INTACT), an algorithm that models multiple gene products (e.g. encoded RNA transcript and protein levels) to implicate causal genes and relevant gene products. In simulations, Multi-INTACT achieves higher power than existing methods, maintains calibrated false discovery rates, and detects the true causal gene product(s). We apply Multi-INTACT to GWAS on 1,408 metabolites, integrating the GTEx expression and UK Biobank protein QTL datasets. Multi-INTACT infers 52% to 109% more metabolite causal genes than protein-alone or expression-alone analyses and indicates both gene products are relevant for most gene nominations.

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Okamoto, J., Yin, X., Ryan, B., Chiou, J., Luca, F., Pique-Regi, R., Im, H. K., Morrison, J., Burant, C., Fauman, E., Laakso, M., Boehnke, M., Wen, X.. 2024-03-31. Integrative analysis of the genome, transcriptome, and proteome identifies causal mechanisms of complex traits.. https://doi.org/10.1101/2024.03.28.587202

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