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Papers In Press, published online ahead of print July 1, 2009
J. Lipid Res., doi:10.1194/jlr.P900008-JLR200

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Journal of Lipid Research, Vol. 50, 1487-1496, July 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

Replication of genetic associations with plasma lipoprotein traits in a multiethnic sample

Matthew B. Lanktree^*, Sonia S. Anand^,, Salim Yusuf^,, Robert A. Hegele^1,* the SHARE Investigators²

^* Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada
Departments of Medicine and Clinical Epidemiology, McMaster University, Hamilton, Ontario, Canada
² The SHARE Investigators are listed in the Appendix.

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of one table and three figures.

This work was supported by a grant from the Canadian Institute of Health Research, Genome Canada through the Ontario Genomics Institute, and by a Pfizer Jean Davignon Cardiovascular Grant. This work was made possible by the facilities of the Shared Hierarchical Academic Research Computing Network (SHARCNET; www.sharcnet.ca).

Published, JLR Papers in Press, March 18, 2009.

¹ To whom correspondence should be addressed. e-mail: hegele{at}robarts.ca

Recent genome-wide association studies (GWAS) have reproducibly identified loci associated with plasma triglycerides (TG), HDL cholesterol, and LDL cholesterol. We sought to replicate these findings in a multiethnic population-based cohort using the curated single nucleotide polymorphism (SNP) set found on the new Illumina cardiovascular disease (CVD) beadchip, which contains approximately 50,000 SNPs densely mapping approximately 2,100 genes, selected based on their potential role in CVD. The sample consisted of individuals with European (n = 272), South Asian (n = 330), and Chinese (n = 304) ancestry. Identity by state clustering successfully classified individuals according to self-reported ethnicities. Associations between TG and APOA5, TG and LPL, HDL and CETP, and LDL and APOE were all identified (P < 2 x 10^–6). In 13 loci, associations with the same SNP or a proxy SNP were identified in the same direction as previously reported (P < 0.05). Assessing the cumulative number of risk-associated alleles at multiple replicated SNPs increased the proportion of explained lipoprotein variance over and above traditional variables such as age, sex, body mass index, and ethnicity. The findings indicate the potential utility of the Illumina CVD beadchip, but they underscore the need to consider meta-analysis of results from commonly studied clinical or epidemiological samples.

Supplementary key words Beadchip • ethnicity • genomics • false discovery rate • identity by state • linear regression • lipids • permutation analysis • population

Abbreviations: Apo, apolipoprotein; BMI, body mass index; CVD, cardiovascular disease; FDR, false discovery rate; FWER, family-wise error rate; GWAS, genome-wide association study; IBS, identity-by-state; SNP, single nucleotide polymorphism; TC, total cholesterol; TG, triglyceride

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