Expanding Polygenic Risk Scores to Include Automatic Genotype Encodings and Gene-gene Interactions

Trang T. Le, Hoyt Gong, Patryk Orzechowski, Elisabetta Manduchi, Jason H. Moore

2020

Abstract

Polygenic Risk Scores (PRS) are aggregation of genetic risk factors of specific diseases and have been successfully used to identify groups of individuals who are more susceptible to those diseases. While several studies have focused on identifying the correct genetic variants to include in PRS, most existing statistical models focus on the marginal effect of the variants on the phenotypic outcome but do not account for the effect of gene-gene interactions. Here, we propose a novel calculation of the risk score that expands beyond marginal effect of individual variants on the outcome. The Multilocus Risk Score (MRS) method effectively selects alternative genotype encodings and captures epistatic gene-gene interactions by utilizing an efficient implementation of the model-based Multifactor Dimensionality Reduction technique. On a diverse collection of simulated datasets, MRS outperforms the standard PRS in the majority of the cases, especially when at least two-way interactions between the variants are present. Our findings suggest that models incorporating epistatic interactions are necessary and will yield more accurate and effective risk profiling.

Paper Citation

in Harvard Style

Le T., Gong H., Orzechowski P., Manduchi E. and Moore J. (2020). Expanding Polygenic Risk Scores to Include Automatic Genotype Encodings and Gene-gene Interactions. In Proceedings of the 13th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2020) - Volume 3: BIOINFORMATICS; ISBN 978-989-758-398-8, SciTePress, pages 79-84. DOI: 10.5220/0008869700790084

in Bibtex Style

@conference{bioinformatics20,
author={Trang T. Le and Hoyt Gong and Patryk Orzechowski and Elisabetta Manduchi and Jason H. Moore},
title={Expanding Polygenic Risk Scores to Include Automatic Genotype Encodings and Gene-gene Interactions},
booktitle={Proceedings of the 13th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2020) - Volume 3: BIOINFORMATICS},
year={2020},
pages={79-84},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0008869700790084},
isbn={978-989-758-398-8},
}

in EndNote Style

TY - CONF

JO - Proceedings of the 13th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2020) - Volume 3: BIOINFORMATICS
TI - Expanding Polygenic Risk Scores to Include Automatic Genotype Encodings and Gene-gene Interactions
SN - 978-989-758-398-8
AU - Le T.
AU - Gong H.
AU - Orzechowski P.
AU - Manduchi E.
AU - Moore J.
PY - 2020
SP - 79
EP - 84
DO - 10.5220/0008869700790084
PB - SciTePress