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Explaining the genetic causality for complex diseases via deep association kernel learning

Bao, F.; Deng, Y.; Du, M.; Ren, Z.; Wan, S.; Xin, J.; Chen, F.; Christiani, D. C.; Wang, M.; Dai, Q.

2019-12-25 bioinformatics
10.1101/2019.12.17.879866 bioRxiv
Show abstract

The genetic effect explains the causality from genetic mutation to the development of complex diseases. Existing genome-wide association study (GWAS) approaches are always built under a linear assumption, restricting their generalization in dissecting complicated causality such as the recessive genetic effect. Therefore, a sophisticated and general GWAS model that can work with different types of genetic effects is highly desired. Here, we introduce a Deep Association Kernel learning (DAK) model to enable automatic causal genotype encoding for GWAS at pathway level. DAK can detect both common and rare variants with complicated genetic effects that existing approaches fail. When applied to real-world GWAS data, our approach discovered potential casual pathways that could be explained by alternative biological studies.

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