Effects Of Waist-to-hip Ratio Research Articles

Effects of general and central adiposity on circulating lipoprotein, lipid, and metabolite levels in UK Biobank: A multivariable Mendelian randomization study.

SummaryBackgroundThe direct effects of general adiposity (body mass index (BMI)) and central adiposity (waist-to-hip-ratio (WHR)) on circulating lipoproteins, lipids, and metabolites are unknown.MethodsWe used new metabolic data from UK Biobank (N=109,532, a five-fold higher N over previous studies). EDTA-plasma was used to quantify 249 traits with nuclear-magnetic-resonance spectroscopy including subclass-specific lipoprotein concentrations and lipid content, plus pre-glycemic and inflammatory metabolites. We used univariable and multivariable two-stage least-squares regression models with genetic risk scores for BMI and WHR as instruments to estimate total (unadjusted) and direct (mutually-adjusted) effects of BMI and WHR on metabolic traits; plus effects on statin use and interaction by sex, statin use, and age (proxy for medication use).FindingsHigher BMI decreased apolipoprotein B and low-density lipoprotein cholesterol (LDL-C) before and after WHR-adjustment, whilst BMI increased triglycerides only before WHR-adjustment. These effects of WHR were larger and BMI-independent. Direct effects differed markedly by sex, e.g., triglycerides increased only with BMI among men, and only with WHR among women. Adiposity measures increased statin use and showed metabolic effects which differed by statin use and age. Among the youngest (38-53y, statins-5%), BMI and WHR (per-SD) increased LDL-C (total effects: 0.04-SD, 95%CI=-0.01,0.08 and 0.10-SD, 95%CI=0.02,0.17 respectively), but only WHR directly. Among the oldest (63-73y, statins-29%), BMI and WHR directly lowered LDL-C (-0.19-SD, 95%CI=-0.27,-0.11 and -0.05-SD, 95%CI=-0.16,0.06 respectively).InterpretationExcess adiposity likely raises atherogenic lipid and metabolite levels exclusively via adiposity stored centrally, particularly among women. Apparent effects of adiposity on lowering LDL-C are likely explained by an effect of adiposity on statin use.FundingUK Medical Research Council; British Heart Foundation; Novo Nordisk; National Institute for Health Research; Wellcome Trust; Cancer Research UK

0034 Genetic Determinants of Cardiometabolic and Pulmonary Traits and Obstructive Sleep Apnea in the Hispanic Community Health Study/Study of Latinos

Abstract Introduction Obstructive sleep apnea (OSA) often co-occurs with other health outcomes. The respiratory event index (REI), often used to define OSA, is similarly correlated with several health phenotypes. Genetic data provide an opportunity to explain the nature of these associations. Methods We used data from the Hispanic Community Healthy Study/Study of Latinos (HCHS/SOL) to estimate genetic correlations (i.e., the correlation between phenotypes that is due to genetic effects) between OSA severity as measured by the REI and 56 anthropometric, glycemic, cardiometabolic, and pulmonary traits. Genetically-correlated traits (>0.2 and p-value<0.05) were carried forward for additional analysis. Using summary statistics from published genome-wide association studies (GWAS), we constructed Polygenic Risk Scores (PRSs) representing the genetic basis of each correlated trait and OSA, and studied their associations with the genetically-correlated traits, REI and OSA. OSA was defined as REI5. When a PRS for a correlated-trait was associated (p-value<0.05) with REI/OSA or vice versa, we used GWAS summary statistics to test causal relationships using Mendelian Randomization (MR) analysis. We further estimated correlated-trait PRS associations with REI and OSA in subgroups of individuals with and without obesity (BMI>30). Results The dataset included 11,155 participants (mean age: 46.2 (SD =13.8) years; 41.1% males) from the baseline HCHS/SOL exam who underwent home sleep apnea testing. 30.65% had OSA. 22 traits were genetically correlated with REI. Without BMI adjustment, the PRSs of BMI, waist-to-hip ratio (WHR), diastolic blood pressure (DBP), pulse pressure (PP), HbA1c, triglycerides (TG), FEV1/FVC and insomnia were significantly associated with REI/OSA. The associations of WHR, DBP, PP, HbA1c and insomnia PRSs and REI/OSA remained in BMI adjusted analysis. In obesity-stratified analysis, PRS of BMI, WHR and DBP were associated with REI/OSA in individuals with obesity, while PRSs of FEV1/FVC, HbA1c, insomnia, PP, TG, and WHR were associated with REI/OSA in individuals without obesity. MR analysis identified robust causal effect of increased BMI on OSA, and suggestive causal effects of WHR, DBP, and PP on OSA. Conclusion Our results support shared genetic basis of anthropometric traits, blood pressure traits, and insomnia with OSA, with potential differences in disease mechanisms in individuals with and without obesity. Support (If Any) Funding: R35HL135818, R21HL145425.

Abstract PD11-06: Associations between obesity and metastasis in the Carolina breast cancer study

Abstract Background. Metastatic disease accounts for the majority of breast cancer-specific mortality, and identifying women who are most at risk for metastasis remains an important challenge. Genomic risk scores are valuable tools in assessing risk of recurrence but have rarely been applied to assess risk of distant metastasis in large, diverse population-based cohorts. Such cohorts can identify important modifiers of the relationship between tumor genomics and metastasis. In particular, obesity at diagnosis has been implicated as a risk factor for breast cancer metastasis. Waist-to-hip ratio (WHR), as a measure of central adiposity, appears to increase risk of breast cancer mortality. It is important to understand how obesity impacts risk of metastasis and modifies other known prognostic factors. Methods. Data from the Carolina Breast Cancer Study, a prospective cohort of women with incident breast cancer that oversampled young women and black women such that each represented 50% of the study population, were used to study metastasis within five years of follow up (n=239 incident metastases in 2767 eligible participants with stage I-III disease). PAM50-derived risk-of-recurrence (ROR-PT) scores were measured using a research version of the 50-gene assay, and represent a multigene classifier incorporating tumor subtype, size, and proliferation score. Women with de novo metastasis (identified at diagnosis, n=109) were excluded, as incident and de novo metastases have different prognosis. Obesity was defined by WHR (> 0.85). Absolute risk within strata and risk differences between strata were calculated using the Kaplan-Meier estimator; models were adjusted with inverse probability weights conditional on grade, stage, age, and race, where appropriate. To examine the association between obesity and site or multiplicity of metastasis, relative frequency differences were estimated using generalized linear models. Results. The overall risk of metastasis in CBCS differed significantly by race (11.2% in Black women and 6.8% in non-Black women and was associated with higher ROR-PT score (19.8% in high ROR-PT vs. 6.5% in low or medium ROR-PT). 48.2% of women were classified as obese by WHR. Women with high WHR had a significantly higher absolute risk of metastasis (11.2%, 95% CI: 9.4, 13.0) relative to those with lower WHR (6.9, 95% CI: 5.6, 8.2). However, the effects of WHR on risk seemed to be isolated to those with high risk tumors. Non-obese and obese women with low-to-medium ROR-PT scores had similar risk of metastasis [RDLowMed (95% CI) = 1.5% (-1.5, 4.4)], while obese women with high ROR-PT scores had substantially higher risk of metastasis than non-obese women [RDHigh (95% CI) = 13.1% (4.3, 21.9); 26.2% vs. 13.1%]. Considering site of metastasis, more metastases were observed among women with high WHR at every site except brain. More occurrences of multiple metastases were also observed among obese women. Conclusions. Consistent with previous studies, we observed racial disparities in metastasis, with Black women having higher 5-year metastatic risk and with women with high ROR-PT scores also having higher risk. Obesity, herein measured by WHR, is an important predictor of metastatic risk and may modify the relationship between genomic risk scores and risk of metastasis. Citation Format: Linnea T Olsson, Andrea Walens, Alina M Hamilton, Halei C Benefield, Kevin P Williams, Jodie M Fleming, Stephen D Hursting, Melissa A Troester. Associations between obesity and metastasis in the Carolina breast cancer study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD11-06.

A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol.

Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ∼25% of the heritability of the phenotypes. To date, no unbiased screen for gene–environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79×10−9. There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.

Obesity Indices and Self‐Reported Functional Health in Men and Women in the EPIC‐Norfolk

To investigate the association between two indices of obesity, BMI and waist-to-hip ratio (WHR), and self-reported physical and mental functional health. We examined the relationship between obesity indices and self-reported physical and mental functional health measured by the Anglicized version of the Short-Form 36-item questionnaire in a population-based cross sectional study of 16,806 men and women 40 to 79 years old living in the general community in Norfolk, United Kingdom. Higher BMI and WHR were both independently associated with poorer self-reported physical functional health in men and women. The effect of BMI was greater in women compared with men, and the effect of WHR was greater in men compared with women, for poor physical functional health. Higher WHR but not BMI was associated with lower mental functional health in men and women. High BMI and WHR seem to be adversely related to self-perceived functional health in both men and women, although their relative impacts seem to differ by sex. Our findings also highlight the importance of using WHR in addition to BMI in assessing the impact of obesity on health outcome.

Abdominal obesity and risk of ischemic stroke: the Northern Manhattan Stroke Study.

Obesity is well recognized as a risk factor for coronary heart disease and mortality. The relationship between abdominal obesity and ischemic stroke remains less clear. Our aim was to evaluate abdominal obesity as an independent risk factor for ischemic stroke in a multiethnic community. A population-based, incident case-control study was conducted July 1993 through June 1997 in northern Manhattan, New York, NY. Cases (n=576) of first ischemic stroke (66% >or=BORDER="0">65 years of age; 56% women; 17% whites; 26% blacks; 55% Hispanics) were enrolled and matched by age, sex, and race-ethnicity to stroke-free community controls (n=1142). All subjects were interviewed and examined and had measurements of waist-to-hip ratio (WHR). Odds ratios (ORs) of ischemic stroke were calculated with gender-specific quartiles (GQs) and gender-specific medians of WHR adjusted for stroke risk factors and body mass index (BMI). Compared with the first quartile, the third and fourth quartiles of WHR had an increased risk of stroke (GQ3: OR, 2.4; 95% CI, 1.5 to 3.9; GQ4: OR, 3.0; 95% CI, 1.8 to 4.8) adjusted for other risk factors and BMI. Those with WHR equal to or greater than the median had an overall OR of 3.0 (95% CI, 2.1 to 4.2) for ischemic stroke even after adjustment for other risk factors and BMI. Increased WHR was associated with a greater risk of stroke in men and women and in all race-ethnic groups. The effect of WHR was stronger among younger persons (test for heterogeneity, P<0.0002) (<65 years of age: OR, 4.4; 95%CI, 2.2 to 9.0; >or=65 years of age: OR, 2.2; 95% CI, 1.4 to 3.2). WHR was associated with an increased risk among those with and without large-artery atherosclerotic stroke. Abdominal obesity is an independent, potent risk factor for ischemic stroke in all race-ethnic groups. It is a stronger risk factor than BMI and has a greater effect among younger persons. Prevention of obesity and weight reduction need greater emphasis in stroke prevention programs.