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

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 significan...

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Autores principales: Kuchenbaecker, Karoline, Telkar, Nikita, Reiker, Theresa, Walters, Robin G., Lin, Kuang, Eriksson, Anders, Gurdasani, Deepti, Gilly, Arthur, Southam, Lorraine, Tsafantakis, Emmanouil, Karaleftheri, Maria, Seeley, Janet, Kamali, Anatoli, Asiki, Gershim, Millwood, Iona Y., Holmes, Michael, Du, Huaidong, Guo, Yu, Kumari, Meena, Dedoussis, George, Li, Liming, Chen, Zhengming, Sandhu, Manjinder S., Zeggini, Eleftheria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760173/
https://www.ncbi.nlm.nih.gov/pubmed/31551420
http://dx.doi.org/10.1038/s41467-019-12026-7
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author Kuchenbaecker, Karoline
Telkar, Nikita
Reiker, Theresa
Walters, Robin G.
Lin, Kuang
Eriksson, Anders
Gurdasani, Deepti
Gilly, Arthur
Southam, Lorraine
Tsafantakis, Emmanouil
Karaleftheri, Maria
Seeley, Janet
Kamali, Anatoli
Asiki, Gershim
Millwood, Iona Y.
Holmes, Michael
Du, Huaidong
Guo, Yu
Kumari, Meena
Dedoussis, George
Li, Liming
Chen, Zhengming
Sandhu, Manjinder S.
Zeggini, Eleftheria
author_facet Kuchenbaecker, Karoline
Telkar, Nikita
Reiker, Theresa
Walters, Robin G.
Lin, Kuang
Eriksson, Anders
Gurdasani, Deepti
Gilly, Arthur
Southam, Lorraine
Tsafantakis, Emmanouil
Karaleftheri, Maria
Seeley, Janet
Kamali, Anatoli
Asiki, Gershim
Millwood, Iona Y.
Holmes, Michael
Du, Huaidong
Guo, Yu
Kumari, Meena
Dedoussis, George
Li, Liming
Chen, Zhengming
Sandhu, Manjinder S.
Zeggini, Eleftheria
author_sort Kuchenbaecker, Karoline
collection PubMed
description 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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spelling pubmed-67601732019-09-26 The transferability of lipid loci across African, Asian and European cohorts Kuchenbaecker, Karoline Telkar, Nikita Reiker, Theresa Walters, Robin G. Lin, Kuang Eriksson, Anders Gurdasani, Deepti Gilly, Arthur Southam, Lorraine Tsafantakis, Emmanouil Karaleftheri, Maria Seeley, Janet Kamali, Anatoli Asiki, Gershim Millwood, Iona Y. Holmes, Michael Du, Huaidong Guo, Yu Kumari, Meena Dedoussis, George Li, Liming Chen, Zhengming Sandhu, Manjinder S. Zeggini, Eleftheria Nat Commun Article 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. Nature Publishing Group UK 2019-09-24 /pmc/articles/PMC6760173/ /pubmed/31551420 http://dx.doi.org/10.1038/s41467-019-12026-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kuchenbaecker, Karoline
Telkar, Nikita
Reiker, Theresa
Walters, Robin G.
Lin, Kuang
Eriksson, Anders
Gurdasani, Deepti
Gilly, Arthur
Southam, Lorraine
Tsafantakis, Emmanouil
Karaleftheri, Maria
Seeley, Janet
Kamali, Anatoli
Asiki, Gershim
Millwood, Iona Y.
Holmes, Michael
Du, Huaidong
Guo, Yu
Kumari, Meena
Dedoussis, George
Li, Liming
Chen, Zhengming
Sandhu, Manjinder S.
Zeggini, Eleftheria
The transferability of lipid loci across African, Asian and European cohorts
title The transferability of lipid loci across African, Asian and European cohorts
title_full The transferability of lipid loci across African, Asian and European cohorts
title_fullStr The transferability of lipid loci across African, Asian and European cohorts
title_full_unstemmed The transferability of lipid loci across African, Asian and European cohorts
title_short The transferability of lipid loci across African, Asian and European cohorts
title_sort transferability of lipid loci across african, asian and european cohorts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760173/
https://www.ncbi.nlm.nih.gov/pubmed/31551420
http://dx.doi.org/10.1038/s41467-019-12026-7
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