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Objectives: Central obesity poses significant health risks because it increases susceptibility to multiple chronic diseases. Epigenetic features such as DNA methylation may be associated with specific obesity traits, which could help us understand how genetic and environmental factors interact to influence the development of obesity. This study aims to identify DNA methylation sites associated with the waist circumference (WC) in Northern Han Chinese population, and to elucidate potential causal relationships., Methods: A total of 59 pairs of WC discordant monozygotic twins (ΔWC >0) were selected from the Qingdao Twin Registry in China. Generalized estimated equation model was employed to estimate the methylation levels of CpG sites on WC. Causal relationships between methylation and WC were assessed through the examination of family confounding factors using FAmiliaL CONfounding (ICE FALCON). Additionally, the findings of the epigenome-wide analysis were corroborated in the validation stage., Results: We identified 26 CpG sites with differential methylation reached false discovery rate (FDR) < 0.05 and 22 differentially methylated regions (slk-corrected p < 0.05) strongly linked to WC. These findings provided annotations for 26 genes, with notable emphasis on MMP17, ITGA11, COL23A1, TFPI, A2ML1-AS1, MRGPRE, C2orf82, and NINJ2. ICE FALCON analysis indicated the DNA methylation of ITGA11 and TFPI had a causal effect on WC and vice versa (p < 0.05). Subsequent validation analysis successfully replicated 10 (p < 0.05) out of the 26 identified sites., Conclusions: Our research has ascertained an association between specific epigenetic variations and WC in the Northern Han Chinese population. These DNA methylation features can offer fresh insights into the epigenetic regulation of obesity and WC as well as hints to plausible biological mechanisms., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

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., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Introduction: The purpose of this study was to determine the possible differences in genetic polymorphisms and serum levels of chromogranin A (CgA), according to age and sex, in subjects with and without metabolic syndrome (MetS)., Methodology: The genotyping and serum level of CgA and biochemical parameters were measured by the T-ARMS-PCR and PCR-RFLP and ELISA and spectrophotometer methods, respectively., Results: A comparison of males with and without MetS showed significantly lower high-density lipoprotein-cholesterol (HDL-C) levels than those of females.At ages 30-70 years, both sexes showed significant differences in triglycerides (TG), fasting blood sugar (FBS), CgA levels and waist circumference (WC) when compared to the two groups. Both sexes with MetS indicated significant differences in systolic blood pressure (SBP) at ages 40-70 years, while at ages 40-59 years, there was a significant difference in HDL-C level in males.There was a significant correlation between serum levels of FBS, TG, SBP and WC (in both sexes), and CgA in subjects with MetS. Significant correlation was found between HDL-C level and diastolic blood pressure (DBP), and CgA level in males and females, respectively. CgA genotype frequency (T-415C and C+87T polymorphisms) showed no significant differences between males and females with and without MetS, while there was only a significant difference in frequency of the genotypes T-415C when compared to males with and without MetS., Conclusion: The CgA appears to be strongly associated with MetS components in both sexes. Variation in CgA gene expression may affect the T-415C polymorphism in males. This may mean that the structure of CgA genetics differs in different ethnic groups. Differences in the serum level and expression of CgA gene may show valuable study results that it may be expected a relationship between these variables and the MetS., Competing Interests: The authors declared no conflict of interest., (© 2024 Journal of the ASEAN Federation of Endocrine Societies.)

Although many individuals are able to achieve weight loss, maintaining this loss over time is challenging. We aimed to study whether genetic predisposition to general or abdominal obesity predicts weight regain after weight loss. We examined the associations between genetic risk scores for higher BMI and higher waist-to-hip ratio adjusted for BMI (WHRadjBMI) with changes in weight and waist circumference up to 3 years after a 1-year weight loss program in participants (n = 822 women, n = 593 men) from the Look AHEAD (Action for Health in Diabetes) study who had lost ≥3% of their initial weight. Genetic predisposition to higher BMI or WHRadjBMI was not associated with weight regain after weight loss. However, the WHRadjBMI genetic score did predict an increase in waist circumference independent of weight change. To conclude, a genetic predisposition to higher WHRadjBMI predicts an increase in abdominal obesity after weight loss, whereas genetic predisposition to higher BMI is not predictive of weight regain. These results suggest that genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain., Article Highlights: Nearly all individuals who intentionally lose weight experience weight regain. Individuals with a higher genetic risk for abdominal adiposity experience increased regain in waist circumference after weight loss. Genetic predisposition to higher BMI does not predict weight regain after weight loss., (© 2023 by the American Diabetes Association.)

Background: The Fat-mass and obesity-associated-gene (FTO gene) and sedentary behavior time are associated with obesity. However, whether sedentary behavior time can modify the genetic predisposition to obesity in the Chilean population is unknown. Therefore, this study investigated the association between sedentary behavior, adiposity markers, and the FTO gene., Methods: This cross-sectional study included 409 participants from the Genes, Environment, Diabetes, and Obesity (GENADIO) study. Adiposity markers studied included body weight, body mass index (BMI), waist circumference (WC), and fat mass. Sedentary behaviors were measured using accelerometers. Using multiple regression, we evaluated the interaction between sedentary behaviors and the FTO gene (rs9939609) on adiposity markers., Results: Sedentary behaviors and the FTO genotype were positively associated with higher body weight, BMI, WC, and fat mass. However, the association between time of sedentary behavior and adiposity markers was higher in carriers of the risk variant for the FTO gene. For each hour of increment in sedentary behaviors, body weight increases by 1.36 kg ([95% CI: 0.27; 2.46], p = 0.015) and 2.95 kg ([95%CI: 1.24; 4.65], p = 0.001) in non-risk carriers (TT) versus risk carriers (AA), respectively. We observed similar results for WC, BMI, and body fat, but the interaction was significant only for WC., Conclusion: The association between sedentary behaviors and adiposity markers, especially body weight and WC, is higher in individuals who carry the risk variant of the FTO gene.

While non-alcoholic fatty liver disease (NAFLD) has been widely studied, the pathophysiology of lean NAFLD, the critical NAFLD subgroup, remains elusive. This study aimed to clarify the association between polymorphisms of GCKR, waist circumference, and the odds of lean NAFLD in the elderly Chinese Han population who live in the Zhangjiang community center of Shanghai, China. Three single nucleotide polymorphisms (SNPs), including rs1260326, rs780093, and rs780094, were genotyped in MassARRAY Analyzer. The association between SNPs with waist circumference in five genetic models was analyzed and rechecked by the logistic regression analysis. Mediation models were established to evaluate whether the waist circumstance can mediate the association between SNPs and lean NAFLD. In this study, the frequency of the C allele of rs1260326, rs780093, and rs780094 was significantly lower in lean NAFLD individuals than in lean non-NAFLD ones. The association between rs1260326 in GCKR and the odds of lean NAFLD was mediated via waist circumference after adjusting gender and age in the elderly Chinese Han population (β = 1.196, R 2  = 0.043, p = 0.020). For the first time, this study examined the mediating effect of waist circumference on the association between rs1260326 in GCKR and the odds of lean NAFLD (β = 0.0515, 95% CI 0.0107-0.0900, p = 0.004). It may contribute to illustrating the pathogenesis of lean NAFLD and indicate that waist circumference management might improve lean NAFLD control., (© 2023. The Author(s).)

Background:  Obesity, especially abdominal obesity, is an independent indicator of increased cardiovascular risk. Observational studies have shown an observational association between obesity and venous thromboembolism (VTE). As a type of VTE, pulmonary embolism (PE) is also associated with obesity. However, it is unclear whether the observed associations are causal or caused by confounding bias or reverse causality., Methods:  We performed a two-sample test by obtaining the exposure dataset of waist circumference (WC) and hip circumference (HC) from the Neale Laboratory Consortium's genome-wide association study summary data and the summary-level outcome data of VTE and PE from FinnGen Biobank of European ancestry to determine the causal effect of WC and HC on VTE and PE., Results:  All three Mendelian randomization methods displayed a positive association between WC/HC and VTE/PE. WC and HC were positively associated with VTE (odds ratio [OR] = 1.803 per 1 standard deviation [SD] increase in WC, 95% confidence interval [CI] = 1.393-2.333; p  < 0.001; OR = 1.479 per 1 SD increase in HC, 95% CI = 1.219-1.796; p  < 0.001, respectively). Furthermore, we found a causal association between genetically predicted WC/HC and a higher risk of PE (OR = 1.929 per 1 SD increase in WC, 95% CI = 1.339-2.778, p  < 0.001; OR = 1.431 per 1 SD increase in HC, 95% CI =1.095-1.869; p  = 0.009, respectively)., Conclusion:  There is a significant causal relationship between WC/HC and VTE/PE, which is consistent with observational studies. Taking measures to reduce WC/HC of obesity may help reduce the incidence of VTE/PE., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: The behavior of anthropometrics and the relationship with genetic factors through a long-term perspective should be better explored. This study aims to verify the odds of maintaining the nutritional status classification after three years, according to the rs9939609 polymorphism (FTO gene)., Methods: It was a retrospective longitudinal study with 355 schoolchildren (7-17 years). Body mass index, body-fat percentage (BF%), and waist circumference (WC) were measured at baseline and follow-up. The FTO gene was evaluated from blood collection and genotyping performed by real-time polymerase chain reaction. Odds ratios and 95% confidence intervals were calculated., Results: For those homozygous with the A allele, the odds of being at less favorable classification at follow-up were 2.29 (1.24; 4.22) and 4.05 (2.08; 7.86) times higher than expected for BF% and WC, respectively, whereas the odds of being in the more favorable classification at follow-up were 0.34 (0.12; 0.93) and 0.11 (0.01; 0.78) for BF% and WC, respectively. The odds of being at less favorable classification were higher for AA carriers with less favorable classification at baseline for BF% and WC compared to AT and TT carriers., Conclusions: Schoolchildren with a genetic predisposition to obesity and unfavorable anthropometric profile at baseline had more chances of maintaining their nutritional status after three years of follow-up., (© 2023. The Author(s).)

Objective: The present study tested the interactive effects of childhood adversity and polygenic risk scores for waist circumference (PRS-WC) on waist circumference (WC). Consistent with a diathesis-stress model, we hypothesize that the relationship between PRS-WC and WC will be magnified by increasing levels of childhood adversity., Methods: Observational study of 7976 adults (6347 European Americans and 1629 African Americans) in the Health and Retirement Study with genotyped data. PRS-WC were calculated by the HRS administrative core using the weighted sum of risk alleles based on a genome-wide association study conducted by the Genetic Investigation of Anthropometric Traits (GIANT) consortium. Childhood adversity was operationalized using a sum score of three traumatic events that occurred before the age of 18 years., Results: There was a statistically significant interaction between PRS-WC and childhood adversity for European Americans, whereby the magnitude of PRS-WC predicting WC increased as the number of adverse events increased., Conclusions: This study supports the idea of the interactive effects of genetic risks and childhood adversity on obesity. More epidemiological studies, particularly with understudied populations, are needed to better understand the roles that genetics and childhood adversity play on the development and progression of obesity., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Using body mass index (BMI) as a proxy, previous Mendelian randomization (MR) studies found total causal effects of general obesity on polycystic ovarian syndrome (PCOS). Hitherto, total and direct causal effects of general- and central obesity on PCOS have not been comprehensively analyzed., Objectives: To investigate the causality of central- and general obesity on PCOS using surrogate anthropometric markers., Methods: Summary GWAS data of female-only, large-sample cohorts of European ancestry were retrieved for anthropometric markers of central obesity (waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR)) and general obesity (BMI and its constituent variables-weight and height), from the IEU Open GWAS Project. As the outcome, we acquired summary data from a large-sample GWAS (118870 samples; 642 cases and 118228 controls) within the FinnGen cohort. Total causal effects were assessed via univariable two-sample Mendelian randomization (2SMR). Genetic architectures underlying causal associations were explored. Direct causal effects were analyzed by multivariable MR modelling., Results: Instrumental variables demonstrated no weak instrument bias (F > 10). Four anthropometric exposures, namely, weight (2.69-77.05), BMI (OR: 2.90-4.06), WC (OR: 6.22-20.27), and HC (OR: 6.22-20.27) demonstrated total causal effects as per univariable 2SMR models. We uncovered shared and non-shared genetic architectures underlying causal associations. Direct causal effects of WC and HC on PCOS were revealed by two multivariable MR models containing exclusively the anthropometric markers of central obesity. Other multivariable MR models containing anthropometric markers of both central- and general obesity showed no direct causal effects on PCOS., Conclusions: Both and general- and central obesity yield total causal effects on PCOS. Findings also indicated potential direct causal effects of normal weight-central obesity and more complex causal mechanisms when both central- and general obesity are present. Results underscore the importance of addressing both central- and general obesity for optimizing PCOS care., Competing Interests: The authors have declared that no competing interests exist.

We analyzed the contribution of genetic factors on the association between puberty timing and body mass index (BMI) using longitudinal data and two approaches: (i) genetic twin design and (ii) polygenic scores (PGS) of obesity indices. Our data were derived from Finnish cohorts: 9080 twins had information on puberty timing and BMI and 2468 twins also had genetic data. Early puberty timing was moderately associated with higher BMI in childhood in both boys and girls; in adulthood these correlations were weaker and largely disappeared after adjusting for childhood BMI. The largest proportion of these correlations was attributable to genetic factors. The higher PGSs of BMI and waist circumference were associated with earlier timing of puberty in girls, whereas weaker associations were found in boys. Early puberty is not an independent risk factor for adult obesity but rather reflects the association between puberty timing and childhood BMI contributed by genetic predisposition., (© 2022. The Author(s).)

Leukocyte telomere length (LTL) is associated with obesity and may be involved in its aetiology, but few studies have focused on children and most have been cross-sectional. We assessed the relation of LTL with adiposity development in a prospective study of Colombian children. We quantified LTL at enrollment in 722 children aged 5-12 years and measured anthropometry annually for a median 6 years. Using mixed effects models, we estimated changes in adiposity measures including BMI and waist circumference (WC)-for-age z-scores in relation to baseline LTL z-score. In girls, longer LTL was linearly related to a lower increase in WC z-score from age 6 to 16 years. Every 1 SD LTL was associated with an adjusted 0.13 units lower increase in WC (95% CI: -0.23, -0.03; p = 0.01). In conclusion, longer LTL among girls in middle childhood is associated with smaller increases in WC, an indicator of abdominal adiposity., (© 2021 World Obesity Federation.)

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with waist circumference (WC) and waist-to-hip ratio (WHR) adjusted for BMI (WCadjBMI and WHRadjBMI), but it remains unclear whether these SNPs relate to change in WCadjBMI or WHRadjBMI with lifestyle intervention for weight loss. We hypothesized that polygenic scores (PS) comprised of 59 SNPs previously associated with central adiposity would predict less of a reduction in WCadjBMI or WHRadjBMI at 8-10 weeks in two lifestyle intervention trials, NUGENOB and DiOGenes, and at 1 year in five lifestyle intervention trials, Look AHEAD, Diabetes Prevention Program, Diabetes Prevention Study, DIETFITS, and PREDIMED-Plus. One-SD higher PS related to a smaller 1-year change in WCadjBMI in the lifestyle intervention arms at year 1 and thus predicted poorer response (β = 0.007; SE = 0.003; P = 0.03) among White participants overall and in White men (β = 0.01; SE = 0.004; P = 0.01). At average weight loss, this amounted to 0.20-0.28 cm per SD. No significant findings emerged in White women or African American men for the 8-10-week outcomes or for WHRadjBMI. Findings were heterogeneous in African American women. These results indicate that polygenic risk estimated from these 59 SNPs relates to change in WCadjBMI with lifestyle intervention, but the effects are small and not of sufficient magnitude to be clinically significant., (© 2022 by the American Diabetes Association.)

Background: Genetic factors along with inadequate lifestyle habits are associated with the development of cardiometabolic alterations. Thus, the present study aimed to examine the role of sedentary behavior on the relationship between rs9939609 polymorphism (fat mass and obesity-associated gene-FTO) and cardiometabolic risk score according to cardiorespiratory fitness (CRF) levels in children and adolescents., Methods: A cross-sectional study with 1215 children and adolescents (692 girls), aged between 6 and 17 years. Screen time as a marker of sedentary behavior was evaluated through a self-reported questionnaire and CRF was estimated using the 6-min walking and running test. The genotyping of the FTO rs9939609 polymorphism was performed using a real-time polymerase chain reaction. Clustered cardiometabolic risk score (cMetS) was calculated by summing z-scores of total cholesterol/high-density lipoprotein cholesterol ratio, triglycerides, glucose, systolic blood pressure, and waist circumference, and dividing it by five. Moderation analyses were tested using multiple linear regression models., Results: The coefficient of the interaction term of FTO (rs9939609) and screen time indicated that screen time was a significant moderator on the relationship between FTO rs9939609 polymorphism and cMetS (p = 0.047) in children and adolescents classified with low CRF (β = 0.001; 95% CI = 0.001; 0.002). It was observed a significant association between genotype risk (AA) of FTO polymorphism and cMetS, in participants that spent more than 378 min a day in front of screen-based devices (β = 0.203; 95% CI = 0.000; 0.405). No interaction term was found for those with high CRF., Conclusions: High sedentary behavior seems to influence the relationship between genetic predisposition to obesity and cardiometabolic risk factors in children and adolescents with low CRF., (© 2022. The Author(s).)

This population-based longitudinal study is the first investigation that assesses the association of common MC4R SNPs with the obesity-related parameters over time and determines the effect of risk alleles during the three adulthood life periods (early, middle, and late) in a large Iranian cohort, a population with a unique genetic make-up that has been understudied and relatively unexplored. We obtained the genotype of 5370 unrelated adults who participated in the ongoing Tehran Cardiometabolic Genetic Study (TCGS) cohort project for the common MC4R SNPs. Linear regression and linear mixed model analyses were performed to examine the effect of MC4R polymorphisms on maximum BMI and other obesity-related factors over time. We recognized that several SNPs associated with the maximum BMI and the increased BMI, waist circumference, and waist-hip ratio across Iranian adults over a lifetime. Interestingly, we found that rs9954571-A has a yet unreported protective role against obesity-related factors, including BMI, waist circumference, waist-hip ratio, and triglyceride level. Additionally, a survey of the impact of the MC4R risk score throughout the adulthood life periods indicated that the MC4R risk score is influenced both the elevated BMI and waist circumference only during the early adulthood period. Our findings can expand our knowledge about the MC4R genetic variant's contributions to adulthood obesity and highlight the importance of evaluating the genetic components affecting obesity over a lifetime, which could be considered for obesity clinical screening and treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Backgrounds: To investigate associations of genetic and environmental factors with coronary artery disease (CAD), we collected medical reports, lifestyle details, and blood samples of 2113 individuals, and then used the polymerase chain reaction (PCR)-ligase detection reaction (LDR) to genotype the targeted 102 SNPs., Methods: We adopted elastic net algorithm to build an association model that considered simultaneously genetic and lifestyle/clinical factors associated with CAD in Chinese Han population., Results: In this study, we developed an all covariates-based model to explain the risk of CAD, which incorporated 8 lifestyle/clinical factors and a gene-score variable calculated from 3 significant SNPs (rs671, rs6751537 and rs11641677), attaining an area under the curve (AUC) value of 0.71. It was found that, in terms of genetic variants, the AA genotype of rs671 in the additive (adjusted odds ratio (OR) = 2.51, p = 0.008) and recessive (adjusted OR = 2.12, p = 0.021) models, the GG genotype of rs6751537 in the additive (adjusted OR = 3.36, p = 0.001) and recessive (adjusted OR = 3.47, p = 0.001) models were associated with increased risk of CAD, while GG genotype of rs11641677 in additive model (adjusted OR = 0.39, p = 0.044) was associated with decreased risk of CAD. In terms of lifestyle/clinical factors, the history of hypertension (unadjusted OR = 2.37, p < 0.001) and dyslipidemia (unadjusted OR = 1.82, p = 0.007), age (unadjusted OR = 1.07, p < 0.001) and waist circumference (unadjusted OR = 1.02, p = 0.05) would significantly increase the risk of CAD, while height (unadjusted OR = 0.97, p = 0.006) and regular intake of chicken (unadjusted OR = 0.78, p = 0.008) reduced the risk of CAD. A significantinteraction was foundbetween rs671 and dyslipidemia (the relative excess risk due to interaction (RERI) = 3.36, p = 0.05)., Conclusion: In this study, we constructed an association model and identified a set of SNPs and lifestyle/clinical risk factors of CAD in Chinese Han population. By considering both genetic and non-genetic risk factors, the built model may provide implications for CAD pathogenesis and clues for screening tool development in Chinese Han population., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The prevalence of obesity and its related chronic diseases have been increasing especially in Asian countries. Obesity-related genetic variants have been identified, but these explain little of the variation in BMI. Recent studies reported associations between DNA methylation and obesity, mostly in non-Asian populations., Methods: We performed an epigenome-wide association study (EWAS) on general adiposity (body mass index, BMI) and abdominal adiposity (waist circumference, WC) in 409 multi-ethnic Asian individuals and replicated BMI and waist-associated DNA methylation CpGs identified in other populations. The cross-lagged panel model and Mendelian randomization were used to assess the temporal relationship between methylation and BMI. The temporal relationship between the identified CpGs and inflammation and metabolic markers was also examined., Results: EWAS identified 116 DNA methylation CpGs independently associated with BMI and eight independently associated with WC at false discovery rate P FDR  < 0.05 in 409 Asian samples. We replicated 110 BMI-associated CpGs previously reported in Europeans and identified six novel BMI-associated CpGs and two novel WC-associated CpGs. We observed high consistency in association direction of effect compared to studies in other populations. Causal relationship analyses indicated that BMI was more likely to be the cause of DNA methylation alteration, rather than the consequence. The causal analyses using BMI-associated methylation risk score also suggested that higher levels of the inflammation marker IL-6 were likely the consequence of methylation change., Conclusion: Our study provides evidence of an association between obesity and DNA methylation in multi-ethnic Asians and suggests that obesity can drive methylation change. The results also suggested possible causal influence that obesity-related methylation changes might have on inflammation and lipoprotein levels., (© 2021. The Author(s).)

Background and Aims: Central obesity is a condition that poses a significant risk to global health and requires the employment of novel scientific methods for exploration. The objective of this study is to use DNA methylation analysis to detect DNA methylation loci linked to obesity phenotypes, i.e. waist circumference and waist-to-hip ratio adjusted for BMI., Methods and Results: Two-hundred and ten healthy European participants from the STANISLAS Family Study (SFS), comprising 73 nuclear families, were comprehensively assessed for methylation status using Illumina Infinium HumanMethylation450 BeadChip. An epigenome-wide association study was performed, which identified a CpG site cg16170243 located on chromosome 18q21.2 significantly associated with waist circumference, after adjusting for BMI (β = 2.32, SE = 0.41, P adj  = 0.048). Cg16170243 corresponds to a 50 bp-length human methylation oligoprobe located within the AC090241.2 gene that overlaps ST8SIA5 gene. No significant association was observed with waist-to-hip ratio adjusted for BMI (P adj  > 0.05)., Conclusions: A novel association between DNA methylation and WC was identified, which is demonstrating that epigenetic mechanisms may have a significant impact on waist circumference ratio in healthy individuals. Further studies are warranted to address the causal effects of this association., (© 2021. The Author(s).)

Context: Atrial fibrillation (AF), cardiac arrhythmias, and related risk factors are common in patients with Cushing's syndrome, or clinical chronic hypercortisolism. While hypercortisolism may be associated with AF, this association has not yet been ascertained causally., Objective: To determine whether plasma cortisol is causally associated with AF using a 2-sample Mendelian randomization (MR) design., Methods: Three genetic variants in the SERPINA1/SERPINA6 locus and functionally associated with plasma cortisol were identified in the CORtisol NETwork consortium (12 597 participants). Summary-level genome-wide association study (GWAS) data for the associations between the cortisol-associated variants and AF were obtained from a GWAS meta-analysis of 6 studies (60 620 AF cases and 970 216 noncases) and the FinnGen consortium (17 325 AF cases and 97 214 noncases). The fixed-effects inverse-variance weighted approach accounting for genetic correlations between variants was used for analysis. Multivariable MR analyses were conducted to assess potential mediating effects of systolic blood pressure (SBP) and waist circumference (WC). Summary-level GWAS data for SBP and WC were obtained respectively from the International Consortium of Blood Pressure (757 601 participants) and the Genetic Investigation of ANthropometric Traits consortium (232 101 participants)., Results: One standard deviation increase in genetically predicted plasma cortisol was associated with greater risk of AF (odds ratio [OR] 1.20, 95% CI 1.06-1.35). The association attenuated when adjusting for genetically predicted SBP and WC (OR 0.99, 95% CI 0.72-1.38)., Conclusion: Evidence derived from the MR study suggests a positive association between plasma cortisol and risk of AF, likely mediated through SBP and WC., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: The question whether the proportion of energy provided by fat and carbohydrates in the diet is associated with body mass index (BMI) and waist circumference (WC) is an important public health issue, but determining causality is difficult in epidemiological studies., Objectives: Using a two-sample bidirectional Mendelian randomization (MR) in both a univariable and multivariable setting, we aimed to determine whether the relative proportion of different macronutrients in the diet (in % of total energy intake (E%)) is causally related to BMI and WC and vice versa., Methods: All analyses were based on genome-wide association studies including 268,922 Europeans with dietary data (SSGAC Consortium) and at least 232,101 with anthropometric measures (GIANT Consortium). An inverse-variance weighted approach using modified second-order weights within the radial regression framework was performed. Radial MR-Egger, weighted median and mode, Robust Adjusted Profile Score (RAPS), and Pleiotropy RESidual Sum and Outlier (PRESSO) methods were used in sensitivity analyses to verify MR assumptions. Additionally, multivariable MR was conducted to account for inter correlation between macronutrient intakes. All estimates represent the standard deviation (SD) change in each outcome per one SD change in the respective exposure., Results: We found that genetically predicted relative carbohydrate intake (E%) reduced BMI (β = -0.529; 95% CI: -0.745, -0.312; P-value = 2⋅10 -6 ) and WC (β = -0.459; 95% CI: -0.656, -0.262; P-value = 5⋅10 -6 ). Both effects were also supported by the multivariable approach: β = -0.441 (95% CI: -0.772, -0.109; P-value = 0.009) for BMI and β = -0.410 (95% CI: -0.667, -0.154; P-value = 0.002) for WC. Genetically predicted dietary intake of fat (E%) was weaker and positively related to both anthropometric measures. We obtained evidence that a higher BMI and WC increased the relative dietary intake of fat and protein (E%). For example, each SD higher BMI increased protein intake (E%) by 0.114 SD (95% CI: 0.081, 0.147; P-value = 9⋅10 -12 ) and each SD higher WC increased protein intake (E%) by 0.078 SD (95% CI: 0.035, 0.121; P-value = 4⋅10 -4 ). Sensitivity analyses confirmed these findings revealing consistent effect estimates., Conclusions: Using genetic information to improve causal inference we found evidence, that a low relative carbohydrate proportion (E%) and a high proportion of fat (E%) in the diet is causally related to a higher BMI and a higher WC. Further research considering carbohydrate, fat, and protein quality and possible consequences on micronutrient intake is needed to define the implications for dietary intake recommendations., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims/introduction: Recent studies have suggested C-X-C motif chemokine ligand 14 (CXCL14), secreted from adipose tissue, to play an important role in the pathogenesis of metabolic syndrome. However, the clinical significance of CXCL14 in humans has not been elucidated. This study aimed to assess correlations between serum CXCL14 levels and clinical parameters in patients with type 2 diabetes mellitus., Materials and Methods: In total, 176 individuals with type 2 diabetes mellitus were recruited. Serum CXCL14 concentrations were determined by enzyme-linked immunosorbent assay. We examined the associations of serum CXCL14 levels with laboratory values, abdominal computed tomography image information, surrogate markers used for evaluating the pathological states of diabetes, obesity and atherosclerosis., Results: Serum CXCL14 levels correlated positively with body mass index, waist circumference, subcutaneous and visceral fat areas, and serum alanine transaminase, uric acid, total cholesterol, low-density lipoprotein cholesterol, triglycerides and C-peptide (CPR) levels. In contrast, CXCL14 levels correlated inversely with age, pulse wave velocity and serum adiponectin levels. Multiple linear regression analysis showed serum levels of CPR (β = 0.227, P = 0.038) and the fatty liver index (β = 0.205, P = 0.049) to be the only parameters showing independent statistically significant associations with serum CXCL14 levels., Conclusions: Serum CXCL14 levels were independently associated with serum CPR and fatty liver index in patients with type 2 diabetes mellitus. In these patients, a high serum CPR concentration might reflect insulin resistance rather than β-cell function, because CXCL14 showed simple correlations with obesity-related parameters. Collectively, these data suggested that serum CXCL14 levels in type 2 diabetes patients might be useful predictors of elevated serum CPR and hepatic steatosis., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background and Aims: Natural variation in body fat is explained by both genetic and environmental effects. Epigenetic mechanisms such as DNA methylation can mediate these effects causing changes in gene expression leading to onset of obesity. Studies of genetic isolates have the potential to provide new epigenetic insights with advantages such as reduced genetic diversity and environmental exposures., Methods and Results: This was an exploratory study of genome-wide DNA methylation in relation to body fat traits in 47 healthy adults from the genetic isolate of Norfolk Island. Quantitative body fat traits (body fat percentage, body mass index, hip circumference, waist circumference, waist-hip-ratio and weight) were carefully measured. DNA methylation data was obtained from peripheral blood using Illumina 450K arrays. Multi-trait analysis was performed using Principal Component Analysis (PCA). CpG by trait association testing was performed using stepwise linear regressions. Two components were identified that explained approximately 89% of the phenotypic variance. In total, 5 differential methylated positions (DMPs) were identified at genome-wide significance (P≤ 2.4 × 10 -7 ), which mapped to GOT2-CDH8, LYSMD3, HIBADH, ADGRD1 and EBF4 genes. Gene set enrichment analysis of 848 genes containing suggestive DMPs (P≤ 1.0 × 10 -4 ) implicated the Cadherin (28 genes, P adj  = 6.76 × 10 -7 ) and Wnt signaling pathways (38 genes, P adj  = 7.78 × 10 -6 )., Conclusion: This study provides new insights into the epigenetically influenced genes and pathways underlying body fat variation in a healthy cohort and provides targets for consideration in future studies of obesity risk., Competing Interests: Declaration of competing interest All authors declared to have no conflict of interest., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Obesity is the most crucial phenotype in metabolic syndrome (MetS), and waist circumference (WC) and body mass index (BMI) are two common indexes to define obesity. It is an accepted fact that genetic and environmental interaction influence obesity and MetS. Microsatellites are a subcategory of tandem repeats with a length of 1 to 10 nucleotides. Tandem repeats make up repetitive genomic regions. Differences in the number of tandem repeats or their variation (alleles) result in microsatellite polymorphisms. Thus, we attempted to find microsatellite variation associated with WC and BMI in a family-based study. Twelve microsatellite markers were selected to investigate possible genes or chromosomal regions in 91 families with at least one affected MetS. The cut-off values for BMI and WC were considered 25 kg/m 2 and 90 cm, respectively. In all members of the families, the strongest association was observed between the marker D11S1304 (allele 1) with both WC and BMI, independently, by the biallelic model in the family-based association test analysis (P < 0.05). Besides, when we compared high- and low-level groups in members with MetS, the markers D8S1743 and D11S1304 (allele 1) showed a strong association with WC (P = 0.0080) and BMI (P = 0.0074), respectively. When the simultaneous detection of the high WC and MetS status was used as a trait, the strongest association was observed with the marker D8S1743 (P = 0.0034). Moreover, when BMI with the high MetS status was used as a trait, the strongest association was observed with the marker D8S1743 (allele 4) (P = 0.0034). The obtained results showed a relationship between obesity and MetS with markers on the selected regions on chromosomes 8 and 11, and to a lesser degree, on chromosome 12.

The prevalence of obesity has been increasing sharply and has become a serious public health problem worldwide. Gene-environment interaction in obesity is a relatively new field, and little is known about it in Chinese adults. This study aimed to provide the effects of gene-environment interaction on obesity among Chinese adults. A stratified multistage cluster sampling method was conducted to recruit participants from 150 surveillance sites. Subjects born in 1960, 1961 and 1963 were selected. An exploratory factor analysis was used to classify the environmental factors. The interaction of single nucleotide polymorphisms (SNPs) and environmental factors on body mass index (BMI) and waist circumference were analyzed using a general linear model. A multiple logistic regression model combined with an additive model was performed to analyze the interaction between SNPs and environmental factors in obesity and central obesity. A total of 2216 subjects were included in the study (mean age, 49.7 years; male, 39.7%, female, 60.3%). Engaging in physical activity (PA) could reduce the effect of MC4R rs12970134 on BMI (β = -0.16kg/m 2 , p = 0.030), and also reduce the effect of TRHR rs7832552 and BCL2 rs12454712 on waist circumference (WC). Sedentary behaviors increased the effects of SNPs on BMI and WC, and simultaneously increased the effects of FTO rs9939609 and FTO rs8050136 on obesity and central obesity. A higher socioeconomic status aggravated the influence of SNPs (including FTO rs9939609, BNDF rs11030104, etc.) on BMI and WC, and aggravated the influence of SEC16B rs574367 on central obesity. The MC4R rs12970134 association with BMI and the FTO rs8050136 association with central obesity appeared to be more pronounced with higher energy intake (β = 0.140 kg/m 2 , p = 0.049; OR = 1.77, p = 0.004, respectively). Engaging in PA could reduce the effects of SNPs on BMI and WC; nevertheless, a higher socioeconomic status, higher dietary energy intake and sedentary behaviors accentuated the influences of SNPs on BMI, WC, obesity and central obesity. Preventative measures for obesity should consider addressing the gene-environment interaction.

Background: Lipid metabolism disorders, especially hypertriglyceridemia (HTG), are risk factors for non-alcoholic fatty liver disease (NAFLD). However, the association between genetic factors related to HTG and the risk of NAFLD has been scarcely studied., Methods: A total of 185 subjects with moderate HTG were prospectively included. We investigated the association between genetic factors' (five allelic variants with polygenic hypertriglyceridemia) clinical and biochemical biomarkers with NAFLD severity. The five allelic variants' related clinical and biochemical data of HTG were studied in all the subjects. NAFLD was assessed by abdominal ultrasound and patients were divided into two groups, one with no or mild NAFLD and another with moderate/severe NAFLD., Results: Patients with moderate/severe NAFLD had higher weight and waist values and a higher prevalence of insulin resistance than patients with no or mild NAFLD. Moderate/severe NAFLD was independently associated with APOA5 rs3134406 and ZPR1 rs964184 variants, and also showed a significant inverse relationship with lipoprotein(a) [Lp(a)] concentrations., Conclusions: APOA5 rs3135506 and ZPR1 rs964184 variants and lipoprotein(a) are associated with moderate/severe NAFLD. This association was independent of body weight, insulin resistance, and other factors related to NAFLD.

Objective: We aimed to examine the associations of obesity-related traits (body mass index [BMI], central obesity) and their genetic predisposition with the risk of developing severe COVID-19 in a population-based data., Research Design and Methods: We analyzed data from 489,769 adults enrolled in the UK Biobank-a population-based cohort study. The exposures of interest are BMI categories and central obesity (e.g., larger waist circumference). Using genome-wide genotyping data, we also computed polygenic risk scores (PRSs) that represent an individual's overall genetic risk for each obesity trait. The outcome was severe COVID-19, defined by hospitalization for laboratory-confirmed COVID-19., Results: Of 489,769 individuals, 33% were normal weight (BMI, 18.5-24.9 kg/m 2 ), 43% overweight (25.0-29.9 kg/m 2 ), and 24% obese (≥30.0 kg/m 2 ). The UK Biobank identified 641 patients with severe COVID-19. Compared to adults with normal weight, those with a higher BMI had a dose-response increases in the risk of severe COVID-19, with the following adjusted ORs: for 25.0-29.9 kg/m 2 , 1.40 (95%CI 1.14-1.73; P = 0.002); for 30.0-34.9 kg/m 2 , 1.73 (95%CI 1.36-2.20; P < 0.001); for 35.0-39.9 kg/m 2 , 2.82 (95%CI 2.08-3.83; P < 0.001); and for ≥40.0 kg/m 2 , 3.30 (95%CI 2.17-5.03; P < 0.001). Likewise, central obesity was associated with significantly higher risk of severe COVID-19 (P < 0.001). Furthermore, larger PRS for BMI was associated with higher risk of outcome (adjusted OR per BMI PRS Z-score 1.14, 95%CI 1.05-1.24; P = 0.004)., Conclusions: In this large population-based cohort, individuals with more-severe obesity, central obesity, or genetic predisposition for obesity are at higher risk of developing severe-COVID-19., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Both inflammation and oxidative stress may contribute to pathogenesis of metabolic syndrome (MetS). The C242T polymorphism (rs4673) in the CYBA gene, as the main components of NAD (P) H oxidase, causes inter-individual variability in the enzyme activity. We aimed to investigate the association between this polymorphism with MetS and its components., Methods: Two hundred nine patients with MetS and 232 controls were included in this study. MetS was defined based on NCEP ATP-III A criteria with some modifications. The C242T polymorphism within CYBA gene was determined by using PCR-based restriction fragment length polymorphism (PCR-RFLP) method., Results: After applying a multiple logistic regression model with adjusting for potential confounders of MetS including, age, sex, body mass index, hypertension, used medications, and diabetes mellitus, C242T polymorphism was found to be associated with the presence of MetS in men but not in the total population or in women. T allele as compared to C allele was associated with decreased odds of MetS in men (adjusted OR = 0.42, 95% CI = 0.24-0.74; P = .003), but not in women (adjusted OR = 1.03, 95% CI = 0.07-1.61; P = .890), or in the total population (adjusted OR = 0.72, 95% CI = 0.51-1.02; P = .063)., Conclusion: This study shows that T allele of C242T polymorphism in CYBA gene is protective against MetS in Iranian men but not in women. Further cohort studies with larger sample size in subgroups of men and women are required to confirm such association in other racial or ethnic group., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation.)

Objective : The present study examined whether physical activity, personality, cognition, education, and depressive symptoms mediate the association between polygenic scores (PGS) for body mass index (BMI) and waist circumference and the corresponding phenotypic adiposity measures. Design : Participants were 9,139 individuals aged 50 to 107 years (57% women; Mean Age: 68.17, SD: 10.06) from the Health and Retirement Study who were genotyped. Trained staff measured their height, weight, and waist circumference, and participants answered questions on physical activity, personality, education, cognitive function, and depressive symptoms. Main Outcome Measures: BMI and waist circumference. Results: A higher PGS for both BMI and waist circumference were related to higher phenotypic BMI and waist circumference, respectively, in part through their association with lower physical activity, conscientiousness, education, and higher depressive symptoms but not cognition. The mediators accounted for 6.6% of the association between PGS and BMI and 9.6% of the association between PGS and waist circumference. Conclusion: The present study provides new evidence on the multiple, distinct pathways through which genetic propensity to higher BMI and waist circumference may lead to higher adiposity in adulthood. Individuals with a higher genetic predisposition to obesity may gain more weight through less adaptive behavioral, personality and educational profiles.

Salivary amylase, encoded by the AMY1 gene, is responsible for the digestion of carbohydrates. We investigated associations of AMY1 genetic variations with general and central adiposity changes considering dietary carbohydrate intake among 32,054 adults from four prospective cohort studies. A genetic risk score (GRS) was calculated based on nine AMY1 single-nucleotide polymorphisms, with higher AMY1-GRS indicating higher activity of salivary amylase. We meta-analyzed interactions between AMY1-GRS and dietary intake for changes in general and central adiposity over 5.5-10 years. We found that carbohydrate food intake significantly altered associations of AMY1-GRS with changes in BMI ( P interaction = 0.001) and waist circumference ( P interaction < 0.001). Results were consistent and significant in female cohorts rather than in male cohorts. Among women, higher AMY1-GRS was associated with more increases in adiposity if dietary carbohydrate food intake was high, while higher AMY1-GRS was associated with less gains in adiposity when the dietary intake was low. Also, in a 2-year randomized dietary intervention trial, associations of AMY1-GRS with changes in weight ( P interaction = 0.023) and waist circumference ( P interaction = 0.037) were significantly modified by carbohydrate intake. Our results suggest the importance of precision nutrition strategies considering participants' genetic adaptation to carbohydrate-rich diets in regulating general and central adiposity., (© 2020 by the American Diabetes Association.)

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disorder which accounts for high morbidity and mortality due to complications like renal failure, amputations, cardiovascular disease, and cerebrovascular events., Methods: We collected medical reports, lifestyle details, and blood samples of individuals and used the polymerase chain reaction-ligase detection reaction method to genotype the SNPs, and a visit was conducted in August 2016 to obtain the incidence of Type 2 diabetes in the 2113 eligible people. To explore which genes and environmental factors are associated with type 2 diabetes mellitus in a Chinese Han population, we used elastic net to build a model, which is to explain which variables are strongly associated with T2DM, rather than predict the occurrence of T2DM., Result: The genotype of the additive of rs964184, together with the history of hypertension, regular intake of meat and waist circumference, increased the risk of T2DM (adjusted OR = 2.38, p = 0.042; adjusted OR = 3.31, p < 0.001; adjusted OR = 1.05, p < 0.001). The TT genotype of the additive and recessive models of rs12654264, the CC genotype of the additive and dominant models of rs2065412, the TT genotype of the additive and dominant models of rs4149336, together with the degree of education, regular exercise, reduced the risk of T2DM (adjusted OR = 0.46, p = 0.017; adjusted OR = 0.53, p = 0.021; adjusted OR = 0.59, p = 0.021; adjusted OR = 0.57, p = 0.01; adjusted OR = 0.59, p = 0.021; adjusted OR = 0.57, p = 0.01; adjusted OR = 0.50, p = 0.007; adjusted OR = 0.80, p = 0.032) ., Conclusion: Eventually we identified a set of SNPs and environmental factors: rs5805 in the SLC12A3, rs12654264 in the HMGCR, rs2065412 and rs414936 in the ABCA1, rs96418 in the ZPR1 gene, waistline, degree of education, exercise frequency, hypertension, and the intake of meat. Although there was no interaction between these variables, people with two risk factors had a higher risk of T2DM than those only having one factor. These results provide the theoretical basis for gene and other risk factors screening to prevent T2DM.

Background: Fat mass and obesity-associated gene (FTO) is the most studied obesity-related gene up to date. We aimed to assess anthropometric indices in carriers of FTO rs9939609 polymorphism with overweight across Iranian population (Shiraz) to find out the associations of this polymorphism with obesity indices., Methods: This was a cross-sectional study conducted on 198 overweight healthy adults aged 20-45 years old. We assessed the body composition of the participants using bioelectrical impedance analyzer. In addition, we measured the waist circumference (WC) and hip circumference (HC). Waist to hip ratio (WHR) and waist to height ratio (WHtR) were also calculated by equations. The participants' genotype was determined by ARMS-PCR. Also, data analysis was performed using SPSS software version 20 and R software version 3.6.2., Results: The mean values of body mass index (BMI) and age of the participants were 26.93 ± 1.13 kg/m 2 and 33.33 ± 6.35 years old, respectively. Homozygous carriers of A-allele had significantly higher values for BMI (0.60 kg/m 2 , p = 0.026), WHR (0.04 unit, p = 0.003), and WHtR (0.02 unit, p = 0.030) than the homozygous carriers of T-allele. Individuals with AA genotype had greater WC (2.66 cm, p = 0.042, and 4.03 cm, p = 0.002), fat mass (2.24 kg, p = 0.004, and 3.02 kg, p = 0.001), and trunk fat (1.53 kg, p = 0.001, and 2.08 kg, p = 0.001) compared to those with AT and TT genotypes, respectively. Interestingly, after adjustment of the confounders, significant associations were observed among rs9939609 polymorphism and BMI, Wt, WC, trunk fat percentage, WHR, and WHtR., Conclusions: A-allele of the FTO rs9939609 polymorphism was indicated to be associated with greater general and central obesity in adult population of Shiraz, Iran.

Previous studies have shown that men and women have different genetic architectures across many traits. However, except waist-to-hip ratio (WHR) and waist circumference (WC), it remains unknown whether the genetic effects of a certain trait are weaker or stronger on men/women. With ~18 000 Taiwan Biobank subjects, we comprehensively investigate sexual heterogeneity in autosomal genetic effects, for traits regarding cardiovascular health, diabetes, kidney, liver, anthropometric profiles, blood, etc. 'Gene-by-sex interactions' (G $\times$ S) were detected in 18 out of 26 traits, each with an interaction P-value (${{P}}&#95;{{INT}}$) less than $0.05/104={0.00048}$, where 104 is the number of tests conducted in this study. The most significant evidence of G $\times$ S was found in WHR (${{P}}&#95;{{INT}}$ = 3.2 $\times{{10}}^{-{55}}$) and WC (${{P}}&#95;{{INT}}$ = 2.3$\times{{10}}^{-{41}}$). As a novel G$\times$S investigation for other traits, we here find that the autosomal genetic effects are weaker on women than on men, for low-density lipoprotein cholesterol (LDL-C), uric acid (UA) and diabetes-related traits such as fasting glucose and glycated hemoglobin. For LDL-C and UA, the evidence of G$\times$S is especially notable in subjects aged less than 50 years, where estrogen can play a role in attenuating the autosomal genetic effects of these two traits. Men and women have systematically distinct environmental contexts caused by hormonal milieu and their specific society roles, which may trigger diverse gene expressions despite the same DNA materials. As many environmental exposures are difficult to collect and quantify, sex can serve as a good surrogate for these factors., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Investigations on the impact of genetic factors on the development of obesity have been limited regarding the Roma population-the largest and most vulnerable ethnic minority in Europe of Asian origin. Genetic variants identified from genetic association studies are primarily from European populations. With that in mind, we investigated the applicability of data on selected obesity-related single nucleotide polymorphisms (SNPs), obtained from the Hungarian general (HG) population of European origin, on the Hungarian Roma (HR) population. Twenty preselected SNPs in susceptible alleles, known to be significantly associated with obesity-related phenotypes, were used to estimate the effect of these SNPs on body mass index (BMI) and waist circumference (WC) in HG ( N = 1783) and HR ( N = 1225) populations. Single SNP associations were tested using linear and logistic regression models, adjusted for known covariates. Out of 20 SNPs, four located in FTO (rs1121980, rs1558902, rs9939609, and rs9941349) showed strong association with BMI and WC as continuous variables in both samples. Computations based on Adult Treatment Panel III (ATPIII) and the International Diabetes Federation's (IDF) European and Asian criteria showed rs9941349 in FTO to be associated only with WC among both populations, and two SNPs (rs2867125, rs6548238) in TMEM18 associated with WC only in HG population. A substantial difference (both in direction and effect size) was observed only in the case of rs1801282 in PPARγ on WC as a continuous outcome. Findings suggest that genetic risk scores based on counting SNPs with relatively high effect sizes, defined based on populations with European ancestry, can sufficiently allow estimation of genetic susceptibility for Roma. Further studies are needed to clarify the role of SNP(s) with protective effect(s).

Objective: This study aims to determine whether genetic variants in ACE I/D and AGT M235T are associated with overweight-obesity and body mass index (BMI) in a Tunisian population., Methods: We designed an age- and sex-matched case-control study. The height and weight were measured and BMI was calculated. A total of 259 overweight-obese patients and 369 healthy controls were genotyped for the ACE I/D and AGT M235T genes using polymerase chain reaction and restriction fragment length polymorphism., Results: ACE I/D and AGT M235T genes were associated with BMI, waist circumference and overweight-obesity (p⩽0.001). In an additive model, the I and the M alleles in ACE and AGT variants, respectively, were associated with a lower BMI: -1.45 and -2.29 units, respectively. ACE I/D genotypes were associated with dyslipidemia; AGT M235T genotypes with dyslipidemia and total cholesterol., Conclusion: These data suggest that variations in ACE I/D and AGT M235T affect the risk of overweight-obesity, BMI and dyslipidemia, and could point to a key molecular pathway of metabolic syndrome and its related comorbidities.

Background: This study investigated whether expanding waist circumference (WC) is causally associated with an elevated risk of coronary heart disease (CHD), using a two-sample Mendelian randomization (MR) study through integrating summarized data from genome-wide association study., Methods: The data included in this analysis were mainly from the Genetic Investigation of ANthropometric Traits (GIANT), Consortium and Coronary Artery Disease Genome wide Replication, and Meta-analysis plus the Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) Consortium. Three statistical approaches, inverse-variance weighted (IVW), weighted median, and MR-Egger regression method were conducted to assess the casual relationship. The exposure was WC, measured by 46 single-nucleotide polymorphisms from GIANT and the outcome was the risk of CHD. Then, we used the genetic data from Neale Lab and TAG to infer whether WC causally affected the established risk factors of CHD., Results: The IVW method presented that genetically predicted WC was positively casually associated with CHD (odds ratio [OR]: 1.57, 95% CI = 1.33-1.84; p = 4.81e-08), which was consistent with the result of weighted median and MR-Egger regression. MR-Egger regression indicated that there was no directional horizontal pleiotropy to violate the MR assumption. Additionally, expanded WC was also associated with higher risk of hypertension and diabetes, higher cholesterol, more smoking intensity, and decreased frequency of physical activity., Conclusion: Our analysis provided strong evidence to indicate a causal relationship between WC and increased risk of CHD., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Purpose of Review: Our review provides a brief summary of the most recent advances towards the identification of the genetic basis of specific aspects of obesity and the quantification of their consequences on health. We also highlight the most promising avenues to be explored in the future., Recent Findings: While obesity has been demonstrated to lead to adverse cardio-metabolic consequences, the determinants of inter-individual variability remain largely unknown. The elucidation of the molecular underpinnings of this relationship is hampered by the extremely heterogeneous nature of obesity as a human trait. Recent technological advances have facilitated a more in-depth characterization of body composition at large-scale. At the pace of current data acquisition and resolution, it is realistic to improve characterization of obesity and to advise individuals based on detailed body composition combined with tissue-specific molecular signatures. Individualized predictions of health implications would enable more personalized and effective public health interventions.

Objective: The role of genetic factors in the development of obesity is largely unreported in Sri Lankans. The Q223R (rs1137101) single nucleotide polymorphism (SNP) of the leptin receptor (LEPR) gene has been associated with obesity measures in various ethnicities. We investigated the association of the Q223R polymorphism with obesity related anthropometric measures and biochemical parameters fasting blood glucose and lipid profile in a sample of 530 Sri Lankan adult subjects (age 18-70 years) representing both urban and rural areas of residence., Results: The LEPR Q223R variant G allele frequency was 0.54. The polymorphism was associated with body mass index (p = 0.04) and waist circumference (p = 0.02) measures in overweight and obese (BMI ≥ 25 kgm -2 ) subjects with the variant allele conferring a greater risk of adiposity. Residency in urban areas eliminated the protective effect of the non-risk genotype (AA) in the development of obesity.

Background: DNA methylation is associated with non-communicable diseases (NCDs) and related traits. Methylation data on continental African ancestries are currently scarce, even though there are known genetic and epigenetic differences between ancestral groups and a high burden of NCDs in Africans. Furthermore, the degree to which current literature can be extrapolated to the understudied African populations, who have limited resources to conduct independent large-scale analysis, is not yet known. To this end, this study examines the reproducibility of previously published epigenome-wide association studies of DNA methylation conducted in different ethinicities, on factors related to NCDs, by replicating findings in 120 South African Batswana men aged 45 to 88 years. In addition, novel associations between methylation and NCD-related factors are investigated using the Illumina EPIC BeadChip., Results: Up to 86% of previously identified epigenome-wide associations with NCD-related traits (alcohol consumption, smoking, body mass index, waist circumference, C-reactive protein, blood lipids and age) overlapped with those observed here and a further 13% were directionally consistent. Only 1% of the replicated associations presented with effects opposite to findings in other ancestral groups. The majority of these inconcistencies were associated with population-specific genomic variance. In addition, we identified eight new 450K array CpG associations not previously reported in other ancestries, and 11 novel EPIC CpG associations with alcohol consumption., Conclusions: The successful replication of existing EWAS findings in this African population demonstrates that blood-based 450K EWAS findings from commonly investigated ancestries can largely be extrapolated to ethnicities for which epigenetic data are not yet available. Possible population-specific differences in 14% of the tested associations do, however, motivate the need to include a diversity of ethnic groups in future epigenetic research. The novel associations found with the enhanced coverage of the Illumina EPIC array support its usefulness to expand epigenetic literature.

Acute coronary syndrome occurs when the heart muscle does not receive adequate oxygen and nutrients in a timely manner. Acute coronary syndromes are primarily due to atherosclerosis of the coronary arteries, i.e., coronary heart disease. Nitric oxide (NO) is synthesised from L-arginine in endothelial cells by the constitutive calcium-calmodulin-dependent enzyme, nitric oxide synthase (NOS), which mediates endothelium-dependent vasodilatation. Endothelial nitric oxide synthase (eNOS) is predominantly expressed in endothelial cells. Three NOS isoforms have been detected in different tissue: (1) neuronal NOS (nNOS) (NOS1), (2) eNOS (NOS2), and (3) inducible NOS (iNOS) (NOS3). These isoforms are encoded by three different genes. NOS3 is located on chromosome 7q35-36 and contains 26 exons. Previous studies have suggested that NOS3 polymorphisms may be associated with acute coronary syndromes. Therefore, the aim of the study was to examine the associations between NOS3 rs1799983 (894G/T)andrs2070744 (-786T/C) polymorphisms and unstable angina. This study included 246 patients with unstable angina, as confirmed by coronary angiography. We also included 189 healthy controls who were also assessed by this technique. There were no significant differences in genotype distributions of NOS3 rs1799983and rs2070744 polymorphisms in patients with unstable angina and healthy controls in both univariate and multivariate analyses. In patients with the NOS3 rs1799983 TT genotype, we observed a higher BMI (TT vs. GT + GG, p = 0.068), and in patients with the NOS3 rs2070744 TT genotype, we observed a higher waist circumference (TT vs. TC + CC, p = 0.023; TT vs. CC, p = 0.0053). These data suggest a lack of association between the NOS3 rs1799983andrs2070744 polymorphisms and unstable angina in our patient population. However, these polymorphisms may be associated with some obesity parameters, rs1799983 in females and rs2070744 in males., (© 2020 S. Karger AG, Basel.)

The group-specific component (GC) gene, one of the vitamin D pathway genes, seems to play an important role in cancer development. A population-based breast cancer study including 818 cases and 935 controls in a Chinese population was carried out to evaluate the potential associations of four polymorphisms (rs16847024, rs17467825, rs2298850, and rs3755967) in the GC gene with risk of breast cancer. We detected three SNPs with statistically significant effects on breast cancer development after adjusting for age, menopausal status, body mass index (BMI), family history of breast cancer, income, waist circumference, and education (rs17467825: adjusted OR = 0.80, 95% CI = 0.65-0.99; rs2298850: adjusted OR = 0.80, 95% CI = 0.65-0.98; rs3755967: adjusted OR = 0.80, 95% CI = 0.65-0.98). Stratified analysis found that when an individual had a waist circumference <80 cm, rs17467825, rs2298850, and rs3755967 could markedly reduce the risk of breast cancer. Significant interactions between polymorphisms of rs2298850 and rs3755967 and waist circumference were also observed for breast cancer risk. Combined analysis revealed a significant association among the allele numbers of protective effects with decreased breast cancer risk ( P trend =0.043). These results indicated that, in the GC gene, genetic mutations might be related to breast cancer susceptibility in Chinese women., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2019 Fuxing Chen et al.)

Objective: To determine the frequency of 34 Cytosine >Guanine (proline 12 alanine) variant of peroxisome proliferator activated receptor gamma, and to associate it with metabolic syndrome, insulin resistance and anthropometric obesity parameters., Methods: The cross-sectional comparative study was conducted at the University of Health Sciences, Lahore, Pakistan, from September 2016 to 2017, and comprised patients of metabolic syndrome and healthy controls. Blood pressure and anthropometric measurements of all the subjects were recorded. Fasting blood sample of 4ml was taken for biochemical parameter and deoxyribonucleic acid extraction. The frequency of genetic variant was determined by amplification refractory mutation system polymerase chain reaction. Data was analysed using SPSS 22., Results: Out of 400 subjects, 200 (50%) each were patients and controls. Overall, there were 308 (77%) males and 92 (23%) females. Patients had significantly higher blood pressure, body mass index, waist circumference, waist-to-hip ratio, mid-arm circumference and triceps skinfold thickness compared to the controls (p<0.0001). Insulin resistance was also significantly higher in the patients (p<0.0001) and showed significant correlation with body mass index, waist circumference, waist-to-hip ratio, mid-arm circumference and triceps skinfold thickness (p<0.05).Waist circumference and triceps skinfold thickness were significant predictors of homeostatic model assessment for insulin resistance. Overall, the frequency of homozygous dominant genotype CC of PPAR2 34C>G was 291 (72.75%), heterozygous CG was 93 (23.25%) and homozygous recessive GG was 16 (4%).There was no significant difference in frequency of genotypes between the groups (p=0.216). However, waist circumference and body mass index were significantly lower in GG genotype compared to the CC (p=0.006 versus p=0.02)., Conclusions: Waist circumference and triceps skinfold thickness were found to be the significant predictors of homeostatic model assessment for insulin resistance, while no association was found between 34 C>G variant of peroxisome proliferator activated receptor gamma and metabolic syndrome.

Obesity is a worldwide health problem that is closely linked to many metabolic disorders. Regular physical exercise has been found to attenuate the genetic predisposition to obesity. However, it remains unknown what kinds of exercise can modify the genetic risk of obesity. This study included 18,424 unrelated Han Chinese adults aged 30-70 years who participated in the Taiwan Biobank (TWB). A total of 5 obesity measures were investigated here, including body mass index (BMI), body fat percentage (BFP), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). Because there have been no large genome-wide association studies on obesity for Han Chinese, we used the TWB internal weights to construct genetic risk scores (GRSs) for each obesity measure, and then test the significance of GRS-by-exercise interactions. The significance level throughout this work was set at 0.05/550 = 9.1x10-5 because a total of 550 tests were performed. Performing regular exercise was found to attenuate the genetic effects on 4 obesity measures, including BMI, BFP, WC, and HC. Among the 18 kinds of self-reported regular exercise, 6 mitigated the genetic effects on at least one obesity measure. Regular jogging blunted the genetic effects on BMI, BFP, and HC. Mountain climbing, walking, exercise walking, international standard dancing, and a longer practice of yoga also attenuated the genetic effects on BMI. Exercises such as cycling, stretching exercise, swimming, dance dance revolution, and qigong were not found to modify the genetic effects on any obesity measure. Across all 5 obesity measures, regular jogging consistently presented the most significant interactions with GRSs. Our findings show that the genetic effects on obesity measures can be decreased to various extents by performing different kinds of exercise. The benefits of regular physical exercise are more impactful in subjects who are more predisposed to obesity., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Background: genetic variants of the FTO gene confer the highest risk of obesity identified so far. Associations between the FTO gene and alterations in metabolic markers have been reported in different populations but not in Chileans. The aim of this study was therefore to investigate the association of rs3751812 gene polymorphism with adiposity and metabolic markers in the Chilean adult population. Methods: genotype of the FTO gene was determined in 409 participants from the GENADIO study. Adiposity markers (body weight, BMI, % fat mass and waist circumference), metabolic markers (glycemia, insulin, HOMAIR, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, leptin, ALT, GGT, PCRhs) and blood pressure were measured. The association between the FTO genotype and the different markers was determined using linear regression analyses. Results: there was an association between the polymorphism and all adiposity markers as well as insulin, HOMAIR, leptin and HDL cholesterol (p < 0.05) in the fully adjusted model. For total cholesterol, triglycerides, LDL cholesterol, ALT, GGT and PCRhs, the association disappeared after adjustment by body mass index. Conclusion: our findings verify the association between the FTO rs3751812 polymorphism with obesity, hyperinsulinemia, hyperleptinemia and lower levels of HDL cholesterol in the Chilean population. These alterations could increase the risk of diabetes mellitus type II and metabolic syndrome.

The present study investigated whether dietary patterns could interact with fat mass and obesity-associated (FTO) polymorphisms in relation to changes in BMI and waist circumference (WC) over 3⋅6 years of follow-up. Subjects were selected from participants of the Tehran Lipid and Glucose Study (n 4292, 43⋅2 % male). Dietary data were collected using a valid and reliable FFQ. Dietary patterns were determined using factor analysis. The genotypes of polymorphisms (rs1421085, rs1121980, rs17817449, rs8050136, rs9939973 and rs3751812) were determined. Genetic risk score (GRS) was calculated using the weighted method. Mean ages of men and women were 42·6 (sd 14) and 40⋅4 (sd 13) years, respectively. The healthy (e.g. vegetables and fruits) and the Western dietary patterns (WDP; e.g. soft drinks and fast foods) were extracted. In carriers of the risk alleles rs1121980, rs1421085, rs8050136, rs1781799 and rs3751812, BMI was approximately 2-fold higher in individuals in the higher quartile of WDP score, compared with the first quartile (P &lt; 0⋅05). WC increased with increasing WDP score in carriers of the risk alleles rs1121980 and rs3751812, but not in individuals who did not carry any risk alleles. BMI and WC increased to a greater extent in the high GRS group while increasing quartiles of the WDP score, compared with the low GRS group (BMI change; Q1: 1⋅04 (se 0⋅34) v. Q4: 2⋅26 (se 0⋅36)) (WC change; Q1: 0⋅47 (se 0⋅32) v. Q4: 0⋅95 (se 0⋅34)) (P interaction &lt; 0⋅05). These results suggest that adults with higher genetic predisposition to obesity are more susceptible to the harmful effects of adherence to the WDP, which emphasised the need to reduce the consumption of unhealthy foods for the prevention of obesity.

Objectives: The role of ADIPOQ gene variants on weight loss after a dietary intervention remain unclear. The aim of this study was to analyze the effects of rs266729 of the ADIPOQ gene on cardiovascular risk factors and adiposity parameters after adherence to a Mediterranean-type hypocaloric diet., Method: Eighty-three obese patients were studied before and after 12 wk on a Mediterranean-type hypocaloric diet. Anthropometric parameters and biochemical profiles were measured. The variant of ADIPOQ gene rs266729 was assessed at basal time by polymerase chain reaction at real time., Results: Two genotype groups were realized (CC versus CG + GG). The final genotype distribution was 48 patients CC (57.8%), 30 patients CG (36.2%) and 5 patients GG (6%). After dietary intervention with a moderate calorie restriction and in both genotypes, body mass index (BMI), weight, fat mass, systolic blood pressure, and waist circumference decreased. After dietary intervention and in non-G allele carriers (CC versus CG+ GG), glucose (δ: -6.2 ± 1.1 versus -2.9 ± 1.2 mg/dL; P = 0.02), total cholesterol (δ:-15.2 ± 3.1 versus -3.4 ± 2 mg/dL; P = 0.02), low-density lipoprotein cholesterol (δ, -14.9 ± 3.1 versus -4.9 ± 1.2 mg/dL; P = 0.01), insulin levels (δ, -4± 0.6 versus 0.7 ± 0.3 UI/L;P = 0.01), homeostasis model assessment for insulin resistance (δ, -1.6 ± 0.4 versus -0.2 ± 0.4 units; P = 0.01), and adiponectin (δ, -10.4 ± 3.1 versus -1.3 ± 1.0 ng/dL; P = 0.01) improved., Conclusion: After weight loss, the CC genotype of ADIPOQ gene variant (rs266729) is associated with increases in adiponectin levels and decreases of low-density lipoprotein cholesterol, insulin and homeostasis model assessment for insulin resistance after weight loss., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The Gln233Arg (A>G; rs1137101) polymorphism of the leptin receptor gene (LEPR) has been investigated extensively and is reported to be associated with different metabolic states. In this investigation, we aimed to study the frequency of Gln233Arg genotypes and alleles in a group of Saudi women stratified by their body mass index (BMI), to correlate the LEPR genotypes with variations in anthropometric, lipid and hormonal parameters and to investigate conformational and structural variations in the mutant LEPR using molecular dynamic (MD) investigations. The study group included 122 Saudi women (normal weight = 60; obese = 62) attending the clinics for a routine checkup. Anthropometric data: height, weight, waist and hip circumference were recorded and fasting serum sample was used to estimate glucose, lipids, ghrelin, leptin and insulin. BMI, W/H ratio, and HOMA-IR values were calculated. Whole blood sample was used to extract DNA; exon 6 of the LEPR gene was amplified by PCR and sequencing was conducted on an ABI 3100 Avant Genetic Analyser. Molecular Dynamic Simulation studies were carried out using different softwares. The results showed the presence of all three genotypes of Gln233Arg in Saudi women, but the frequencies were significantly different when compared to reports from some populations. No differences were seen in the genotype and allele frequencies between the normal weight and obese women. Stratification by the genotypes showed significantly higher BMI, waist and hip circumference, leptin, insulin, fasting glucose and HOMA-IR and lower ghrelin levels in obese women carrying the GG genotype. Even in the normal weight group, individuals with GG genotype had higher BMI, waist and hip circumference and significantly lower ghrelin levels. The MD studies showed a significant effect of the Gln/Arg substitution on the conformation, flexibility, root-mean-square fluctuation (RMSF), radius of gyration (Rg) values, solvent-accessible surface area (SASA) and number of inter- and intra-molecular H-bonds. The results suggest that the structural changes brought about by the mutation, influence the signaling pathways by some unknown mechanism, which may be contributing to the abnormalities seen in the individuals carrying the G allele of rs1137101., Competing Interests: The authors have declared that no competing interests exist.

Background & Aims: A G-to-A transition located 75 base pairs upstream (rs670) from transcription start site of the APOA1 gene is related with metabolic parameters. The aim of the present investigation was to describe the association of rs670 with metabolic syndrome and metabolic parameters., Methods: The study involved a population of 1000 obese subjects. Measurements of anthropometric parameters, arterial blood pressure, fasting blood glucose, C-reactive protein (CRP), insulin concentration, insulin resistance (HOMA-IR), lipid profile, adipokines levels and prevalence of MetS was recorded. Genotype of ApoA1 gene polymorphism (rs670) was evaluated., Results: A sample of 1000 obese subjects with a mean BMI of 36.5 ± 5.0 kg/m 2 was enrolled. In males, weight (delta: 3.3 ± 1.2 kg; p = 0.01), fat mass (delta: 2.7 ± 1.1 kg; p = 0.01), waist circumference (delta: 2.8 ± 1.1 cm; p = 0.02), fasting glucose (delta: 8.9 ± 2.2 mg/dl; p = 0.01), insulin levels (delta: 3.7 ± 1.2 UI/L; p = 0.04) and HOMA-IR (delta: 1.2 ± 1.1 units; p = 0.02) were higher in non-A allele carriers than A allele carriers. In males without A allele, an increased risk of hyperglycemia (OR = 1.40, 95% CI = 1.09-2.09, p = 0.04), percentage of central obesity (OR = 4.55, 95% CI = 1.36-15.39, p = 0.01), percentage of low HDL-C (OR = 2.02, 95% CI = 1.02-4.03, p = 0.03) and prevalence of diabetes mellitus (OR = 2.14, 95% CI = 1.03-5.04, p = 0.03) were reported., Conclusions: rs670 of APOA1 gene has a gender specific influence on serum glucose, insulin, HOMA-IR, fat mass, weight and waist circumference. Males without A allele showed high rates of central obesity, low levels of HDL, hyperglycemia and diabetes mellitus., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Obesity is more prevalent in men than in women in China, especially within the middle-aged population., Objectives: The present study aims to determine the contribution of sexual dimorphisms to obesity and related traits in terms of the mechanisms involving the obesity-related genetic variants among patients of Chinese Han ancestry with type 2 diabetes., Method: In the Chinese National Diabetes and Metabolic Disorders Study, 2,555 out of 4,036 patients with type 2 diabetes were treatment naive, including 1,142 men and 1,413 women. Single-nucleotide polymorphisms (SNP) from 18 genomic loci previously found to be associated with obesity-related traits were successfully genotyped, and a genetic risk score (GRS) was constructed by summing the risk alleles for obesity., Results: Single SNP analysis showed that genetic variants in SLC30A10, TMEM18, GNPDA2, PRL, TFAP2B, BDNF, MTCH2, FTO, and MC4R were nominally associated with waist circumference (WC), BMI, and risk for abdominal or general obesity in the untreated patients with type 2 diabetes, as well as in the total group of patients with type 2 diabetes (untreated and treated) (p < 0.05). Interactions between sex and SNP in PRL, MTCH2,and FTO were detected (p < 0.05). In the untreated patients with diabetes, the GRS was nominally associated with WC (β = 0.0032, SE = 0.0011; p = 0.003), BMI (β = 0.0030, SE = 0.0013; p = 0.027), and increased risk for abdominal (OR = 1.08; 95% CI 1.02-1.13; p = 0.004) or general obesity (OR = 1.07; 95% CI 1.02-1.13; p = 0.011) in men but not in women. GRS-sex interactions were detected in the determinant of WC (p = 0.019) and abdominal obesity (p = 0.016). Among patients aged 30-60 years, GRS was found to be significantly associated with WC (β = 0.0050, SE = 0.0016; p = 0.002) and abdominal obesity (OR = 1.10; 95% CI 1.04-1.17; p = 0.001) and nominally associated with BMI (β = 0.0057, SE = 0.0020; p = 0.005) and general obesity (OR = 1.07; 95% CI 1.01-1.14; p = 0.027) in men, whereas in women none of the associations were detected. GRS-sex interactions were present in the determinant of WC (p = 0.015), BMI (p = 0.032), and abdominal obesity (p = 0.012). Among patients aged 60 years or older, neither an association of GRS with obesity-related traits nor GRS-sex interactions were detected., Conclusions: Genetic factors contribute to obesity-related traits in a sex-dependent pattern among middle-aged Chinese, and men tend to be more susceptible to the genetic risk of obesity., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

The prevalence of childhood obesity has increased worldwide. Although it is considered a polygenic inheritance disease, little is known about its susceptibility when the additive effect is considered. The aim of this study is to investigate whether the genetic risk score (GRS) based on previously associated obesity polymorphisms (SNP) rs9939609 (fat mass and obesity-associated (FTO)), rs6548238 (transmembrane protein 18 (TMEM18)) and rs16835198 (fibronectin type III domain containing 5 (FNDC5)) could serve as a predictor for anthropometric characteristics in a sample of Brazilian children and adolescents. This is a cross-sectional study with 1471 children and adolescents aged 6-17 years. BMI, waist circumference (WC) and percentage of body fat and metabolic parameters were verified. In all, three SNP were genotyped by TaqMan™ allelic discrimination. The metabolic and anthropometric parameters were compared between the genotypes, and the unweighted and weighted GRS (GRS and wGRS, respectively) were created to test the additive effect of these genetic polymorphisms on anthropometric parameters. The prevalence of overweight plus obesity was 41 %. Significant associations were identified for FTO rs9939609, TMEM18 rs6548238 and FNDC5 rs16835198 and for GRS and wGRS with anthropometric phenotypes. The higher score of wGRS was associated with obesity (OR: 2·65, 95 % CI 1·40, 5·04, P=0·003) and with greater WC (OR: 2·91, 95 % CI 1·57, 5·40, P=0·001). Our results suggest that these genetic variants contribute to obesity susceptibility in children and adolescents and reinforce the idea that the additive effect may be useful to elucidate the genetic component of obesity.

Background: The correlation between single nucleotide polymorphisms (SNPs) of milk fat globule-epidermal growth factor 8 (MFGE8) and metabolic syndrome (MetS) and metabolism-related indicators are limited. The present study explored the relation in Chinese adults., Methods: We conducted a nested case-control study based on the Rural Chinese Cohort Study including 408 people with MetS and 408 controls matched by baseline sex, age (±2 years), marital status, and residence village. Four polymorphisms were selected and genotyped by using the SNPscan Genotyping system. Conditional logistic regression was used to estimate the association of MFGE8 polymorphisms with MetS incidence, and linear regression was used to assess the association with metabolism-related indicators in controls., Results: We found no significant association of MFGE8 SNPs with MetS incidence or systolic blood pressure, or triglycerides level, or fasting plasma glucose (P > 0.05). However, MFGE8 rs4932450 was negatively associated with high-density lipoprotein cholesterol (HDL-C) level under the dominant model (β = -0.0218, P = 0.007) and the additive model (β = -0.0175, P = 0.012) and positively associated with diastolic blood pressure (DBP) under the recessive model (β = 4.8848, P = 0.011). The rs3784751 SNP was associated with increased waist circumference (WC) in controls (β = 0.0307, P = 0.028)., Conclusions: MFGE8 polymorphisms were not associated with MetS but were related to DBP, HDL-C level, and WC in Chinese adults., (Copyright © 2018 Elsevier B.V. All rights reserved.)