Dataset Information

Detailed Functional Characterization of a Waist-Hip Ratio Locus in 7p15.2 Defines an Enhancer Controlling Adipocyte Differentiation.

ABSTRACT: 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.

SUBMITTER: Castillejo-Lopez C

PROVIDER: S-EPMC6817687 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Detailed Functional Characterization of a Waist-Hip Ratio Locus in 7p15.2 Defines an Enhancer Controlling Adipocyte Differentiation.

Castillejo-Lopez Casimiro C Pjanic Milos M Pirona Anna Chiara AC Hetty Susanne S Wabitsch Martin M Wadelius Claes C Quertermous Thomas T Arner Erik E Ingelsson Erik E

iScience 20190910

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 ra ...[more]

PMID: 31557715

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Project description:BackgroundWaist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) are all independent predictors of cardio-metabolic risk and therefore important in HIV/AIDS patients on antiretroviral therapy at risk of increased visceral adiposity. This study aimed to assess the extent of agreement between these parameters and the body mass index (BMI), as anthropometric parameters and in classifying cardio-metabolic risk in HIV/AIDS patients.MethodsA secondary analysis of data from a cross-sectional study involving 200 HIV/AIDS patients was done. Anthropometric parameters were measured from participants using standard guidelines and central obesity defined according to recommended criteria. Increased cardio-metabolic risk was defined according to the standard cut-off values for all four parameters. Data were analyzed using STATA version 14.1.ResultsThe prevalence of WC-defined central obesity, WHR-defined central obesity and WHtR > 0.50 were 33.5%, 44.5% and 36.5%, respectively. The prevalence of BMI-defined overweight and obesity was 40.5%. After adjusting for gender and HAART status, there was a significant linear association and correlation between WC and BMI (regression equation: WC (cm) = 37.184 + 1.756 BMI (Kg/m2) + 0.825 Male + 1.002 HAART, (p < 0.001, r = 0.65)), and between WHtR and BMI (regression equation: WHtR = 0.223 + 0.011 BMI (Kg/m2)- 0.0153 Male + 0.003 HAART, (p < 0.001, r = 0.65)), but not between WHR and BMI (p = 0.097, r = 0.13). There was no agreement between the WC, WHtR and BMI, and minimal agreement between the WHR and BMI, in identifying patients with an increased cardio-metabolic risk.ConclusionDespite the observed linear association and correlation between these anthropometric parameters, the routine use of WC, WHR and WHtR as better predictors of cardio-metabolic risk should be encouraged in these patients, due to their minimal agreement with BMI in identifying HIV/AIDS patients with increased cardio-metabolic risk. HAART status does not appear to significantly affect the association between these anthropometric parameters.

Project description:BackgroundCentral and general obesity are commonly measured using tools like waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). However, the universally recognized cutoffs for these measures may be inadequate for individuals of Ethiopian descent. Due to the lack of universally applicable cutoffs, studies recommend tailoring the optimal screening thresholds to each population's specific characteristics. Therefore, this study aimed to determine body composition-based WC, WHR, and WHtR cutoffs for the healthy adult population of Ethiopia.MethodA population based cross-sectional study was conducted in the Amhara region of Ethiopia from June to August 2023, collecting anthropometric and body composition data from 838 adult participants. Data were analyzed using Stata, and MedCalc software. The cut-off values were determined using ROC analysis, and performance was assessed using area under the curve (AUC), Youden index, sensitivity, and specificity.ResultThe optimal cut-off values for WC, HC, WHR, and WHtR to define obesity in men were 85.0 cm, 93.5 cm, 0.89, and 0.53 respectively. Correspondingly, these values in women were 81.1 cm, 97.2 cm, 0.84, and 0.5. These cutoff values showed the highest effectiveness in defining obesity especially for WC and WHtR. The new proposed cutoff values for waist circumference, hip circumference, and waist-to-height ratio had sensitivity ranging 76-93% and specificity of 83-94% in accurately identifying obesity. The current study also determined the cut-off values for underweight, normal weight, and overweight body weight categories. Accordingly, for men, the WC cut-offs were: ≤ 74.55 cm (underweight), 74.56-78.95 cm (normal), and 79.0-85.0 cm (overweight). For women, the cut-offs were: ≤ 68.25 cm (underweight), 68.26-79.59 cm (normal), and 79.60-81.10 cm (overweight). The WHtR thresholds were: ≤0.43 (underweight), 0.44-0.47 (normal), and 0.48-0.53 (overweight) in men; ≤0.43 (underweight), 0.44-0.50 (normal), and 0.50-0.51 (overweight) in women.ConclusionThe findings indicate that the WC, WHR, and WHtR cutoff values for defining obesity in Ethiopian adults are lower than international standards. The newly proposed cutoff values showed improved sensitivity and specificity, suggesting their potential diagnostic relevance. Considering these country-specific cutoffs may be beneficial for clinical practice and obesity-related research in Ethiopia.

Project description:BackgroundLittle is known about the long-term shifts in distributions of three abdominal-obesity-related indicators, waist circumference (WC), waist-to-hip ratio (WHpR) and waist-to-height ratio (WHtR) among Chinese adults. Traditional mean regression models used in the previous analyses were limited in their ability to capture cross-distribution among effects. The current study aims to describe the shift in distribution of WC, WHpR, and WHtR over a period of 18 years (1993-2011) in China, and to reveal quantile-specific associations of the three indicators with key covariates.MethodsLongitudinal data from seven waves of the China Health and Nutrition Surveys (CHNS) in 1993, 1997, 2000, 2004, 2006, 2009 and 2011 were analyzed. The LMS method was used to illustrate the gender-specific quantile curves of WC, WHtR and WHpR over age. Separate gender-stratified longitudinal quantile regressions were employed to investigate the effect of important factors on the trends of the three indicators.ResultsA total of 11,923 participants aged 18-65 years with 49,507 observations were included in the analysis. The density curves of WC, WHtR and WHpR shifted to right and became wider. The three outcomes all increased with age and increased more at upper percentiles. From the multivariate quantile regression, physical activity was negatively associated in both genders; smoking only had a negative effect on male indicators. Education and drinking behavior both had opposite effects on the three indicators between men and women. Marital status and income were positively associated with the shifts in WC, WHtR and WHpR in male and female WC, while urbanicity index had a positive effect on three outcomes in men but inconsistent effect among female outcomes.ConclusionsThe abdominal-obesity related indicators of the Chinese adults experienced rapid growth according to our population-based, age- and gender-specific analyses. Over the 18-year study period, major increases in WC, WHtR and WHpR were observed among Chinese adults. Specifically, these increases were greater at upper percentiles and in men. Age, physical activity, energy intake, drinking, smoking, education, income and urbanicity index were associated with elevated abdominal obesity indicators, and the effects differed among percentiles and between genders.

Dataset Information

Detailed Functional Characterization of a Waist-Hip Ratio Locus in 7p15.2 Defines an Enhancer Controlling Adipocyte Differentiation.

Publications

Detailed Functional Characterization of a Waist-Hip Ratio Locus in 7p15.2 Defines an Enhancer Controlling Adipocyte Differentiation.

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