Loci with multiple independent single-variant association signals to SNPs with MAF>0.1%.

1<p>FG and TG were LN transformed prior to analysis; the regression coefficient is on the LN scale.</p>2<p>Beta is the estimate of the regression coefficient, and provides the amount and direction the phenotype changes for each copy of the indicated allele.</p>3<p>The p-values come from separate multivariate models for each locus that include all variants listed below, and the first five PCs. P-values shown here represent the independent evidence for the specified variant, after conditioning on the array SNP.</p>4<p>The percent variance in the phenotype accounted for by just the array SNP.</p>5<p>The percent variance in the phenotype accounted for by the array SNP and the independent sequence variants.</p

Rare and common variants contribute to the association signal to HDL-C in gene <i>CETP</i>.

1<p>P-values for rs3764261 and rs5880 may be different from those recorded in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004147#pgen-1004147-t002" target="_blank">Table 2</a> because of the addition of rs2303790 and rs5883 to the model. MAC: minor allele count.</p

Overview of quantitative trait loci investigated in this study.

1<p>The loci are named according to the first gene in the region of interest, starting at the 5′ end of the region.</p>2<p>ROI = region of interest. Number of kb sequenced for the locus.</p>3<p>Total Genes is the number of genes in the locus; Targeted Genes is the number of genes investigated in this study.</p>4<p>Please see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004147#pgen.1004147.s009" target="_blank">Table S3</a> for a complete listing of all variant sites, along with their MAF and annotation.</p>5<p>Phenotype abbreviations: TC = total cholesterol, LDL-C = low density lipoprotein cholesterol, HDL-C = high density lipoprotein cholesterol, TG = triglycerides, FG = Fasting Glucose, FI = Fasting Insulin. Previous association evidence for lipid traits is from Kathiresan <i>et al.</i> 2008, Willer <i>et al.</i> 2008 and Teslovich <i>et al.</i> 2010; for glucose Dupuis <i>et al.</i> 2010, and for insulin Sabatti <i>et al.</i> 2009. The “array SNP” is the GWAS array-genotyped SNP (not sequence variant) with the smallest p-value to indicated traits in this study and is not necessarily the same SNP highlighted in previous studies.</p>6<p>Array SNP MAF and p-values are taken from the current study.</p

Rare and common variants contribute to the association signal to HDL-C in gene <i>ABCA1</i>.

1<p>P-values for rs2575875, rs2066718, and rs2066715 may be different from those recorded in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004147#pgen-1004147-t002" target="_blank">Table 2</a> because of the addition of the three rare variants to the model. MAC: minor allele count.</p

Schematic of rare (MAF<1%) non-synonymous variants used in the gene-level test of total cholesterol (TC) in gene <i>ABCA1</i>.

<p>The x-axis scale (AA) is in amino acid positions. Numbers in parenthesis are the number of copies of the rare variant in persons with phenotype data. The mean TC level in persons possessing variants with bold naming is increased relative to persons without the variant, for all other variants the mean TC level in persons possessing variant alleles is decreased relative to persons without the variant.</p

Schematic of rare (MAF<1%) non-synonymous variants used in the gene-level test HDL-C in gene <i>CETP</i>.

<p>The x-axis scale (AA) is in amino acid positions. Numbers in parenthesis are the number of copies of the rare variant in persons with phenotype data. The mean HDL-C level in persons possessing variants with bold naming is increased relative to persons without the variant, for all other variants the mean HDL-C level in persons possessing variant alleles is decreased relative to persons without the variant.</p

Lipid loci with multiple signals in Europeans.

a<p>LD (<i>r</i>²/D′) with SNP showing the strongest evidence of association at each locus.</p>b<p>β: effect size from an additive model and corresponding to the effect allele, in the unit of mmol/L for HDL-C, LDL-C and natural log transformed TG.</p>c<p><i>P</i> values of sequential conditional analyses, in which we added the SNP with the strongest evidence of association into the regression model as a covariate and tested for the next strongest SNP until the strongest SNP showed a conditional <i>P</i> value>10⁻⁴ and had no annotation suggesting potential function.</p>d<p>Variance explained by SNPs at each locus was estimated based on European samples.</p>e<p><i>P</i> values of initial association in African Americans and East Asians.</p

Trans-ethnic fine-mapping narrowed the association signals.

a<p><i>P</i> meta: <i>P</i> values from meta-analysis combining samples of African American, East Asian and European ancestries.</p>b<p>Direction: effect direction of each individual studies in the order of ARIC, MEC, WHI batch1, WHI batch2, HyperGEN, CLHNS, TAICHI, Finnish T2D, Finnish unaffected, Norwegian T2D and Norwegian unaffected.</p>c<p><i>P</i> het: <i>P</i> values for heterogeneity, indicating whether observed effect sizes are homogeneous across ancestry samples.</p>d<p><i>I</i>²: index of the degree of heterogeneity.</p

Trans-ethnic high-density genotyping narrows the association signal at the HDL-C locus <i>PPP1R3B</i>.

<p>Association in Europeans (A), East Asians (B), African Americans (C) and in a combined trans-ethnic meta-analysis (D). Index SNP rs6601299 colored in purple is the variant showing strongest evidence of association in the combined trans-ethnic meta-analysis.</p

LDL-C locus <i>PCSK9</i> exhibited seven signals in African Americans.

<p>Initial association in the main analysis (A). Residual association in sequential conditional analysis by sequentially adding the lead SNPs into the regression model (B–G). Each SNP was colored according to its LD (<i>r²</i>) in the PAGE consortium, with the strongest SNP colored in purple and symbols designating genomic annotation defined in the ‘annotation key’. Genomic coordinates refer to build 36 (hg18).</p