Low birth weight and longitudinal trends of cardiovascular risk factor variables from childhood to adolescence: the bogalusa heart study

BACKGROUND: Several studies have linked low birth weight to adverse levels of cardiovascular risk factors and related diseases. However, information is sparse at a community level in the U.S. general population regarding the effects of low birth weight on the longitudinal trends in cardiovascular risk factor variables measured concurrently from childhood to adolescence. METHODS: Longitudinal analysis was performed retrospectively on data collected from the Bogalusa Heart Study cohort (n = 1141; 57% white, 43% black) followed from childhood to adolescence by repeated surveys between 1973 and 1996. Subjects were categorized into low birth weight (below the race-specific 10(th )percentile; n = 123) and control (between race-specific 50–75(th )percentile; n = 296) groups. RESULTS: Low birth weight group vs control group had lower mean HDL cholesterol (p = 0.05) and higher LDL cholesterol (p = 0.05) during childhood (ages 4–11 years); higher glucose (p = 0.02) during adolescence. Yearly rates of change from childhood to adolescence in systolic blood pressure (p = 0.02), LDL cholesterol (p = 0.05), and glucose (p = 0.07) were faster, and body mass index (p = 0.03) slower among the low birth weight group. In a multivariate analysis, low birth weight was related independently and adversely to longitudinal trends in systolic blood pressure (p = 0.004), triglycerides (p = 0.03), and glucose (p = 0.07), regardless of race or gender. These adverse associations became amplified with age. CONCLUSIONS: Low birth weight is characterized by adverse developmental trends in metabolic and hemodynamic variables during childhood and adolescence; and thus, it may be an early risk factor in this regard

Principal-component-based multivariate regression for genetic association studies of metabolic syndrome components

<p>Abstract</p> <p>Background</p> <p>Quantitative traits often underlie risk for complex diseases. For example, weight and body mass index (BMI) underlie the human abdominal obesity-metabolic syndrome. Many attempts have been made to identify quantitative trait loci (QTL) over the past decade, including association studies. However, a single QTL is often capable of affecting multiple traits, a quality known as gene pleiotropy. Gene pleiotropy may therefore cause a loss of power in association studies focused only on a single trait, whether based on single or multiple markers.</p> <p>Results</p> <p>We propose using principal-component-based multivariate regression (PCBMR) to test for gene pleiotropy with comprehensive evaluation. This method generates one or more independent canonical variables based on the principal components of original traits and conducts a multivariate regression to test for association with these new variables. Systematic simulation studies have shown that PCBMR has great power. PCBMR-based pleiotropic association studies of abdominal obesity-metabolic syndrome and its possible linkage to chromosomal band 3q27 identified 11 susceptibility genes with significant associations. Whereas some of these genes had been previously reported to be associated with metabolic traits, others had never been identified as metabolism-associated genes.</p> <p>Conclusions</p> <p>PCBMR is a computationally efficient and powerful test for gene pleiotropy. Application of PCBMR to abdominal obesity-metabolic syndrome indicated the existence of gene pleiotropy affecting this syndrome.</p

Utility of waist-to-height ratio in assessing the status of central obesity and related cardiometabolic risk profile among normal weight and overweight/obese children: The Bogalusa Heart Study

<p>Abstract</p> <p>Background</p> <p>Body Mass Index (BMI) is widely used to assess the impact of obesity on cardiometabolic risk in children but it does not always relate to central obesity and varies with growth and maturation. Waist-to-Height Ratio (WHtR) is a relatively constant anthropometric index of abdominal obesity across different age, sex or racial groups. However, information is scant on the utility of WHtR in assessing the status of abdominal obesity and related cardiometabolic risk profile among normal weight and overweight/obese children, categorized according to the accepted BMI threshold values.</p> <p>Methods</p> <p>Cross-sectional cardiometabolic risk factor variables on 3091 black and white children (56% white, 50% male), 4-18 years of age were used. Based on the age-, race- and sex-specific percentiles of BMI, the children were classified as normal weight (5th - 85th percentiles) and overweight/obese (≥ 85th percentile). The risk profiles of each group based on the WHtR (<0.5, no central obesity versus ≥ 0.5, central obesity) were compared.</p> <p>Results</p> <p>9.2% of the children in the normal weight group were centrally obese (WHtR ≥0.5) and 19.8% among the overweight/obese were not (WHtR < 0.5). On multivariate analysis the normal weight centrally obese children were 1.66, 2.01, 1.47 and 2.05 times more likely to have significant adverse levels of LDL cholesterol, HDL cholesterol, triglycerides and insulin, respectively. In addition to having a higher prevalence of parental history of type 2 diabetes mellitus, the normal weight central obesity group showed a significantly higher prevalence of metabolic syndrome (p < 0.0001). In the overweight/obese group, those without central obesity were 0.53 and 0.27 times less likely to have significant adverse levels of HDL cholesterol and HOMA-IR, respectively (p < 0.05), as compared to those with central obesity. These overweight/obese children without central obesity also showed significantly lower prevalence of parental history of hypertension (p = 0.002), type 2 diabetes mellitus (p = 0.03) and metabolic syndrome (p < 0.0001).</p> <p>Conclusion</p> <p>WHtR not only detects central obesity and related adverse cardiometabolic risk among normal weight children, but also identifies those without such conditions among the overweight/obese children, which has implications for pediatric primary care practice.</p

Association of DNA Methylation at \u3cem\u3eCPT1A\u3c/em\u3e Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study

In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10−7 was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6x10-14 and P for cg17058475 = 1.2x10-9). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future

Longitudinal Genome-Wide Association of Cardiovascular Disease Risk Factors in the Bogalusa Heart Study

Peer reviewe

Influence of low birth weight on C-reactive protein in asymptomatic younger adults: the bogalusa heart study

<p>Abstract</p> <p>Background</p> <p>Both low birth weight, an indicator of intrauterine growth restriction, and low grade systemic inflammation depicted by high sensitivity C-reactive protein (hs-CRP) have emerged as independent predictors of cardiovascular (CV) disease and type 2 diabetes. However, information linking low birth weight and hs-CRP in a biracial (black/white) population is scant. We assessed a cohort of 776 black and white subjects (28% black, 43% male) aged 24-43 years (mean 36.1 years) enrolled in the Bogalusa Heart Study with regard to birth weight and gestational age data were retrieved from Louisiana State Public Health Office.</p> <p>Findings</p> <p>Black subjects had significantly lower birth weight than white subjects (3.145 kg vs 3.441 kg, p < 0.0001) and higher hs-CRP level (3.29 mg/L vs 2.57 mg/L, p = 0.011). After adjusting for sex, age, body mass index (BMI), smoking status and race (for total sample), the hs-CRP level decreased across quartiles of increasing birth weight in white subjects (p = 0.001) and the combined sample (p = 0.002). Adjusting for sex, age, BMI, smoking status and race for the total sample in a multivariate regression model, low birth weight was retained as an independent predictor variable for higher hs-CRP levels in white subjects (p = 0.004) and the total sample (p = 0.007). Conversely, the area under the receiver operative curve (c statistic) analysis adjusted for race, sex, age, smoking status and BMI yielded a value of 0.777 with regard to the discriminating value of hs-CRP for predicting low birth weight.</p> <p>Conclusions</p> <p>The deleterious effect of low birth weight on systemic inflammation depicted by the hs-CRP levels in asymptomatic younger adults may potentially link fetal growth retardation, CV disease and diabetes, with important health implications.</p

Genome-wide meta-analysis points to CTC1 and ZNf676 as genes regulating telomere homeostasis in humans

Leukocyte telomere length (LTL) is associated with a number of common age-related diseases and is a heritable trait. Previous genome-wide association studies (GWASs) identified two loci on chromosomes 3q26.2 (TERC) and 10q24.33 (OBFC1) that are associated with the inter-individual LTL variation. We performed a meta-analysis of 9190 individuals from six independent GWAS and validated our findings in 2226 individuals from four additional studies. We confirmed previously reported associations with OBFC1 (rs9419958 P = 9.1 × 10-11) and with the telomerase RNA component TERC (rs1317082, P = 1.1 × 10-8). We also identified two novel genomic regions associated with LTL variation that map near a conserved telomere maintenance complex component 1 (CTC1; rs3027234, P = 3.6 × 10-8) on chromosome17p13.1 and zinc finger protein 676 (ZNF676; rs412658, P = 3.3 × 10-8) on 19p12. The minor allele of rs3027234 was associated with both shorter LTL and lower expression of CTC1. Our findings are consistent with the recent observations that point mutations in CTC1 cause short telomeres in both Arabidopsis and humans affected by a rare Mendelian syndrome. Overall, our results provide novel insights into the genetic architecture of inter-individual LTL variation in the general population.</p

Genome-wide meta-analysis points to CTC1 and ZNf676 as genes regulating telomere homeostasis in humans

Leukocyte telomere length (LTL) is associated with a number of common age-related diseases and is a heritable trait. Previous genome-wide association studies (GWASs) identified two loci on chromosomes 3q26.2 (TERC) and 10q24.33 (OBFC1) that are associated with the inter-individual LTL variation. We performed a meta-analysis of 9190 individuals from six independent GWAS and validated our findings in 2226 individuals from four additional studies. We confirmed previously reported associations with OBFC1 (rs9419958 P = 9.1 × 10-11) and with the telomerase RNA component TERC (rs1317082, P = 1.1 × 10-8). We also identified two novel genomic regions associated with LTL variation that map near a conserved telomere maintenance complex component 1 (CTC1; rs3027234, P = 3.6 × 10-8) on chromosome17p13.1 and zinc finger protein 676 (ZNF676; rs412658, P = 3.3 × 10-8) on 19p12. The minor allele of rs3027234 was associated with both shorter LTL and lower expression of CTC1. Our findings are consistent with the recent observations that point mutations in CTC1 cause short telomeres in both Arabidopsis and humans affected by a rare Mendelian syndrome. Overall, our results provide novel insights into the genetic architecture of inter-individual LTL variation in the general population.</p