Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci ( P = 4.5×10 −8 –1.2×10 −43 ). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing ( p <3×10 −4 ). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D ( p = 4.3×10 −3 , n = 22,044), increased triglycerides ( p = 2.6×10 −14 , n = 93,440), increased waist-to-hip ratio ( p = 1.8×10 −5 , n = 77,167), increased glucose two hours post oral glucose tolerance testing ( p = 4.4×10 −3 , n = 15,234), increased fasting insulin ( p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations ( p = 4.5×10 −13 , n = 96,748) and decreased BMI ( p = 1.4×10 −4 , n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

BackgroundLow dietary intake of the essential nutrient choline and its metabolite betaine may increase atherogenesis both through effects on homocysteine methylation pathways as well as through choline's antioxidants properties. Nutrient values for many common foods for choline and betaine have recently become available in the U.S. nutrient composition database. Our objective was to assess the association of dietary intake of choline and betaine with incident coronary heart disease (CHD), adjusting for dietary intake measurement error.MethodsWe conducted a prospective investigation of the relation between usual intake of choline and betaine with the risk of CHD in 14,430 middle-aged men and women of the biethnic Atherosclerosis Risk in Communities study. A semi-quantitative food frequency questionnaire was used to assess nutrient intake. Proportional hazard regression models were used to calculate the risk of incident CHD. A regression calibration method was used to adjust for measurement error.ResultsDuring an average 14 years of follow-up (1987–2002), 1,072 incident CHD events were documented. Compared with the lowest quartile of intake, incident CHD risk was slightly and non-significantly higher in the highest quartile of choline and choline plus betaine, HR = 1.22 (0.91, 1.64) and HR = 1.14 (0.85, 1.53), controlling for age, sex, education, total energy intake, dietary intakes of folate, methionine and vitamin B6. No association was found between dietary choline intake and incident CHD when correcting for measurement error.ConclusionHigher intakes of choline and betaine were not protective for incident CHD. Similar investigations in other populations are of interest.

Background: We aimed to assess the association of sleep with metabolic syndrome in the 2013/2014 National Health and Nutrition Examination Survey (NHANES). Methods: Sample size included 2737 out of 2013 and 2014 NHANES surveys. Cross-sectional study of metabolic syndrome and sleep duration was conducted. Metabolic syndrome was defined according to NCEP ATPIII (National Cholesterol Education Program Adult Treatment Panel III) criteria. Metabolic syndrome severity score was calculated based on actual measurement of each component, adjusted for sex and race. The generalized additive model (GAM) was built to assess the smooth relationship between metabolic syndrome/metabolic syndrome severity score and sleep duration. Adjustment of models were done for age, sex, race, and sitting time. The value of effective degree of freedom (EDF) formed by the GAM model shows the degree of curvature of the relationship. A value of 1 for EDF is translated as the linear shape of relationship. Values larger than one denote a more complex relationship between the response variable and the predicting one. Results: There was a U-shaped association between sleep duration and metabolic syndrome in univariable GAM (EDF = 2.43, p = 0.06) and multivariable GAM (EDF = 2.03, p = 0.20). The lowest risk of metabolic syndrome was observed in people sleeping 7 hours/night. There was a significant U-shaped association between sleep duration and metabolic syndrome severity score in multivariable GAM (EDF = 2.94, p = 0.0004). Similarly, the lowest mean metabolic syndrome severity score was observed in people sleeping 7 hours/night. There was an effect modification of sex and sleep duration indicating strong U-shaped relationship of metabolic syndrome severity score and sleep duration in women (EDF = 3.43, p = 0.00002) and semi-linear association in men (EDF = 1.76, p = 0.04). Conclusion: Short and long sleep duration was associated with higher risk of metabolic syndrome and higher scores of metabolic syndrome severity score in women. Short sleep duration was associated with higher risk of metabolic syndrome and higher scores of metabolic syndrome severity score in men.

Objective To examine whether fatty liver, and abdominal visceral adipose tissue (VAT) are jointly associated with cardiometabolic abnormalities. Methods and Results African American participants were from the Jackson Heart Study (n=2882, 65% women) who underwent computed tomography. Fatty liver was measured by liver attenuation in Hounsfield Units (LA) and VAT was quantified volumetrically. Cross-sectional associations between LA, VAT, and cardiometabolic risk factors were assessed using linear and logistic regression, and their joint associations were further examined in 4 subgroups - (High-LA/Low-VAT [n=1704], Low-LA/Low-VAT [n=422], High-LA/High-VAT [n=436] and Low-LA/High-VAT [n=320]). Both LA and VAT were associated with most cardiometabolic traits (all p<0.0001), which persisted after additional adjustment for each other (LA, p < 0.01-0.0001 and VAT, p<0.0001). In bootstrap analyses, the regression coefficient of VAT was significantly greater than LA for triglycerides, HDL-C, impaired glucose and metabolic syndrome (MetS) (p range 0.009-0.0001). The interaction between LA and VAT was significant for HDL-C (p=0.002), impaired glucose (p=0.003) and MetS (p=0.04). Among 4 subgroups, participants with higher VAT and lower LA had higher prevalence of cardiometabolic traits than those with each condition alone. Conclusion Both fatty liver and VAT are independent correlates of cardiometabolic risk, but the associations are stronger for VAT than for fatty liver.