Sugar-Sweetened Beverage Consumption and Calcified Atherosclerotic Plaques in the Coronary Arteries: The NHLBI Family Heart Study

Background: Sugar-sweetened beverage (SSB) intake is associated with higher risk of weight gain, diabetes, hypertension, cardiovascular disease, and cardiovascular mortality. However, the association of SSB with subclinical atherosclerosis in the general population is unknown. Objective: Our primary objective was to investigate the association between SSB intake and prevalence of atherosclerotic plaque in the coronary arteries in The National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Methods: We studied 1991 participants of the NHLBI Family Heart Study without known coronary heart disease. Intake of SSB was assessed through a semi-quantitative food frequency questionnaire. Coronary artery calcium (CAC) was measured by cardiac Computed Tomography (CT) and prevalent CAC was defined as an Agatston score ≥100. We used generalized estimating equations to calculate adjusted prevalence ratios of CAC. A sensitivity analysis was also performed at different ranges of cut points for CAC. Results: Mean age and body mass index (BMI) were 55.0 years and 29.5 kg/m2, respectively, and 60% were female. In analysis adjusted for age, sex, BMI, smoking, alcohol use, physical activity, energy intake, and field center, higher SSB consumption was not associated with higher prevalence of CAC [prevalence ratio (95% confidence interval) of: 1.0 (reference), 1.36 (0.70–2.63), 1.69 (0.93–3.09), 1.21 (0.69–2.12), 1.05 (0.60–1.84), and 1.58 (0.85–2.94) for SSB consumption of almost never, 1–3/month, 1/week, 2–6/week, 1/day, and ≥2/day, respectively (p for linear trend 0.32)]. In a sensitivity analysis, there was no evidence of association between SSB and prevalent CAC when different CAC cut points of 0, 50, 150, 200, and 300 were used. Conclusions: These data do not provide evidence for an association between SSB consumption and prevalent CAC in adult men and women.

Heritability of 596 lipid species and genetic correlation with cardiovascular traits in the Busselton Family Heart Study

CVD is the leading cause of death worldwide, and genetic investigations into the human lipidome may provide insight into CVD risk. The aim of this study was to estimate the heritability of circulating lipid species and their genetic correlation with CVD traits. Targeted lipidomic profiling was performed on 4,492 participants from the Busselton Family Heart Study to quantify the major fatty acids of 596 lipid species from 33 classes. We estimated narrow-sense heritabilities of lipid species/classes and their genetic correlations with eight CVD traits: BMI, HDL-C, LDL-C, triglycerides, total cholesterol, waist-hip ratio, systolic blood pressure, and diastolic blood pressure. We report heritabilities and genetic correlations of new lipid species/subclasses, including acylcarnitine (AC), ubiquinone, sulfatide, and oxidized cholesteryl esters. Over 99% of lipid species were significantly heritable (h2: 0.06–0.50) and all lipid classes were significantly heritable (h2: 0.14–0.50). The monohexosylceramide and AC classes had the highest median heritabilities (h2 = 0.43). The largest genetic correlation was between clinical triglycerides and total diacylglycerol (rg = 0.88). We observed novel positive genetic correlations between clinical triglycerides and phosphatidylglycerol species (rg: 0.64–0.82), and HDL-C and alkenylphosphatidylcholine species (rg: 0.45–0.74). Overall, 51% of the 4,768 lipid species-CVD trait genetic correlations were statistically significant after correction for multiple comparisons. This is the largest lipidomic study to address the heritability of lipids and their genetic correlation with CVD traits. Future work includes identifying putative causal genetic variants for lipid species and CVD using genome-wide SNP and whole-genome sequencing data.

Abstract P109: Detection of Haplotypes Underlying a Coronary Artery Calcification Linkage Peak in the Family Heart Study

Coronary artery calcification (CAC) is the buildup of calcium deposits in the arteries leading to the heart, and is an indicator of atherosclerosis. CAC is known to have a genetic component, and a genome-wide linkage screen in the Family Heart Study identified significant evidence of linkage on chromosome 9 in the area near rs13293430, but no common variant in the linkage region showed significant evidence of association. Linkage screens attempt to identify covariance due to common ancestry at a genomic locus. This is robust to the presence of rare variation or multiple variants in a region, but is unable to identify the genomic feature causing the signal and additional research is needed to identify potential causative variants. Pairs of individuals who have inherited a locus from a common ancestor will share an identical sequence of alleles (a haplotype) within the region. To identify haplotypes influencing the trait in the region, a mixed effects model was used. CAC was modeled as a trait influenced by polygenic effects and locus-specific haplotype effects. This model has the benefit of jointly estimating the effect of each haplotype while separating the haplotype effect from the background polygenic effect. From the study, 2,687 individuals of European descent from 508 pedigrees with CAC scores were genotyped on the Illumina Human 1M-DuoV3 single nucleotide polymorphisms (SNP) array. Of these, 180 individuals from 23 pedigrees were for subsequent analysis due to membership in a pedigree contributing to the linkage signal. CAC scores were determined by cardiac CT scan and adjusted for age, sex, and principal components before analysis. Phased haplotypes were generated for 906,856 common SNPs across the genome using SHAPEIT. The region between 25Mb and 35Mb (3,500 SNPs) was divided into 250kb sections, and within each section haplotypes were created based on 24 evenly spaced SNPs. Statistical significance for each region was determined by likelihood ratio test. Haplotype analysis identified two regions showing strong evidence of association (p<10 -7 ) with CAC. The region 28-28.25Mb is located completely within the gene LINGO2, which has been associated with BMI and cholesterol. The region 27.5-27.75Mb contains MOBKL2B, IFNK and C9orf72. Additional work will be needed to validate haplotypes used in the model and identify the particular haplotype influencing the trait.