Genetic association studies using disease liabilities from deep neural networks.

ABSTRACT: The case-control study is a widely used method for investigating the genetic underpinnings of binary traits. However, long-term, prospective cohort studies often grapple with absent or evolving health-related outcomes. Here, we propose two methods, liability and meta, for conducting genome-wide association studies (GWASs) that leverage disease liabilities calculated from deep patient phenotyping. Analyzing 38 common traits in ∼300,000 UK Biobank participants, we identified an increased number of loci in comparison to the number identified by the conventional case-control approach, and there were high replication rates in larger external GWASs. Further analyses confirmed the disease specificity of the genetic architecture; the meta method demonstrated higher robustness when phenotypes were

SUBMITTER: Yang L 

PROVIDER: S-EPMC11948217 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature