FairPRS: adjusting for admixed populations in polygenic risk scores using invariant risk minimization

deep learning
genetics
statistics

Applying Invariant Risk Minimization (IRM) to debias ethnically-biased polygenic risk scores.

Authors
Affiliations

Diego Machado Reyes

Rensselaer Polytechnic Institute

Aritra Bose

IBM Research, Yorktown

Ehud Karavani

IBM Research, Israel

Laxmi Parida

IBM Research, Yorktown

Published

January 3, 2023

Doi
Abstract

Polygenic risk scores (PRS) are increasingly used to estimate the personal risk of a trait based on genetics. However, most genomic cohorts are of European populations, with a strong under-representation of non-European groups. Given that PRS poorly transport across racial groups, this has the potential to exacerbate health disparities if used in clinical care. Hence there is a need to generate PRS that perform comparably across ethnic groups. Borrowing from recent advancements in the domain adaption field of machine learning, we propose FairPRS - an Invariant Risk Minimization (IRM) approach for estimating fair PRS or debiasing a pre-computed PRS. We test our method on both a diverse set of synthetic data and real data from the UK Biobank. We show our method can create ancestry-invariant PRS distributions that are both racially unbiased and largely improve phenotype prediction. We hope that FairPRS will contribute to a fairer characterization of patients by genetics rather than by race.

Model overview

Citation

@inproceedings{reyes2023fairprs,
  title={FairPRS: adjusting for admixed populations in polygenic risk scores using invariant risk minimization},
  author={Reyes, Diego Machado and Bose, Aritra and Karavani, Ehud and Parida, Laxmi},
  booktitle={Pacific Symposium on Biocomputing},
  year={2023}
}