Childhood body-mass index and the risk of coronary heart disease in adulthood

BACKGROUND: The worldwide epidemic of childhood obesity is progressing at an alarming rate. Risk factors for coronary heart disease (CHD) are already identifiable in overweight children. The severity of the long-term effects of excess childhood weight on CHD, however, remains unknown. METHODS: We investigated the association between body-mass index (BMI) in childhood (7 through 13 years of age) and CHD in adulthood (25 years of age or older), with and without adjustment for birth weight. The subjects were a cohort of 276,835 Danish schoolchildren for whom measurements of height and weight were available. CHD events were ascertained by linkage to national registers. Cox regression analyses were performed. RESULTS: In 5,063,622 person-years of follow-up, 10,235 men and 4318 women for whom childhood BMI data were available received a diagnosis of CHD or died of CHD as adults. The risk of any CHD event, a nonfatal event, and a fatal event among adults was positively associated with BMI at 7 to 13 years of age for boys and 10 to 13 years of age for girls. The associations were linear for each age, and the risk increased across the entire BMI distribution. Furthermore, the risk increased as the age of the child increased. Adjustment for birth weight strengthened the results. CONCLUSIONS: Higher BMI during childhood is associated with an increased risk of CHD in adulthood. The associations are stronger in boys than in girls and increase with the age of the child in both sexes. Our findings suggest that as children are becoming heavier worldwide, greater numbers of them are at risk of having CHD in adulthood

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation

DNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >270,000 independent mQTLs.Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.Molecular Epidemiolog

Childhood overweight following fetal exposure to selective serotonin reuptake inhibitors and maternal psychiatric illness

Abstract 63Luke E Grzeskowiak, Andrew L Gilbert, Thorkild IA Sorensen, Jorn Olsen, Henrik T Sorensen, Lars H Pedersen, Janna L Morriso

Abdominal and gluteofemoral fat depots show opposing associations with postprandial lipemia

Background: High postprandial lipemia is associated with increased risk of cardiovascular disease, independently of fasting lipid concentrations. Abdominal and gluteofemoral fat depots handle lipoproteins differently, which could affect postprandial lipemia and contribute to the relation between abdominal fat distribution and cardiovascular disease risk.Objectives: We aimed to study the influences of higher abdominal compared with gluteofemoral fat on postprandial lipemia after a high-fat meal in individuals with obesity.Methods: A total of 755 adults with obesity from a randomized controlled trial in 7 European countries consumed a liquid high-fat meal. Concentrations of triglycerides (TG), glycerol, free fatty acids, and the cholesterol component of remnant-like particles (RLP), LDL, and HDL were measured postprandially for 3 h. Associations of waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR) with changes in postprandial lipid concentrations. adjusted for fasting concentrations and BMI, were examined using linear regression models. To assess whether the association of WHR with postprandial lipemia could be causal, we performed instrumental variable analyses using a genetic score of 442 variants known to be associated with WHR adjusted for BMI in 2-stage least-squares regression models.Results: WHR was associated with higher TG and RLP cholesterol concentrations, independent of fasting lipid concentrations and BMI. Instrumental variable analyses suggested that the associations of WIIR with postprandial TG (beta = 0.038 mu mol/L*min, SE = 0.019 mu mol/L*min, P = 0.044) and RLP cholesterol concentrations (beta = 0.059 mmol/L, SE = 0.025 mmol/L, P = 0.020) may be causal. WC and HC showed opposite effects: higher WC was associated with higher TG and RLP cholesterol concentrations whereas higher HC was associated with lower concentrations.Conclusions: Our results suggest that higher fat deposition abdominally versus gluteofemorally may be causally associated with elevated postprandial lipemia after a high-fat meal, independent of fasting lipid concentrations and BMI. Furthermore, higher abdominal and gluteofemoral fat depots show opposing effects on postprandial lipemia

Abdominal and gluteofemoral fat depots show opposing associations with postprandial lipemia

Background: High postprandial lipemia is associated with increased risk of cardiovascular disease, independently of fasting lipid concentrations. Abdominal and gluteofemoral fat depots handle lipoproteins differently, which could affect postprandial lipemia and contribute to the relation between abdominal fat distribution and cardiovascular disease risk.Objectives: We aimed to study the influences of higher abdominal compared with gluteofemoral fat on postprandial lipemia after a high-fat meal in individuals with obesity.Methods: A total of 755 adults with obesity from a randomized controlled trial in 7 European countries consumed a liquid high-fat meal. Concentrations of triglycerides (TG), glycerol, free fatty acids, and the cholesterol component of remnant-like particles (RLP), LDL, and HDL were measured postprandially for 3 h. Associations of waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR) with changes in postprandial lipid concentrations. adjusted for fasting concentrations and BMI, were examined using linear regression models. To assess whether the association of WHR with postprandial lipemia could be causal, we performed instrumental variable analyses using a genetic score of 442 variants known to be associated with WHR adjusted for BMI in 2-stage least-squares regression models.Results: WHR was associated with higher TG and RLP cholesterol concentrations, independent of fasting lipid concentrations and BMI. Instrumental variable analyses suggested that the associations of WIIR with postprandial TG (beta = 0.038 mu mol/L*min, SE = 0.019 mu mol/L*min, P = 0.044) and RLP cholesterol concentrations (beta = 0.059 mmol/L, SE = 0.025 mmol/L, P = 0.020) may be causal. WC and HC showed opposite effects: higher WC was associated with higher TG and RLP cholesterol concentrations whereas higher HC was associated with lower concentrations.Conclusions: Our results suggest that higher fat deposition abdominally versus gluteofemorally may be causally associated with elevated postprandial lipemia after a high-fat meal, independent of fasting lipid concentrations and BMI. Furthermore, higher abdominal and gluteofemoral fat depots show opposing effects on postprandial lipemia

Fish consumption does not prevent increase in waist circumference in European women and men

Fish consumption is the major dietary source of EPA and DHA, which according to rodent experiments may reduce body fat mass and prevent obesity. However, human studies have suggested that fish consumption has no appreciable association with body-weight gain. We investigated the associations between fish consumption and subsequent change in waist circumference. Sex, age and waist circumference at enrolment were considered as potential effect modifiers. Women and men (n 89 432) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 5·5 years. Mixed-effect linear regression was used to investigate the associations between fish consumption and subsequent change in waist circumference. Among all participants, the average annual change in waist circumference was - 0·01 cm/10 g higher total fish consumption per d (95 % CI - 0·01, 0·00) and - 0·01 cm/10 g higher fatty fish consumption per d (95 % CI - 0·02, - 0·01), after adjustment for potential confounders. Lean fish consumption was not associated with change in waist circumference. Adjustment for potential over- or underestimation of fish consumption measurements did not systematically change the observed associations, but the 95 % CI became slightly wider. The results in subgroups from analyses stratified by sex, age or waist circumference at enrolment were not systematically different. In conclusion, the present study suggests that fish consumption does not prevent increase in waist circumferenc