Causal Inference Methods to Integrate Omics and Complex Traits

Major biotechnological advances have facilitated a tremendous boost to the collection of (gen-/transcript-/prote-/methyl-/metabol-)omics data in very large sample sizes worldwide. Coordinated efforts have yielded a deluge of studies associating diseases with genetic markers (genome-wide association studies) or with molecular phenotypes. Whereas omics-disease associations have led to biologically meaningful and coherent mechanisms, the identified (non-germline) disease biomarkers may simply be correlates or consequences of the explored diseases. To move beyond this realm, Mendelian randomization provides a principled framework to integrate information on omics- and disease-associated genetic variants to pinpoint molecular traits causally driving disease development. In this review, we show the latest advances in this field, flag up key challenges for the future, and propose potential solutions.

Automated summary

The advancement in biotechnology has greatly facilitated the collection of omics data in large sample sizes worldwide. Studies associating diseases with genetic markers have led to biologically meaningful mechanisms, but identifying disease biomarkers may be just correlates of diseases. Mendelian randomization offers a framework to integrate omics and disease-associated genetic variants to pinpoint molecular traits driving disease development.