Polygenic transcriptome risk scores (PTRS) can improve portability of polygenic risk scores across ancestries

Yanyu Liang; Milton Pividori; Ani Manichaikul; Abraham A Palmer; Nancy J Cox; Heather E Wheeler; Hae Kyung Im

doi:10.1186/s13059-021-02591-w

Polygenic transcriptome risk scores (PTRS) can improve portability of polygenic risk scores across ancestries

Genome Biol. 2022 Jan 13;23(1):23. doi: 10.1186/s13059-021-02591-w.

Authors

Yanyu Liang¹, Milton Pividori², Ani Manichaikul³, Abraham A Palmer^{4

5}, Nancy J Cox⁶, Heather E Wheeler^{7

8

9}, Hae Kyung Im¹⁰

Affiliations

¹ Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, IL, USA. yanyul@uchicago.edu.
² Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, PA, USA.
³ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
⁴ Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
⁵ Institute for Genomic Medicine, University of California San Diego, San Diego, CA, USA.
⁶ Vanderbilt Genetic Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
⁷ Department of Biology, Loyola University Chicago, Chicago, IL, USA.
⁸ Program in Bioinformatics, Loyola University Chicago, Chicago, IL, USA.
⁹ Department of Public Health Sciences, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
¹⁰ Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, IL, USA. haky@uchicago.edu.

Abstract

Background: Polygenic risk scores (PRS) are valuable to translate the results of genome-wide association studies (GWAS) into clinical practice. To date, most GWAS have been based on individuals of European-ancestry leading to poor performance in populations of non-European ancestry.

Results: We introduce the polygenic transcriptome risk score (PTRS), which is based on predicted transcript levels (rather than SNPs), and explore the portability of PTRS across populations using UK Biobank data.

Conclusions: We show that PTRS has a significantly higher portability (Wilcoxon p=0.013) in the African-descent samples where the loss of performance is most acute with better performance than PRS when used in combination.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Genetic Predisposition to Disease
Genome-Wide Association Study*
Humans
Multifactorial Inheritance
Polymorphism, Single Nucleotide
Risk Factors
Transcriptome*

Abstract

Publication types

MeSH terms

Grants and funding