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Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in European-ancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3 , CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.
The genetic background of general obesity and fat distribution is different, pointing to separate underlying physiology. Here, we searched for metabolites and lipoprotein particles associated with fat distribution, measured as waist/hip ratio adjusted for fat mass (WHRadjfatmass), and general adiposity measured as percentage fat mass.
Hypertension is a public health issue touted as a "silent killer" worldwide. The present study aimed to explore the sex differential in the association of anthropometric measures including body mass index, waist circumference, and waist-hip ratio with hypertension among older adults in India. The study used data from the Longitudinal Aging Study in India (LASI) conducted during 2017-18. The sample contains 15,098 males and 16,366 females aged 60 years and above. Descriptive statistics (percentages) along with bivariate analysis were presented. Multivariable binary logistic regression analyses were used to examine the associations between the outcome variable (hypertension) and putative risk or protective factors. About 33.9% of males and 38.2% of females aged 60 years and above suffered from hypertension. After adjusting for the socioeconomic, demographic and health-behavioral factors, the odds of hypertension were 1.37 times (CI: 1.27-1.47), significantly higher among older adults who were obese or overweight than those with no overweight/obese condition. Older adults with high-risk waist circumference and waist-hip ratio had 1.16 times (CI: 1.08-1.25) and 1.42 times (CI: 1.32-1.51) higher odds of suffering from hypertension, respectively compared to their counterparts with no high-risk waist circumference or waist-hip ratio. The interaction effects showed that older females with overweight/obesity [OR: 0.84; CI: 0.61-0.74], high-risk waist circumference [OR: 0.89; CI: 0.78-0.99], and high-risk waist-hip ratio [OR: 0.90; CI: 0.83-0.97] had a lower chance of suffering from hypertension than their male counterparts with the similar anthropometric status. The findings suggested a larger magnitude of the association between obesity, high-risk waist circumference, high-risk waist-hip ratio and prevalent hypertension among older males than females. The study also highlights the importance of measuring obesity and central adiposity in older individuals and using such measures as screening tools for timely identification of hypertension.
Several studies have identified that obesity and being overweight can increase the risk of developing myocardial infarction (MI). However, the predictive value of the central obesity index, that is, the waist-hip ratio (WHR), regarding MI risk remains unclear. This study aimed to provide a systematic review and meta-analysis of WHR as a predictor of MI incidence.
We combined CAGE sequencing in human adipocytes during differentiation with data from genome-wide association studies to identify an enhancer in the SNX10 locus on chromosome 7, presumably involved in body fat distribution. Using reporter assays and CRISPR-Cas9 gene editing in human cell lines, we characterized the role of the enhancer in adipogenesis. The enhancer was active during adipogenesis and responded strongly to insulin and isoprenaline. The allele associated with increased waist-hip ratio in human genetic studies was associated with higher enhancer activity. Mutations of the enhancer resulted in less adipocyte differentiation. RNA sequencing of cells with disrupted enhancer showed reduced expression of established adipocyte markers, such as ADIPOQ and LPL, and identified CHI3L1 on chromosome 1 as a potential gene involved in adipocyte differentiation. In conclusion, we identified and characterized an enhancer in the SNX10 locus and outlined its plausible mechanisms of action and downstream targets.
This study aimed to identify the non-linear association between population density and obesity in China and to provide empirical evidence for the public health orientated guideline of urban planning. By conducting a longitudinal study with data collected from the China Health and Nutrition Survey (CHNS) between 2004 and 2011, we applied fixed-effect models to assess the non-linear association between the compact built environment and waist-hip ratio (WHR), controlling for sex, age, nationality, education, employment status, marital status, household size, household income, and residents' attitudes. Our findings reveal that the built environment is one of the key determinants of obesity. The U-shaped influence of population density on WHR was observed. Moreover, influence differs according to sex and weight status. Our findings indicate healthy city planning has the potential to improve the built environment to reduce obesity risk and promote public health.
The association of abdominal obesity with cardiovascular risk is often linked to altered secretion of adipose-derived factors and an abnormal lipid profile including formation of atherogenic small dense low density lipoprotein particles (sdLDL). Acylation-stimulating protein (ASP) is an adipose-derived hormone that exhibits potent lipogenic effects. Plasma ASP levels increase in obesity; however, the association of ASP levels with body fat distribution is not yet established, and no study to date has investigated the association of ASP with LDL size. In this study, we examined the association of ASP levels with abdominal obesity measures and the lipid profile including LDL size in 83 men with a wide range of abdominal girths. Regression analysis showed that waist/hip ratio was the main predictor of ASP levels ( β = 0.52, P < 0.0001), significantly followed by decreased LDL size. BMI and TG levels, although positively correlated with ASP levels, were excluded as significant predictors in regression analysis. No correlation was found with LDL-C or apoB levels. ASP levels were 62.5% higher in abdominally obese compared to nonobese men. Waist/hip ratio presenting as the main predictor of ASP levels, suggests increased ASP production by abdominal fat which, as proposed previously, may result from resistance to ASP function causing delayed TG clearance and subsequent formation of atherogenic sdLDL.
We analyze how measures of adiposity - body mass index (BMI) and waist hip ratio (WHR) - causally influence rates of hospital admission. Conventional analyses of this relationship are susceptible to omitted variable bias from variables that jointly influence both hospital admission and adipose status. We implement a novel quasi-Poisson instrumental variable model in a Mendelian randomization framework, identifying causal effects from random perturbations to germline genetic variation. We estimate the individual and joint effects of BMI, WHR, and WHR adjusted for BMI. We also implement multivariable instrumental variable methods in which the causal effect of one exposure is estimated conditionally on the causal effect of another exposure. Data on 310,471 participants and over 550,000 inpatient admissions in the UK Biobank were used to perform one-sample and two-sample Mendelian randomization analyses. The results supported a causal role of adiposity on hospital admissions, with consistency across all estimates and sensitivity analyses. Point estimates were generally larger than estimates from comparable observational specifications. We observed an attenuation of the BMI effect when adjusting for WHR in the multivariable Mendelian randomization analyses, suggesting that an adverse fat distribution, rather than a higher BMI itself, may drive the relationship between adiposity and risk of hospital admission.
The meta-analyses of genome-wide association studies identified several waist-hip ratio (WHR) related loci in individuals of European ancestry. Since the pattern of fat distribution and the relationship between fat distribution and glucose metabolism disturbance in Chinese are different from those in Europeans, the present study aimed to explore the individual and cumulative effects of WHR-related loci on glycemic phenotypes in Chinese children.
Glycosylated hemoglobin (HbA1c) reflects the average blood sugar over the past eight to twelve weeks. Several demographic and lifestyle factors are known to affect HbA1c levels. We evaluated the association of HbA1c with aerobic and resistance exercise in non-diabetic Taiwanese adults based on the waist-hip ratio (WHR).
We have prioritised a single nucleotide polymorphism (SNP) rs2645294 as one candidate functional SNP in the TBX15-WARS2 waist-hip-ratio locus using posterior probability analysis. This SNP is located in the 3' untranslated region of the WARS2 (tryptophanyl tRNA synthetase 2, mitochondrial) gene with which it has an expression quantitative trait in subcutaneous white adipose tissue. We show that transcripts of the WARS2 gene in a human white adipose cell line, heterozygous for the rs2645294 SNP, showed allelic imbalance. We tested whether the rs2645294 SNP altered WARS2 RNA stability using three different methods: actinomycin-D inhibition and RNA decay, mature and nascent RNA analysis and luciferase reporter assays. We found no evidence of a difference in RNA stability between the rs2645294 alleles indicating that the allelic expression imbalance was likely due to transcriptional regulation.
The relationship between obesity indices and arterial stiffness (AS) has not been fully discovered nor has it been studied in depth in large hypertensive patient populations. The aim of this study was to explore the association between body mass index (BMI) and waist-hip ratio (WHR) levels and AS based on brachial-ankle pulse wave velocity (baPWV) in Chinese rural adults with hypertension.
Neck circumference (NC) is an attractive method for determining overweight and obesity in school age children because it is inexpensive and culturally acceptable. However, this technique has not been assessed for its accuracy in school children from countries of the Gulf Cooperation Council, which have high prevalence of overweight and obesity.The aim of this preliminary study was to investigate the correlation between the body mass index (BMI), NC, and waist-hip ratio and demographic characteristics among 10- to 18-year-old adolescent school children in Bahrain.BMI was calculated using Center of Disease Control and Prevention Children's BMI Tool for Schools. Data was collected for a total of n = 397 adolescents from 4 different private schools with an average age of 12.91 years; 57.7% were male and 42.3% female.In this sample of adolescents, 50.1% were either overweight (21.4%) or obese (28.7%). BMI was significantly associated with waist-hip ratio (P < .01), gender (P < .05), and age (P < .01). Multiple linear regressions revealed that NC was significantly associated with age (P < .001) and less so with gender (P = .071) and BMI was significantly associated with NC (P < .01), gender (P < .01), and age (P < .05). Analysis of the receiver operating characteristic for males and females combined showed fair sensitivity and specificity (Area under the curve (AUC) = 0.707; 95% CI: 0.656, 0.758).NC is weakly correlated with BMI, and only a fair instrument for identifying overweight/obesity based on receiver operating characteristic curve analysis. Therefore, NC could only be used as an adjunct screening tool for weight status in this sample.
Obesity is a consideration in the pharmacologic intervention for estrogen receptor (ER) positive (ER+) breast cancer risk. Body mass index (BMI) and waist/hip ratio (WHR) have demonstrated different effects on breast cancer risk in relation to estrogen receptor (ER) status, but the results have been inconsistent. Furthermore, the situation in Chinese women remains unclear.
Obesity is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). However, 'obesity paradox' is observed in patients with coronary artery disease while defining obesity by body mass index (BMI). The purpose of this study is to identify a better anthropometric parameter to predict cardiovascular events in patients with ASCVD. The study was conducted using the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. A total of 6,920 adult patients with stable ASCVD, enrolled from January 2010 to November 2014, were included, with a mean age of 65.9 years, 73.9% males, and a mean BMI of 26.3 kg/m2 at baseline. These patients were followed up for a median of 2.5 years. The study endpoint was the composite major adverse cardiovascular event (MACE), defined as cardiovascular death, nonfatal myocardial infarction or stroke, or cardiac arrest with resuscitation. Multivariable Cox proportional hazards regression showed a significant positive association between waist-to-BMI ratio and MACE (adjusted hazard ratio 1.69 per cm‧m2/kg increase in waist-to-BMI ratio, 95% CI 1.12-2.49, p = 0.01) after adjusting for potential risk factors and confounders. Traditional anthropometric parameters, such as BMI, weight, waist and waist-hip ratio, or newer waist-based indices, such as body roundness index and a body shape index, did not show any significant linear associations (p = 0.09, 0.30, 0.89, 0.54, 0.79 and 0.06, respectively). In the restricted cubic spline regression analysis, the positive dose-response association between waist-to-BMI ratio and MACE persisted across all the range of waist-to-BMI ratio. The positive dose-response association was non-linear with a much steeper increase in the risk of MACE for waist-to-BMI ratio > 3.6 cm‧m2/kg. In conclusion, waist-to-BMI ratio may function as a positive predictor for the risk of MACE in established ASCVD patients.
Studies of the relationship between serum 25-hydroxyvitamin D (25(OH)D) and changes in measures of adiposity have shown inconsistent results, and interaction with genetic predisposition to obesity has rarely been examined. We examined whether 25(OH)D was associated with subsequent annual changes in body weight (ΔBW) or waist circumference (ΔWC), and whether the associations were modified by genetic predisposition to a high BMI, WC or waist-hip ratio adjusted for BMI (WHRBMI). The study was based on 10,898 individuals from the Danish Inter99, the 1958 British Birth Cohort and the Northern Finland Birth Cohort 1966. We combined 42 adiposity-associated Single Nucleotide Polymorphisms (SNPs) into four scores indicating genetic predisposition to BMI, WC and WHRBMI, or all three traits combined. Linear regression was used to examine the association between serum 25(OH)D and ΔBW or ΔWC, SNP-score × 25(OH)D interactions were examined, and results from the individual cohorts were meta-analyzed. In the meta-analyses, we found no evidence of an association between 25(OH)D and ΔBW (-9.4 gram/y per 10 nmol/L higher 25(OH)D [95% CI: -23.0, +4.3; P = 0.18]) or ΔWC (-0.06 mm/y per 10 nmol/L higher 25(OH)D [95% CI: -0.17, +0.06; P = 0.33]). Furthermore, we found no statistically significant interactions between the four SNP-scores and 25(OH)D in relation to ΔBW or ΔWC. Thus, in view of the narrow CIs, our results suggest that an association between 25(OH)D and changes in measures of adiposity is absent or marginal. Similarly, the study provided evidence that there is either no or very limited dependence on genetic predisposition to adiposity.
Cross-sectional data suggests that a low level of plasma ascorbic acid positively associates with both Body Mass Index (BMI) and Waist Circumference (WC). This leads to questions about a possible relationship between dietary intake of ascorbic acid and subsequent changes in anthropometry, and whether such associations may depend on genetic predisposition to obesity. Hence, we examined whether dietary ascorbic acid, possibly in interaction with the genetic predisposition to a high BMI, WC or waist-hip ratio adjusted for BMI (WHR), associates with subsequent annual changes in weight (∆BW) and waist circumference (∆WC).
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