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Genetic Association of Waist-to-Hip Ratio With Cardiometabolic Traits, Type 2 Diabetes, and Coronary Heart Disease.

ABSTRACT: Importance:In observational studies, abdominal adiposity has been associated with type 2 diabetes and coronary heart disease (CHD). Whether these associations represent causal relationships remains uncertain. Objective:To test the association of a polygenic risk score for waist-to-hip ratio (WHR) adjusted for body mass index (BMI), a measure of abdominal adiposity, with type 2 diabetes and CHD through the potential intermediates of blood lipids, blood pressure, and glycemic phenotypes. Design, Setting, and Participants:A polygenic risk score for WHR adjusted for BMI, a measure of genetic predisposition to abdominal adiposity, was constructed with 48 single-nucleotide polymorphisms. The association of this score with cardiometabolic traits, type 2 diabetes, and CHD was tested in a mendelian randomization analysis that combined case-control and cross-sectional data sets. Estimates for cardiometabolic traits were based on a combined data set consisting of summary results from 4 genome-wide association studies conducted from 2007 to 2015, including up to 322?154 participants, as well as individual-level, cross-sectional data from the UK Biobank collected from 2007-2011, including 111?986 individuals. Estimates for type 2 diabetes and CHD were derived from summary statistics of 2 separate genome-wide association studies conducted from 2007 to 2015 and including 149?821 individuals and 184?305 individuals, respectively, combined with individual-level data from the UK Biobank. Exposures:Genetic predisposition to increased WHR adjusted for BMI. Main Outcomes and Measures:Type 2 diabetes and CHD. Results:Among 111?986 individuals in the UK Biobank, the mean age was 57 (SD, 8) years, 58?845 participants (52.5%) were women, and mean WHR was 0.875. Analysis of summary-level genome-wide association study results and individual-level UK Biobank data demonstrated that a 1-SD increase in WHR adjusted for BMI mediated by the polygenic risk score was associated with 27-mg/dL higher triglyceride levels, 4.1-mg/dL higher 2-hour glucose levels, and 2.1-mm Hg higher systolic blood pressure (each P?

SUBMITTER: Emdin CA

PROVIDER: S-EPMC5571980 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Genetic Association of Waist-to-Hip Ratio With Cardiometabolic Traits, Type 2 Diabetes, and Coronary Heart Disease.

Emdin Connor A CA Khera Amit V AV Natarajan Pradeep P Klarin Derek D Zekavat Seyedeh M SM Hsiao Allan J AJ Kathiresan Sekar S

JAMA 20170201 6

<h4>Importance</h4>In observational studies, abdominal adiposity has been associated with type 2 diabetes and coronary heart disease (CHD). Whether these associations represent causal relationships remains uncertain.<h4>Objective</h4>To test the association of a polygenic risk score for waist-to-hip ratio (WHR) adjusted for body mass index (BMI), a measure of abdominal adiposity, with type 2 diabetes and CHD through the potential intermediates of blood lipids, blood pressure, and glycemic phenot ...[more]

PMID: 28196256

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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:Background Childhood overweight/obesity has been associated with an elevated risk of insulin resistance and cardiometabolic disorders. Waist-to-height ratio (WHtR) may be a simple screening tool to quickly identify children at elevated risk for cardiometabolic disorders. The primary objective of the present study was to create sex-specific tertile cut points of WHtR and assess its association with Insulin resistance and elevated liver enzyme concentrations in children, factors using cross-sectional data from the randomized, controlled Family Weight Management Study. Methods Baseline data from 360 children (7–12 years, mean Body Mass Index (BMI) ≥ 85th percentile for age and sex) were used to calculate WHtR tertiles by sex, male: ≤ 0.55 (T1), > 0.55- ≤ 0.59 (T2), > 0.59 (T3); female: ≤ 0.56 (T1), > 0.56- ≤ 0.6 (T2), > 0.6 (T3). The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was used to categorize participants as insulin-resistant (HOMA-IR ≥ 2.6) and insulin-sensitive (HOMA-IR < 2.6). Liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were categorized as normal vs. elevated (AST of < 36.0 µkat/L or ≥ 36.0 µkat/L; ALT of < 30.0 µkat/L or ≥ 30.0 µkat/L; ALT > 26 µkat/L males, > 22 µkat/L females). We examined differences in baseline cardiometabolic risk factors by WHtR tertiles and sex-specific multivariable logistic regression models to predict HOMA-IR and elevation of liver enzymes. Results Study participants had a mean WHtR of 0.59 ([SD: 0.06]). Irrespective of sex, children in WHtR T3 had higher BMIz scores, blood pressure, triglycerides, 2-h glucose, fasting 2-h insulin, and lower high-density lipoprotein cholesterol (HDL-C) concentrations than those in T2 and T1. After adjusting for covariates, the odds of elevated HOMA-IR (> 2.6) were over five-fold higher among males in T3 versus T1 [OR, 95%CI: 5.83, 2.34–14.52] and T2 [OR, 95%CI: 4.81, 1.94–11.92] and females in T3 [OR, 95%CI: 5.06, 2.10–12.20] versus T1. The odds of elevated ALT values (≥ 30) were 2.9 [95%CI: 1.01–8.41] fold higher among females in T3 compared to T1. Conclusion In public health settings, WHtR may be a practical screening tool in pediatric populations to identify children at risk of metabolic syndrome. Supplementary Information The online version contains supplementary material available at 10.1186/s12889-023-16418-9.

Dataset Information

Genetic Association of Waist-to-Hip Ratio With Cardiometabolic Traits, Type 2 Diabetes, and Coronary Heart Disease.

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Genetic Association of Waist-to-Hip Ratio With Cardiometabolic Traits, Type 2 Diabetes, and Coronary Heart Disease.

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