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

Karoline Kuchenbaecker ORCID logo; Nikita Telkar; Theresa Reiker; Robin G Walters ORCID logo; Kuang Lin; Anders Eriksson; Deepti Gurdasani ORCID logo; Arthur Gilly; Lorraine Southam ORCID logo; Emmanouil Tsafantakis; +15 more... Maria Karaleftheri; Janet Seeley ORCID logo; Anatoli Kamali; Gershim Asiki; Iona Y Millwood; Michael Holmes; Huaidong Du; Yu Guo; Meena Kumari; George Dedoussis; Liming Li; Zhengming Chen; Manjinder S Sandhu ORCID logo; Eleftheria Zeggini; Understanding Society Scientific Group; (2019) The transferability of lipid loci across African, Asian and European cohorts. Nature communications, 10 (1). 4330-. ISSN 2041-1723 DOI: 10.1038/s41467-019-12026-7
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Most genome-wide association studies are based on samples of European descent. We assess whether the genetic determinants of blood lipids, a major cardiovascular risk factor, are shared across populations. Genetic correlations for lipids between European-ancestry and Asian cohorts are not significantly different from 1. A genetic risk score based on LDL-cholesterol-associated loci has consistent effects on serum levels in samples from the UK, Uganda and Greece (r = 0.23-0.28, p < 1.9 × 10-14). Overall, there is evidence of reproducibility for ~75% of the major lipid loci from European discovery studies, except triglyceride loci in the Ugandan samples (10% of loci). Individual transferable loci are identified using trans-ethnic colocalization. Ten of fourteen loci not transferable to the Ugandan population have pleiotropic associations with BMI in Europeans; none of the transferable loci do. The non-transferable loci might affect lipids by modifying food intake in environments rich in certain nutrients, which suggests a potential role for gene-environment interactions.


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