INTRODUCTION: Observational studies have revealed an association between waist circumference (WC) and atrial fibrillation (AF). However, it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk factors. Therefore, the causal role of WC in AF is unclear. This study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization (MR) analysis. METHODS: In our two-sample MR analysis, the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study (GWAS) of WC (42 single nucleotide polymorphisms with a genetic significance of P <5 × 10 -8 ). The data of WC (from the Genetic Investigation of ANthropometric Traits consortium, containing 232,101 participants) and the data of AF (from the European Bioinformatics Institute database, containing 55,114 AF cases and 482,295 controls) were used to assess the causal role of WC on AF. Three different approaches (inverse variance weighted [IVW], MR-Egger, and weighted median regression) were used to ensure that our results more reliable. RESULTS: All three MR analyses provided evidence of a positive causal association between high WC and AF. High WC was suggested to increase the risk of AF based on the IVW method (odds ratio [OR] = 1.43, 95% confidence interval [CI], 1.30-1.58, P = 2.51 × 10 -13 ). The results of MR-Egger and weighted median regression exhibited similar trends (MR-Egger OR = 1.40 [95% CI, 1.08-1.81], P = 1.61 × 10 -2 ; weighted median OR = 1.39 [95% CI, 1.21-1.61], P = 1.62 × 10 -6 ). MR-Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and AF. CONCLUSIONS Our findings suggest that greater WC is associated with an increased risk of AF. Taking measures to reduce WC may help prevent the occurrence of AF.
Humans ; Atrial Fibrillation/genetics* ; Genome-Wide Association Study ; Waist Circumference/genetics* ; Computational Biology ; Databases, Factual

OBJECTIVE: To explore the association between rs2587552 polymorphism (has a strong lin-kage disequilibrium with rs1800497 which had been found in many studies to be related to obesity, r²=0.85) of DRD2 gene and the effect of a childhood obesity intervention in Chinese population, and provide a scientific basis for future personalized childhood obesity intervention based on genetic background. METHODS: From a multi-center cluster randomized controlled trial studying the effect of a childhood obesity intervention, we enrolled 382 children from 8 primary schools (192 and 190 children from intervention and control groups, respectively) in Beijing as study subjects. Saliva was collected and DNA was extracted to detect the rs2587552 polymorphism of DRD2 gene, and the interactions between the gene and study arms on childhood obesity indicators [including body weight, body mass index (BMI), BMI Z-score, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, and body fat percentage] were analyzed. RESULTS: No association was found between rs2587552 polymorphism and the changes in hip circumference or body fat percentage in the intervention group (P>0.05). However, in the control group, children carrying the A allele at DRD2 rs2587552 locus showed a greater increase in hip circumference and body fat percentage compared with those not carrying A allele (P < 0.001). There were interactions between rs2587552 polymorphism of DRD2 gene and study arms on the changes in hip circumference and body fat percentage (P=0.007 and 0.015, respectively). Compared with the control group, children in the intervention group carrying the A allele at DRD2 rs2587552 locus showed decrease in hip circumference by (-1.30 cm, 95%CI: -2.25 to -0.35, P=0.007) and decrease in body fat percentage by (-1.34%, 95%CI: -2.42 to -0.27, P=0.015) compared with those not carrying A allele. The results were consistent between the dominant model and the additive model (hip circumfe-rence: -0.66 cm, 95%CI: -1.28 to -0.03, P=0.041; body fat percentage: -0.69%, 95%CI: -1.40 to 0.02, P=0.056). No interaction was found between rs2587552 polymorphism and study arms on the changes in other childhood obesity-related indicators (P>0.05). CONCLUSION Children carrying the A allele at rs2587552 polymorphism of DRD2 gene are more sensitive to intervention and showed more improvement in hip circumference and body fat percentage after the intervention, suggesting that future personalized childhood obesity lifestyle intervention can be carried out based on the rs2587552 polymorphism of DRD2 gene.
Humans ; Child ; Pediatric Obesity/therapy* ; Prospective Studies ; Polymorphism, Genetic ; Body Mass Index ; Waist Circumference ; Receptors, Dopamine D2/genetics*

Objective: On whole-genome scale, we tried to explore the correlation between obesity-related traits and DNA methylation sites, based on discordant monozygotic twin pairs. Methods: A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district, Yanqing district and Fangshan district in Beijing in 2016. Information on twins was gathered through a self-designed questionnaire and results: from physical examination, including height, weight and waist circumference of the subjects under study. DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip. R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes. Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs). VarFit function of empirical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups. Results According to the obesity discordance criteria, we collected 23 pairs of twins (age range 7 to 16 years), including 12 male pairs. A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis. According to the significance level of FDR set as <0.05, no positive sites would meet this standard. When DMC CpG site cg05684382, with the smallest P value (1.26E-06) as on chromosome 12, the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16. Conclusions: In this study, we analyzed the genome-wide DNA methylation and its correlation with obesity traits. After multiple testing corrections, no positive sites were found to have associated with obesity. However, results from the correlation analysis demonstrated sites cg05684382 (chr: 12) and cg26188191 (chr: 16) might have played a role in the development of obesity. This study provides a methodologic reference for the studies on discordance twins related problems.
Adolescent ; Bayes Theorem ; Beijing ; Body Weight ; Child ; DNA Methylation/genetics* ; Epigenesis, Genetic ; Female ; Genome-Wide Association Study ; Humans ; Male ; Obesity/genetics* ; Twins, Monozygotic ; Waist Circumference

BACKGROUNDCoordinated regulation of nutrient and inflammatory responses by six transmembrane epithelial antigen of prostate 4 (STEAP4) was essential for metabolic homeostasis. STEAP4 expression in human white adipose tissue was associated with obesity. This study aimed to evaluate association between STEAP4 genetic polymorphisms and obesity in Uygur Chinese general population.

METHODSThe functional regions of STEAP4 gene were sequenced in 96 Uygur with obesity (body mass index (BMI) > 30 kg/m²). Representative variations were selected according to the function and linkage disequilibrium and genotyped in 1507 obesity (BMI ≥ 25 kg/m²) and 825 non-obesity control (BMI < 25 kg/m²), all of whom were selected from epidemiology study of obesity-related diseases during January to February 2007 among Uygur population in Hetian area of Xinjiang Uygur Autonomous Region.

RESULTSFourteen novel and 6 known single nucleotide polymorphism (SNPs), including 2 nonsynonymous SNPs (nsSNPs), in the STEAP4 gene were identified. Of the 3 representative SNPs, the nsSNP rs1981529 (Gly75Asp, 224A/G) was significantly associated with obesity phenotype (additive P/Pc = 0.001/0.006, dominant P/Pc = 0.003/0.018, odds ratio (OR) and 95% confidence interval (CI) adjusted for age, gender and drinking 0.755 (0.641 - 0.890) and 0.750 (0.621 - 0.907), respectively). By the multiple linear regression analysis, the quantitative phenotypes of BMI (P/Pc = 0.002/0.004) and waist circumference (P/Pc = 0.004/0.008) were found to be significantly associated with the genotypes of rs1981529 (Gly75Asp, 224A/G) in Uygur general population, and effect size (beta value) of one allele G of rs1981529 (Gly75Asp, 224A/G) was - 0.553 kg/m² for BMI and - 1.311 cm for waist circumference after controlling age, gender and drinking factors.

CONCLUSIONSThe present study shows an association of the common variation rs1981529 (Gly75Asp, 224A/G) in the STEAP4 gene with obesity in Uygur general population. Further studies should replicate the results using larger populations.

Adult ; Asian Continental Ancestry Group ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Linkage Disequilibrium ; genetics ; Male ; Membrane Proteins ; genetics ; Middle Aged ; Obesity ; genetics ; Oxidoreductases ; genetics ; Polymorphism, Single Nucleotide ; genetics ; Waist Circumference ; genetics

OBJECTIVETo determine the prevalence and clinical phenotype of metabolic syndrome among overweight and obese schoolchildren in Beijing, and to compare the rates of diagnosis made according to the criteria of the National Cholesterol Education Program (NCEP) of the United States and International Diabetes Federation (IDF).

METHODSBased on Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study with body mass index (BMI), waist circumference (WC) and blood pressure measured, the overweight and obese children were screened among nearly 20 000 children 6-18 years of age in Beijing by Chinese BMI cutoffs for schoolchildren (7-18 years) and the US 2000 CDC Growth Charts--the 85th and 95th percentile (6 years) and were enrolled as the study population. Simultaneously a group of children with normal BMI were selected as the control group and based on the international method of age grouping, each of the above groups was divided further into 4 sub-groups in terms of age: 6-9, 10-12, 13-15 and 16-18 years old, respectively. Fasting plasma glucose (FPG) and insulin (FINS), serum high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) were examined. HOMA-IR index was calculated for estimating individual insulin resistance. A child who met any three or more of the following five criteria, according to NCEP definition, was diagnosed as MS. A diagnosis of MS using IDF definition required abdominal obesity plus any two or more of the other four criteria: (1) abnormal obesity: WC > or = P(90); (2) elevated BPs: SBP/DBP > or = P(90); (3) low HDL-C: HDL-C < 1.03 mmol/L (40 mg/dl); (4) high TG: TG > or = 1.24 mmol/L (110 mg/dl); (5) impaired fasting glucose (IFG): FPG > or = 5.6 mmol/L (100 mg/dl).

RESULTSThe prevalence rates of MS by NCEP definition were: 0.9%, 7.6% and 29.8% in the normal weight (control group), overweight and obese children, respectively, which were higher than the rates diagnosed by IDF definition with 0.1%, 5.2% and 28.6% in the three groups. The prevalence rates of individual MS component among obese children were: 81.6% for abnormal obesity, 47.7% for elevated BPs, 35.6% for high TG, 16.9% for low HDL-C, and 13.4% for IFG. Elevated BPs (29.8%), abnormal obesity (27.4%) and high TG (26.0%) were the leading three abnormalities among overweight children. With the increase of BMI, the clustering of MS components and insulin resistance (HOMA-IR) were remarkably increased. HOMA-IR significantly increased as the number of MS component increased.

CONCLUSIONSMS has been in an epidemic status among the obese schoolchildren in Beijing. Abnormal obesity, elevated BPs and high TG were the three most common metabolic abnormalities for overweight and obese children. The prevalence rates of MS by NCEP definition in the present study was higher than those diagnosed by using IDF definition.

Adolescent ; Blood Glucose ; analysis ; Body Mass Index ; Body Weight ; Child ; China ; epidemiology ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Diabetes Mellitus, Type 2 ; metabolism ; Growth Charts ; Humans ; Insulin ; analysis ; Insulin Resistance ; genetics ; physiology ; Male ; Metabolic Syndrome ; physiopathology ; Obesity ; epidemiology ; metabolism ; physiopathology ; Obesity, Abdominal ; pathology ; Overweight ; epidemiology ; etiology ; metabolism ; Prevalence ; Triglycerides ; analysis ; Waist Circumference