Participant characteristics for the University of Minnesota (UMN) family-based study population and the Western Australian Raine longitudinal birth cohort.

<p>Participant characteristics for the University of Minnesota (UMN) family-based study population and the Western Australian Raine longitudinal birth cohort.</p

Top SNPs from Raine cohort GWAS that were genotyped in our family population of COME/ROM.

<p>We report our OR and allele frequency using the Risk Allele corresponding to the Risk Allele listed in the Raine cohort GWAS <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104212#pone.0104212-Rye1" target="_blank">[9]</a>.</p><p>*Indicates SNP is intergenic and therefore reports the nearest gene.</p><p>**Indicates SNP is coding.</p>∧<p>Indicates the SNP was a top genotyped SNP from a subset of Raine study participants with full covariate data.</p

Top SNPs from the Raine cohort GWAS that were genotyped in our GWAS of COME/ROM.

<p>We report our OR and allele frequency using the Risk Allele corresponding to the Risk Allele listed in the Raine cohort GWAS <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104212#pone.0104212-Rye1" target="_blank">[9]</a>.</p><p>*Indicates SNP is intergenic and therefore reports the nearest gene.</p>∧<p>Indicates the SNP was a top genotyped SNP from a subset of Raine study participants with full covariate data.</p

Power was computed using TDT Power Calculator [15] varying SNP minor allele frequency (MAF) and genetic relative risk (GRR).

<p>Power was computed using TDT Power Calculator <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104212#pone.0104212-Chen1" target="_blank">[15]</a> varying SNP minor allele frequency (MAF) and genetic relative risk (GRR).</p

Family-based association results between DN-associated SNPs and advanced nephropathy (normoalbuminuria vs. proteinuria/ESRD) among diabetic family members.

#<p>Families  =  number of nuclear families informative for the FBAT analysis.</p><p>S-E(S)  =  observed minus the expected transmission for each allele.</p><p>Var(S)  =  variance of the observed transmission for each allele.</p><p>Z score: positive values indicate risk alleles (i.e., increased transmission to affected individuals), negative values indicate protective alleles (i.e., reduced transmission to affected individuals).</p>*<p>Risk allele reported in <i>Pezzolesi et al</i>. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060301#pone.0060301-Pezzolesi2" target="_blank">[18]</a></p

Summary of genetic additive effects of rs4238001 allele T on HDL-C (log mg/dL), HDL particle number (nmol/L) and HDL particle size (log nm) under a basic model (Model 1).

<p>Analyses were conducted stratified by race/ethnic group and combined by meta-analysis, for all participants as well as stratified by sex (males or female).</p

Schematic of demographic model used in the simulations.

<p>Parameter values were inferred by calibrating to patterns of variation in exome data from 316 European Americans.</p

Spurious association rates in the exome data.

<p>The values are the average spurious association rate for ten run using 1,000 cases and controls from the European Americans in the Exome Sequencing Project. These are the rates at the 5% significance threshold for parameters defined as odds ratios (ORs) of 1/5, 1, or 5 for a fourth, half, or full distance between the minimum and maximum for each axis: PC1 are the columns, and PC2 are the probabilities calculated for each individual. Smaller values indicate larger differences in disease risk among individuals in PC space.</p

Association of the Lipoprotein Receptor <i>SCARB1</i> Common Missense Variant rs4238001 with Incident Coronary Heart Disease

<div><p>Background</p><p>Previous studies in mice and humans have implicated the lipoprotein receptor <i>SCARB1</i> in association with atherosclerosis and lipid levels. In the current study, we sought to examine association of <i>SCARB1</i> missense single nucleotide polymorphism (SNP) rs4238001 with incident coronary heart disease (CHD).</p><p>Methods and Results</p><p>Genotypes for rs4238001 were imputed for 2,319 White, 1,570 African American, and 1,292 Hispanic-American MESA participants using the 1,000 Genomes reference set. Cox proportional hazards models were used to determine association of rs4238001 with incident CHD, with adjustments for age, sex, study site, principal components of ancestry, body mass index, diabetes status, serum creatinine, lipid levels, hypertension status, education and smoking exposure. Meta-analysis across race/ethnic groups within MESA showed statistically significant association of the T allele with higher risk of CHD under a consistent and formally adjudicated definition of CHD events in this contemporary cohort study (hazard ratio [HR]=1.49, 95% CI [1.04, 2.14], <i>P</i> = 0.028). Analyses combining MESA with additional population-based cohorts expanded our samples in Whites (total n = 11,957 with 871 CHD events) and African Americans (total n = 5,962 with 355 CHD events) and confirmed an increased risk of CHD overall (HR of 1.19 with 95% CI [1.04, 1.37], <i>P</i> = 0.013), in African Americans (HR of 1.49 with 95% CI [1.07, 2.06], <i>P</i> = 0.019), in males (HR of 1.29 with 95% CI [1.08, 1.54], <i>P</i> = 4.91x10^-3) and in White males (HR of 1.24 with 95% CI [1.03, 1.51], <i>P</i> = 0.026).</p><p>Conclusion</p><p><i>SCARB1</i> missense rs4238001 is statistically significantly associated with incident CHD across a large population of multiple race/ethnic groups.</p></div

Characteristics of MESA participants across three ethnic groups.

<p>Data are presented as N (%) for binary measures or median [IQR] for continuous measure.</p><p>*Summary statistics are reported for the subset of individuals with data available for at least one of the clinical events.</p><p>†P-values are presented for statistical significance of the difference in values across race/ethnic groups according to a likelihood ratio test with 2 degrees of freedom.</p><p>Characteristics of MESA participants across three ethnic groups.</p