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Trans-ethnic polygenic risk scores for body mass index: An international hundred K+ cohorts consortium study.

Published version
Peer-reviewed

Repository DOI


Type

Article

Change log

Authors

Connolly, John J 
Kraft, Peter 
Long, Jirong 
Pereira, Alexandre 

Abstract

BACKGROUND: While polygenic risk scores hold significant promise in estimating an individual's risk of developing a complex trait such as obesity, their application in the clinic has, to date, been limited by a lack of data from non-European populations. As a collaboration model of the International Hundred K+ Cohorts Consortium (IHCC), we endeavored to develop a globally applicable trans-ethnic PRS for body mass index (BMI) through this relatively new international effort. METHODS: The polygenic risk score (PRS) model was developed, trained and tested at the Center for Applied Genomics (CAG) of The Children's Hospital of Philadelphia (CHOP) based on a BMI meta-analysis from the GIANT consortium. The validated PRS models were subsequently disseminated to the participating sites. Scores were generated by each site locally on their cohorts and summary statistics returned to CAG for final analysis. RESULTS: We show that in the absence of a well powered trans-ethnic GWAS from which to derive marker SNPs and effect estimates for PRS, trans-ethnic scores can be generated from European ancestry GWAS using Bayesian approaches such as LDpred, by adjusting the summary statistics using trans-ethnic linkage disequilibrium reference panels. The ported trans-ethnic scores outperform population specific-PRS across all non-European ancestry populations investigated including East Asians and three-way admixed Brazilian cohort. CONCLUSIONS: Here we show that for a truly polygenic trait such as BMI adjusting the summary statistics of a well powered European ancestry study using trans-ethnic LD reference results in a score that is predictive across a range of ancestries including East Asians and three-way admixed Brazilians.

Description

Funder: Economic and Social Research Council


Funder: Wellcome Trust


Funder: Chief Scientist Office


Funder: NIHR BioResource

Keywords

body mass index, obesity, polygenic risk score, population admixture, trans-ethnic, Child, Humans, Bayes Theorem, Body Mass Index, Genome-Wide Association Study, Multifactorial Inheritance, Risk Factors

Journal Title

Clin Transl Med

Conference Name

Journal ISSN

2001-1326
2001-1326

Volume Title

13

Publisher

Wiley
Sponsorship
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
British Heart Foundation (RG/18/13/33946)
National Institute for Health and Care Research (IS-BRC-1215-20014)