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

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 × 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. 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 × 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. Plasma lipids, including cholesterol and triglyceride (TG), play vital roles in membrane fluidity, hormone and bile synthesis, and energy metabolism. The identification of genetic variants affecting lipoprotein traits, defined as plasma concentrations of TG, HDL, and LDL cholesterol, can give biological insight into both new and old pathways of lipid metabolism. These findings will have potential implications for the diagnosis, prognosis, and treatment of dyslipidemia. In the last two decades, the rare genetic variants responsible for many individually rare dyslipidemia conditions have been discovered, and common variations in many candidate genes have been tested for association with lipoprotein traits. However, in the last year, ten genome-wide association studies (GWAS) have consistently identified association between common genetic variation in multiple novel, as well as previously known, genes and lipoprotein traits in normolipidemic individuals (1Saxena R. Voight B.F. Lyssenko V. Burtt N.P. de Bakker P.I. Chen H. Roix J.J. Kathiresan S. Hirschhorn J.N. Daly M.J. et al.Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.Science. 2007; 316: 1331-1336Crossref PubMed Scopus (2368) Google Scholar, 2Chasman D.I. Pare G. Zee R.Y.L. Parker A.N. Cook N.R. Buring J.E. Kwiatkowski D.J. Rose L.M. Smith J.D. Williams P.T. et al.Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and apolipoprotein B among 6382 white women in genome-wide analysis with replication.Circ. Cardiovasc. Genet. 2008; 1: 21-31Crossref PubMed Scopus (109) Google Scholar, 3Kathiresan S. Melander O. Guiducci C. Surti A. Burtt N.P. Rieder M.J. Cooper G.M. Roos C. Voight B.F. Havulinna A.S. et al.Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.Nat. Genet. 2008; 40: 189-197Crossref PubMed Scopus (1142) Google Scholar, 4Kooner J.S. Chambers J.C. Aguilar-Salinas C.A. Hinds D.A. Hyde C.L. Warnes G.R. Gomez Perez F.J. Frazer K.A. Elliott P. Scott J. et al.Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides.Nat. Genet. 2008; 40: 149-151Crossref PubMed Scopus (267) Google Scholar, 5Sandhu M.S. Waterworth D.M. Debenham S.L. Wheeler E. Papadakis K. Zhao J.H. Song K. Yuan X. Johnson T. Ashford S. et al.LDL-cholesterol concentrations: a genome-wide association study.Lancet. 2008; 371: 483-491Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, 6Wallace C. Newhouse P. K. C. et al.Genome-wide association identifies genes for of cardiovascular and J. Genet. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar, S. A. R. et identified loci lipid concentrations and of Genet. 2008; 40: PubMed Scopus Google Scholar, S. T. et lipid and disease in European Genet. PubMed Scopus Google Scholar, S. G.M. S. K. T. et variants at loci to Genet. PubMed Scopus Google C. A. S. J. T. et al.Genome-wide association analysis of traits in a cohort from a Genet. PubMed Scopus Google The identification of loci with for roles in lipoprotein such as association between the for apolipoprotein and as a for the many new associations between and genes a were (1Saxena R. Voight B.F. Lyssenko V. Burtt N.P. de Bakker P.I. Chen H. Roix J.J. Kathiresan S. Hirschhorn J.N. Daly M.J. et al.Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.Science. 2007; 316: 1331-1336Crossref PubMed Scopus (2368) Google Scholar, 2Chasman D.I. Pare G. Zee R.Y.L. Parker A.N. Cook N.R. Buring J.E. Kwiatkowski D.J. Rose L.M. Smith J.D. Williams P.T. et al.Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and apolipoprotein B among 6382 white women in genome-wide analysis with replication.Circ. Cardiovasc. Genet. 2008; 1: 21-31Crossref PubMed Scopus (109) Google Scholar, 3Kathiresan S. Melander O. Guiducci C. Surti A. Burtt N.P. Rieder M.J. Cooper G.M. Roos C. Voight B.F. Havulinna A.S. et al.Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.Nat. Genet. 2008; 40: 189-197Crossref PubMed Scopus (1142) Google Scholar, 4Kooner J.S. Chambers J.C. Aguilar-Salinas C.A. Hinds D.A. Hyde C.L. Warnes G.R. Gomez Perez F.J. Frazer K.A. Elliott P. Scott J. et al.Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides.Nat. Genet. 2008; 40: 149-151Crossref PubMed Scopus (267) Google Scholar, 5Sandhu M.S. Waterworth D.M. Debenham S.L. Wheeler E. Papadakis K. Zhao J.H. Song K. Yuan X. Johnson T. Ashford S. et al.LDL-cholesterol concentrations: a genome-wide association study.Lancet. 2008; 371: 483-491Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, 6Wallace C. Newhouse P. K. C. et al.Genome-wide association identifies genes for of cardiovascular and J. Genet. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar, S. A. R. et identified loci lipid concentrations and of Genet. 2008; 40: PubMed Scopus Google Scholar, S. T. et lipid and disease in European Genet. PubMed Scopus Google Scholar, S. G.M. S. K. T. et variants at loci to Genet. PubMed Scopus Google C. A. S. J. T. et al.Genome-wide association analysis of traits in a cohort from a Genet. PubMed Scopus Google In loci have been associated at a with at of TG, HDL, or LDL in 13 of genes previously identified to rare for lipid common single nucleotide polymorphism (SNP) variation the same been associated with the same lipoprotein in the of the findings in multiple both to the findings and to the and of the set to replicate the previously identified findings in a population-based the of the or the number of SNPs on a single The two SNP of the or the to multiple individuals on the same The Illumina CVD the using multiple to approximately 50,000 SNPs in individuals on a single S. T. J.C. et and of a cardiovascular SNP for association 2008; PubMed Scopus Google The SNPs were selected for on the CVD based on (1Saxena R. Voight B.F. Lyssenko V. Burtt N.P. de Bakker P.I. Chen H. Roix J.J. Kathiresan S. Hirschhorn J.N. Daly M.J. et al.Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.Science. 2007; 316: 1331-1336Crossref PubMed Scopus (2368) Google to and cardiovascular disease (CVD) D.I. Pare G. Zee R.Y.L. Parker A.N. Cook N.R. Buring J.E. Kwiatkowski D.J. Rose L.M. Smith J.D. Williams P.T. et al.Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and apolipoprotein B among 6382 white women in genome-wide analysis with replication.Circ. Cardiovasc. Genet. 2008; 1: 21-31Crossref PubMed Scopus (109) Google loci in S. Melander O. Guiducci C. Surti A. Burtt N.P. Rieder M.J. Cooper G.M. Roos C. Voight B.F. Havulinna A.S. et al.Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.Nat. Genet. 2008; 40: 189-197Crossref PubMed Scopus (1142) Google genes with a to and J.S. Chambers J.C. Aguilar-Salinas C.A. Hinds D.A. Hyde C.L. Warnes G.R. Gomez Perez F.J. Frazer K.A. Elliott P. Scott J. et al.Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides.Nat. Genet. 2008; 40: 149-151Crossref PubMed Scopus (267) Google a for and SNPs with S. T. J.C. et and of a cardiovascular SNP for association 2008; PubMed Scopus Google The a of SNPs with a of both the and the analysis been as a to for multiple S. K. J. P. de Bakker P.I. Daly M.J. et a set for association and population-based J. Genet. 2007; Full Text Full Text PDF PubMed Scopus Google but for at to the We sought to replicate reported genetic associations with TG, HDL, and LDL using approximately 50,000 SNPs in approximately 2,100 genes in a multiethnic population-based sample using the new Illumina CVD and analysis to and for multiple The by the of and the of for The of and in as a sample in and as previously S. V. S. C. E. H. et in and cardiovascular disease between in the of and in Full Text Full Text PDF PubMed Scopus Google were classified as South Asian (n = their from or Chinese (n = 304) their from or and European (n = their from S. V. S. C. E. H. et in and cardiovascular disease between in the of and in Full Text Full Text PDF PubMed Scopus Google between the of and and have in for or and and blood were from The were using TG, cholesterol apolipoprotein B cholesterol, and HDL cholesterol. LDL cholesterol the in for individuals were on and were from clinical in the multiethnic body mass of and in in in a new body mass of and in in from as previously J. H. S. S. 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Genet. 2007; Full Text Full Text PDF PubMed Scopus Google The reported for a for of with the of the reported using age, sex, and as The or associations reported for the SNPs found on the CVD and the of in the candidate loci the a and to for multiple and the of in the the a and to multiple R. The the a and to multiple R. as by et C. A. S. J. T. et al.Genome-wide association analysis of traits in a cohort from a Genet. PubMed Scopus Google to the However, the the the a and to multiple R. to SNPs found on were in the of × to the the reported traits of SNPs × traits = at a = The two traits and TG were with the traits reported and including in C. A. S. J. T. et al.Genome-wide association analysis of traits in a cohort from a Genet. PubMed Scopus Google and for were on the of the to of on a and the to × = In to a and on all The to a of all for all The for SNP with the of results from all of all the SNPs to as the the and the number of in the of S. K. J. P. de Bakker P.I. 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Williams P.T. et al.Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and apolipoprotein B among 6382 white women in genome-wide analysis with replication.Circ. Cardiovasc. Genet. 2008; 1: 21-31Crossref PubMed Scopus (109) Google Scholar, S. A. R. et identified loci lipid concentrations and of Genet. 2008; 40: PubMed Scopus Google Associations between SNPs the and TG = × the and HDL concentrations = × and the APOE and LDL = × for were identified the SNPs of the previously reported loci were associated using to for multiple association of the and loci with TG, the and HDL and the APOE and LDL (P < 0.05). 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T. et lipid and disease in European Genet. PubMed Scopus Google Scholar, S. G.M. S. K. T. et variants at loci to Genet. PubMed Scopus Google C. A. S. J. T. et al.Genome-wide association analysis of traits in a cohort from a Genet. PubMed Scopus Google and a been reported D.I. Pare G. Zee R.Y.L. Parker A.N. Cook N.R. Buring J.E. Kwiatkowski D.J. Rose L.M. Smith J.D. Williams P.T. et al.Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and apolipoprotein B among 6382 white women in genome-wide analysis with replication.Circ. Cardiovasc. Genet. 2008; 1: 21-31Crossref PubMed Scopus (109) Google and the of the between ethnicities. the cumulative of alleles on plasma lipoprotein concentrations and the proportion of variation can explained by the replicated genetic in a multiethnic a to age, sex, and as as well as the of the number of alleles at the replicated SNPs for of the lipoprotein traits TG, and for HDL, and and for and many of the SNPs in the were associated at the but were previously reported and associated in the sample (P < and identified between the number of alleles and plasma of TG, HDL, and LDL < The age, sex, and the replicated SNPs for of the variation in TG of the variation in HDL and of the variation in LDL concentrations The TG concentration increased from for with or alleles to for with or The HDL concentration from for with 2 or alleles to for with or the LDL concentration increased from for with 2 or alleles to for with or of lipoprotein variation explained by age, sex, and with or replicated genetic as in In a population-based to replicate genetic associations with plasma lipoprotein traits using the curated Illumina CVD SNPs loci LPL, CETP, and were associated with lipoprotein traits, using a or These loci have roles in in plasma lipoprotein concentration from candidate and loci previously associated with at plasma lipoprotein were on the Illumina CVD beadchip, and a SNP associated at (P < 0.05). The SNP or proxy associated in the same direction as previously reported in 13 loci (P < 0.05). The and the of the of loci, the sample We the two (1Saxena R. Voight B.F. Lyssenko V. Burtt N.P. de Bakker P.I. Chen H. Roix J.J. Kathiresan S. Hirschhorn J.N. Daly M.J. et al.Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.Science. 2007; 316: 1331-1336Crossref PubMed Scopus (2368) Google variants in multiple associations with the same in association between to to in or in the and D.I. Pare G. Zee R.Y.L. Parker A.N. Cook N.R. Buring J.E. Kwiatkowski D.J. Rose L.M. Smith J.D. Williams P.T. et al.Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and apolipoprotein B among 6382 white women in genome-wide analysis with replication.Circ. Cardiovasc. Genet. 2008; 1: 21-31Crossref PubMed Scopus (109) Google the reported of biological in or epidemiological a genome-wide We of the associations identified in the studies the of their but underscore the of the associations to and in a clinical cohort of approximately The APOE been associated with plasma lipid concentrations E. A. A. R. de et of apolipoprotein with lipid and 2007; PubMed Scopus Google Scholar, C. T. E. G. polymorphism in the and to lipoprotein Full Text PDF PubMed Google the APOE the associated SNP of which a for from to at which between and on the Illumina CVD and in the same as all SNPs on the of the at and of the a in LDL cholesterol and in TG concentration (P < with previously reported results of associated with LDL cholesterol and TG concentrations with or In a the APOE in the sample and found to associated with plasma lipoprotein concentrations in all the been in many A. S. S. of the polymorphism to plasma lipid traits among South and in Full Text Full Text PDF PubMed Scopus Google been in of the and they on SNP the of using a multiethnic in and variation between to in in the of the association and of the of a a for in a ethnicity. of the in which alleles associated with disease in have been reported P.I. the J. Genet. 2007; Full Text Full Text PDF PubMed Scopus Google to the of to the in genetic or between but they from in between P.I. the J. Genet. 2007; Full Text Full Text PDF PubMed Scopus Google In the the responsible affecting the or the association in the same direction in genetic for Genet. PubMed Scopus Google SNPs associated in the same direction in a multiethnic sample to to the between the tested SNP and the the of the tested SNP to the The of between a SNP and a with genetic for SNPs to the the same associated in the same with the for SNPs a from the In a multiethnic and the of mapping in the a been reported D.I. Pare G. Zee R.Y.L. Parker A.N. Cook N.R. Buring J.E. Kwiatkowski D.J. Rose L.M. Smith J.D. Williams P.T. et al.Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and apolipoprotein B among 6382 white women in genome-wide analysis with replication.Circ. Cardiovasc. Genet. 2008; 1: 21-31Crossref PubMed Scopus (109) Google in the same in the direction of association between in the of direction alleles with the in the previously reported associations over and and S. Melander O. Guiducci C. Surti A. Burtt N.P. Rieder M.J. Cooper G.M. Roos C. Voight B.F. Havulinna A.S. et al.Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.Nat. Genet. 2008; 40: 189-197Crossref PubMed Scopus (1142) Google Scholar, 5Sandhu M.S. Waterworth D.M. Debenham S.L. Wheeler E. Papadakis K. Zhao J.H. Song K. Yuan X. Johnson T. Ashford S. et al.LDL-cholesterol concentrations: a genome-wide association study.Lancet. 2008; 371: 483-491Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, S. G.M. S. K. T. et variants at loci to Genet. PubMed Scopus Google Scholar, C. A. S. J. T. et al.Genome-wide association analysis of traits in a cohort from a Genet. PubMed Scopus Google to a role for in LDL S. Melander O. Guiducci C. Surti A. Burtt N.P. Rieder M.J. Cooper G.M. Roos C. Voight B.F. Havulinna A.S. et al.Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.Nat. Genet. 2008; 40: 189-197Crossref PubMed Scopus (1142) Google been on S. Melander O. Guiducci C. Surti A. Burtt N.P. Rieder M.J. Cooper G.M. Roos C. Voight B.F. Havulinna A.S. et al.Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.Nat. Genet. 2008; 40: 189-197Crossref PubMed Scopus (1142) Google to the of the but the variants responsible for the association with LDL to or the or genes, approximately of responsible for the variation in LDL cholesterol, the associated a to the a to analysis of of the between SNPs the SNP a S. K. J. P. de Bakker P.I. Daly M.J. et a set for association and population-based J. Genet. 2007; Full Text Full Text PDF PubMed Scopus Google been in which SNPs from they However, the and the of In using the the can with the of results for all the of multiple S. K. J. P. de Bakker P.I. Daly M.J. et a set for association and population-based J. Genet. 2007; Full Text Full Text PDF PubMed Scopus Google Scholar, for multiple loci affecting a PubMed Google in which of the on a in which analysis of The of analysis can associations from associations the from a of of and of results will However, in the results of and a were findings the of the of SNPs the from a by the in such a analysis a of disease S. Melander O. Guiducci C. Burtt N.P. Roos C. Hirschhorn J.N. G. et associated with cholesterol and of cardiovascular J. 2008; PubMed Scopus Google type 2 diabetes (1Saxena R. Voight B.F. Lyssenko V. Burtt N.P. de Bakker P.I. Chen H. Roix J.J. Kathiresan S. Hirschhorn J.N. Daly M.J. et al.Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.Science. 2007; 316: 1331-1336Crossref PubMed Scopus (2368) Google and J. H. T. S. S. et of Genet. 2008; PubMed Scopus (109) Google have reported increased for disease with the cumulative number of The number of individuals with as by the and the for disease the J. H. T. S. S. et of Genet. 2008; PubMed Scopus (109) Google in the number of lipoprotein alleles associated with the in plasma LDL and HDL cholesterol concentrations S. Melander O. Guiducci C. Burtt N.P. Roos C. Hirschhorn J.N. G. et associated with cholesterol and of cardiovascular J. 2008; PubMed Scopus Google In a using multiethnic sample and SNPs from replicated loci for the lipoprotein of a lipid were to a between the cumulative number of alleles and plasma lipoprotein with the the of the genetic increased the proportion of variance explained age, sex, and The of the Illumina CVD the sample and number of to the curated of the However, with the of lipid associated loci S. T. et lipid and disease in European Genet. PubMed Scopus Google Scholar, S. G.M. S. K. T. et variants at loci to Genet. PubMed Scopus Google C. A. S. J. T. et al.Genome-wide association analysis of traits in a cohort from a Genet. PubMed Scopus Google the the of the of the The studies to the findings of over and to individuals S. Melander O. Guiducci C. Surti A. Burtt N.P. Rieder M.J. Cooper G.M. Roos C. Voight B.F. Havulinna A.S. et al.Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.Nat. Genet. 2008; 40: 189-197Crossref PubMed Scopus (1142) Google Scholar, 4Kooner J.S. Chambers J.C. Aguilar-Salinas C.A. Hinds D.A. Hyde C.L. Warnes G.R. Gomez Perez F.J. Frazer K.A. Elliott P. Scott J. et al.Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides.Nat. Genet. 2008; 40: 149-151Crossref PubMed Scopus (267) Google Scholar, 5Sandhu M.S. Waterworth D.M. Debenham S.L. Wheeler E. Papadakis K. Zhao J.H. Song K. Yuan X. Johnson T. Ashford S. et al.LDL-cholesterol concentrations: a genome-wide association study.Lancet. 2008; 371: 483-491Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, 6Wallace C. Newhouse P. K. C. et al.Genome-wide association identifies genes for of cardiovascular and J. Genet. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar, S. A. R. et identified loci lipid concentrations and of Genet. 2008; 40: PubMed Scopus Google Scholar, S. T. et lipid and disease in European Genet. PubMed Scopus Google Scholar, S. G.M. S. K. T. et variants at loci to Genet. PubMed Scopus Google C. A. S. J. T. et al.Genome-wide association analysis of traits in a cohort from a Genet. PubMed Scopus Google multiethnic sample of individuals the same as a sample of individuals of the and direction of the between were with the by the SNPs were in all to the variants a common to variants for the between ethnicities. and of results will the analysis of with the results of CVD The in the direction between the potential to associated and in the identification of the responsible In successfully replicated associations between and TG, and TG, and HDL, and APOE and LDL in a multiethnic sample using the new curated Illumina CVD Associations (P < were identified in of the previously identified lipid loci on the CVD beadchip, and the previously reported SNP or proxy associated in 13 of in a a for in but studies will to over of and direction between multiple to associated as in the between the cumulative number of alleles and TG, HDL cholesterol, and LDL cholesterol were The findings indicate the potential utility of the Illumina CVD beadchip, but they underscore the of both sample and and the need to consider meta-analysis of results from commonly studied clinical or epidemiological samples. 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