The transferability of lipid-associated loci across African, Asian and European cohorts

Publication type

Journal Article

Published in

bioRxiv

Authors

Nikita Telkar, Theresa Reiker, Robin G. Walters, Kuang Lin, Deepti Gurdasani, Arthur Gilly, Lorraine Southam, Emmanouil Tsafantakis, Maria Karaleftheri, Janet Seeley, Anatoli Kamali, Gershim Asiki, Iona Y. Millwood, Huaidong Du, Yu Guo, Meena Kumari, George Dedoussis, Liming Li, Zhengming Chen, Manjinder S. Sandhu, Eleftheria Zeggini and Karoline Kuchenbaecker

Publication date

Summary

The under-representation of non-European samples in genome-wide association studies could ultimately restrict who benefits from medical advances through genomic science. Our aim was therefore to address the fundamental question whether causal variants for blood lipids are shared across populations. A polygenic score based on established LDL-cholesterol-associated loci from European discovery samples had consistent effects on serum levels in samples from the UK, Uganda and Greek population isolates (correlation coefficient r=0.23 to 0.28 per LDL standard deviation, p<1.9x10-14). Trans-ethnic genetic correlations between European ancestry, Chinese and Japanese cohorts did not differ significantly from 1 for HDL, LDL and triglycerides. In each study, >60% of major lipid loci displayed evidence of replication with one exception. There was evidence for an effect on serum levels in the Ugandan samples for only 10% of major triglyceride loci. The PRS was only weakly associated in this group (r=0.06, SE=0.013). We establish trans-ethnic colocalization as a method to distinguish shared from population-specific trait loci. Our results provide evidence for high levels of consistency of genetic associations for cholesterol biomarkers across populations. However, we also demonstrate that the degree of shared causal genetic architecture can be population-, trait- and locus-specific. Efforts to implement genetic risk prediction in clinical settings should account for this.

DOI

https://doi.org/10.1101/525170

Subjects

Medicine, Demography, Ethnic Groups, Health, Biology and Genetics

Notes

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