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

Nikita Telkar, Theresa Reiker, Robin G. Walters, Kuang Lin, Anders Eriksson, Deepti Gurdasani, Arthur Gilly, Lorraine Southam, Emmanouil Tsafantakis, Maria Karaleftheri, Janet Seeley, Anatoli Kamali, Gershim Asiki, Iona Y. Millwood, Michael Holmes, HuaidongDu, Yu Guo, Understanding Society Scientific Group, Meena Kumari, George Dedoussis, Liming Li, Zhengming Chen, Manjinder S. Sandhu, Eleftheria Zeggini, Karoline Kuchenbaecker

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Apr 09, 2019
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Received Date: 26th March 19

Most genome-wide association studies are based on samples of European descent. Our aim was to assess whether the genetic determinants of blood lipids, a major cardiovascular risk factor, are shared across different populations. 
Genetic correlations for lipids between European ancestry and Asian cohorts were close to 1. 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 Greece (r=0.23-0.28, p<1.9x10-14). Overall, ~75% of the major lipid loci from European discovery studies displayed evidence of replication, except triglyceride loci in the Ugandan samples of which only 10% replicated. Specific replicating loci were identified using trans-ethnic colocalization. Ten of the fourteen loci that did not replicate in the Ugandan samples had pleiotropic associations with BMI in European data while none of the replicating loci did. The non-replicating loci might affect lipids by modifying food intake only in environments offering diets rich in certain nutrients, which suggests an important role for gene-environment interactions. Incorporating this into genetic risk prediction could help ensure that the health benefits of precision medicine are widely shared within and across populations.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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