SNPs significantly (<i>p</i><0.05) associated with at least one lipid trait in at least one ethnic group in our study, as well as those that showed a trend for the same direction of association (<i>p</i> between 0.05–0.20, <i>italic traits</i>) as seen for at least one genome-wide significant lipid trait in the original GWAS^§ (only relevant observations have been included in the table).

§<p>Alternate alleles evaluated as compared to GWAS alleles (in <b>bold</b>), for which opposite effects are expected, are shown in <i>italics</i>. Up-regulated lipid traits are shown in <b>bold</b> vs. down-regulated in unbold. MAF: Minor allele frequency, NHWs: Non-Hispanic Whites, HSPs: Hispanics, ABs: African Blacks, EU: Individuals of European descent included in original GWAS, AA: African American replication sample in original GWAS (* = discordant finding with opposite direction of association), na: not analyzed.</p

SNPs selected from 4 published GWAS in individuals of European ancestry (EU) for replication in our multiethnic sample^§.

§<p>For HDL-C, p-values ranged from 7.7×10⁻⁴ to 0.02 for 4 SNPs (in <i>italics</i>) but were ≤5×10⁻⁸ for other SNPs as well as for other lipid traits included in the table. When available, replication results in African Africans (AA) are also shown (* = discordant finding with opposite direction of association). Primarily implicated genes, associated alleles, and increased lipid levels are shown in <b>bold</b> (decreased levels in unbold). Alleles (on forward or reverse strands) reflect those stated in the original papers.</p

Summary of SNP associations with 4 lipid traits in our multi-ethnic study samples^§.

§<p>Significant p-values (<0.05) are shown in <b>bold</b>. ‘Log10’ transformation was used for HDL-C and TG levels in Non-Hispanic Whites (NHWs) and Hispanics, ‘natural log’ transformation for TC and TG levels in African Blacks, and ‘square root’ transformation for LDL-C and HDL-C levels in African Blacks. The genotypic effects were modeled as the additive effect of the population-specific minor allele in each ethnic group (minor alleles that differed from those in NHWs are shown in <i>italics</i>). The results were adjusted for relevant covariates in each ethnic group. ^*N.A: These SNPs were not analyzed in African Blacks among which they did not have sufficient minor allele frequency (MAF). Six SNPs showed lower genotyping call rate (<95%) in one of the 3 ethnic groups studied (MAF <u>underlined</u>) while the remaining SNPs had high call rates in all ethnic groups. <b>^‡</b>This SNP showed low rate (0.5%) of discrepancy among replicates included in genotyping.</p

Rare/uncommon (MAF<5%) variants analysis with lipid traits in NHWs.

<p>SKAT-O: optimal sequencing Kernel association test, N.RV: number of rare variants, P: p-value.</p><p>Rare/uncommon (MAF<5%) variants analysis with lipid traits in NHWs.</p

Single-site association analysis with lipid traits in African Blacks.

<p>Nucleotide position is according to the reference sequence (Accession # AF261279.1); Chr. Position: chromosomal position is according to NCBI dbSNP human Build 141. ^aBox-Cox transformed variables. MAF: minor allele frequency. HWE-P: Hardy Weinberg equilibrium p-value. RegDB scores: RegulomeDB scores. LDL-C: low-density lipoprotein cholesterol; ApoB: Apolipoprotein B; TG: triglyceride; HDL-C: high-density lipoprotein cholesterol. <b>Bold</b> values represent significant p-values</p><p>Single-site association analysis with lipid traits in African Blacks.</p

Haplotype analysis with lipid traits in African Blacks.

<p>Haplotype windows for LDL-C (<b>a</b>), for ApoB (<b>b</b>), for HDL-C (<b>c</b>), and for TG (<b>d</b>). X-axis has the genotyped markers name and the Y-axis has the –log (global p-value), horizontal lines represent the 4-SNP windows, red-line represents the p-value threshold (p = 0.05) and everything below the threshold is considered non-significant and vice versa.</p

LD Plot of the genotyped variants with MAF>1% in NHWs.

<p>The values in the cells are the pairwise degree of LD indicated by <i>r²</i>×100. <i>r</i>² = 0 is shown as white, 0<<i>r</i>²<1 is shown in gray and <i>r</i>² = 1 is shown in black.</p

Haplotype analysis with lipid traits in NHWs.

<p>Haplotype windows for LDL-C (<b>a</b>), for ApoB (<b>b</b>), for HDL-C (<b>c</b>), and for TG (<b>d</b>). X-axis has the genotyped markers names and the Y-axis has the –log (global p-value), horizontal lines represent the 4-SNP windows, red-line represents the p-value threshold (p = 0.05) and everything below the threshold is considered non-significant and vice versa.</p

Gene-based association analysis with lipid traits in NHWs.

<p>nSNPs: represents the number of SNPs included in the analysis; two rare variants were excluded from the gene-based association analysis because of the missing phenotype data (ApoB data was available in a subset of the NHW sample); Test: represent the overall test statistic; P-value: the overall p-value; SNP p-value: p-value of the best SNPs contributed to the significance.</p><p>Gene-based association analysis with lipid traits in NHWs.</p

Single-site association analysis with lipid traits in NHWs.

<p>* (NA) unavailable results because of missing phenotype data for subjects who carry the rare allele, Nucleotide position is according to the reference sequence (Accession # AF261279.1); Chr. Position: chromosomal position is according to NCBI dbSNP human Build 141. ^aBox-Cox transformed variables. MAF: minor allele frequency. HWE-P: Hardy Weinberg equilibrium p-value.</p><p>RegDB scores: RegulomeDB scores. LDL-C: low-density lipoprotein cholesterol; ApoB: Apolipoprotein B; TG: triglyceride; HDL-C: high-density lipoprotein cholesterol. <b>Bold</b> values represent significant p-values</p><p>Single-site association analysis with lipid traits in NHWs.</p