Elbers, CC;
Guo, Y;
Tragante, V;
van Iperen, EP;
Lanktree, MB;
Castillo, BA;
Chen, F;
... Keating, BJ; + view all
(2012)
Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.
PLoS One
, 7
(12)
, Article e50198. 10.1371/journal.pone.0050198.
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Abstract
Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p = 8.8×10(-7) and p = 1.5×10(-6) respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 13.5×10(-12)). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report.
| Type: | Article |
|---|---|
| Title: | Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0050198 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0050198 |
| Language: | English |
| Additional information: | © 2012 Elbers et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The CARe Consortium wishes to acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the research institutions, study investigators, field staff and study participants in creating this resource for biomedical research. The following nine parent studies have contributed parent study data, ancillary study data, and DNA samples through the Massachusetts Institute of Technology - Broad Institute (N01-HC-65226) to create this genotype/phenotype database for wide dissemination to the biomedical research community: the Atherosclerosis Risk in Communities (ARIC) study, the Cardiovascular Health Study (CHS), the Cleveland Family Study (CFS), the Cooperative Study of Sickle Cell Disease (CSSCD), the Coronary Artery Risk Development in Young Adults (CARDIA) study, the Framingham Heart Study (FHS), the Jackson Heart Study (JHS), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Sleep Heart Health Study (SHHS). C.C.E is supported by a Rubicon grant from the Netherlands Organization for Scientific Research (NWO). F.W.A. is supported by a clinical fellowship from the Netherlands Organisation for Health Research and Development (ZonMw grant 90700342). Additional funding information can be found in the Supporting Information S1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1380588 |
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