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The transferability of lipid loci across African, Asian and European cohorts
Robin G Walters,
Iona Y. Millwood,
Understanding Society Scientific Group,
Manjinder S Sandhu,
Posted 20 Jan 2019
bioRxiv DOI: 10.1101/525170
Posted 20 Jan 2019
The majority of genetic studies for cardiometabolic traits were based on samples with European ancestry. Our aim was to assess whether genetic variants associated with blood lipids, a major risk factor for CVD, are shared across different populations. We compared genetic associations with lipids between samples from Uganda (N=6,407), China (N=21,295), Japan (N=162,255), the UK (N=9,961) and Greece (N=3,586). Using simulations, we established trans-ethnic colocalization as a method to distinguish shared from population-specific trait loci. Genetic correlations for HDL, LDL and triglycerides 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 Greek population isolates (r=0.23-0.28, p<1.9x10-14). Overall, ~75% of the major lipid loci from European discovery studies displayed evidence of replication at p<10-3, 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 lipid loci that did not replicate in the Ugandan population had pleiotropic associations with BMI in European ancestry samples while none of the replicating loci did. While lipid associations were highly consistent across European and Asian populations, there was a lack of replication particularly for established triglyceride loci in the Ugandan population. These loci might affect lipids by modifying food intake or metabolism in an environment offering diets rich in certain nutrients. This suggests that gene-environment interactions could play an important role for the transferability of complex trait loci.
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