Association of Body Mass Index With Cardiometabolic Disease in the UK Biobank

Lyall, Donald M.; Celis‐Morales, Carlos; Ward, Joey; Iliodromiti, Stamatina; Anderson, Jana; Gill, Jason M.R.; Smith, Daniel J.; Ntuk, U. E.; Mackay, Daniel; Holmes, Michael V.; Sattar, Naveed; Pell, Jill P.

doi:10.1001/jamacardio.2016.5804

Cited by 207 publications

(191 citation statements)

References 33 publications

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“…Obesity traits were causally related to higher risk of T2D, in keeping with previous studies (6)(7)(8)(9)(10)(11)19,64). We could not detect a sex difference in risk of T2D from higher WHR or WHRadjBMI.…”

Section: Diabetessupporting

confidence: 89%

“…All obesity traits increased risk of CAD in both sexes, with no difference detected in the magnitude of effect between women and men. The associations with risk of CAD in men and women combined are consistent with previous studies (4,(6)(7)(8)10,11,15,17). While observational studies have indicated that waist-related traits may be more strongly associated with cardiovascular disease in women than men, they have not been conclusive (15,17,76).…”

Section: Cardiovascular Diseasesupporting

confidence: 84%

“…Previous studies have found causal relationships between higher BMI and WHR adjusted for BMI (WHRadjBMI) and type 2 diabetes (T2D) and coronary artery disease (CAD), using a limited number of previously known obesity-associated SNPs (6)(7)(8)(9)(10)(11). However, sex-specific relationships are largely unexplored as is the the role that obesity traits play in the leading causes of death beyond these cardiometabolic diseases.…”

Section: Introductionmentioning

confidence: 99%

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Causal relevance of obesity on the leading causes of death in women and men: A Mendelian randomization study

Censin

Bovijn

Ferreira³

et al. 2019

Preprint

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Obesity traits are causally implicated with risk of cardiometabolic diseases. It remains unclear whether there are similar causal effects of obesity traits on other non-communicable diseases. Also, it is largely unexplored whether there are any sex-specific differences in the causal effects of obesity traits on cardiometabolic diseases and other leading causes of death.We constructed sex-specific genetic risk scores (GRS) for three obesity traits; body mass index (BMI), waist-hip ratio (WHR), and WHR adjusted for BMI, including 565, 324, and 337 genetic variants, respectively. These GRSs were then used as instrumental variables to assess associations between the obesity traits and leading causes of mortality in the UK Biobank using Mendelian randomization. We also investigated associations with potential mediators, including smoking, glycemic and blood pressure traits. Sex-differences were subsequently assessed by Cochran's Q-test (Phet).A Mendelian randomization analysis of 228,466 women and 195,041 men showed that obesity causes coronary artery disease, stroke (particularly ischemic), chronic obstructive pulmonary disease, lung cancer, type 2 and 1 diabetes mellitus, non-alcoholic fatty liver disease, chronic liver disease, and acute and chronic renal failure. Higher BMI led to higher risk of type 2 diabetes in women than in men (Phet=1.4×10 -5 ). Waist-hip-ratio led to a higher risk of chronic obstructive pulmonary disease (Phet=3.7×10 -6 ) and higher risk of chronic renal failure (Phet=1.0×10 -4 ) in men than women.Obesity traits have an etiological role in the majority of the leading global causes of death. Sex differences exist in the effects of obesity traits on risk of type 2 diabetes, chronic obstructive pulmonary disease, and renal failure, which may have downstream implications for public health. 4 Author summaryObesity is increasing globally and has been linked to major causes of death, such as diabetes and heart disease. Still, the causal effects of obesity on other leading causes of death is relatively unexplored. It is also unclear if any such effects differ between men and women.Mendelian randomization is a method that explores causal relationships between traits using genetic data. Using Mendelian randomization, we investigated the effects of obesity traits on leading causes of death and assessed if any such effects differ between men and women.

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Section: Diabetessupporting

confidence: 89%

Section: Cardiovascular Diseasesupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Causal relevance of obesity on the leading causes of death in women and men: A Mendelian randomization study

Censin

Bovijn

Ferreira³

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…32 People with obesity, as compared to those of a healthy weight are at increased risk for many serious diseases and health conditions affecting multiple organ systems. 33–35 “Recent data provides strong evidence for a causal role of higher BMI and risk of type 2 diabetes and hypertension, and evidence that BMI increases risk of coronary heart disease.” 36 Obesity is associated with an increase in CVD such as coronary artery disease and stroke as well as CVD risk factors such as hypertension and dyslipidemia. Obesity is also associated with prediabetes (when the blood glucose level is higher than normal) and type 2 diabetes.…”

Section: Impactmentioning

confidence: 99%

Obesity in the Workplace

Yarborough

Brethauer

Burton

et al. 2018

Journal of Occupational &Amp; Environmental Medicine

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Objective To conduct a comprehensive literature review to develop recommendations for managing obesity among workers to improve health outcomes and to explore the impact of obesity on health costs to determine if a case can be made for surgical interventions and insurance coverage. Methods We searched PubMed from 2011–2016, and CINAHL, Scopus, and Cochrane Registry of Clinical Trials for interventions addressing obesity in the workplace. Results A total of 1,419 articles were screened, resulting in 275 articles being included. Several areas were identified that require more research and investigation. Conclusions Our findings support the use of both lifestyle modification and bariatric surgery to assist appropriate patients in losing weight.

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“…The underlying biological relationship between adiposity and health is complex (4), but the endocrinal (5), cardiometabolic (6,7) and other changes (8) associated with increased adiposity are themselves linked to substantial healthcare resource requirements (9). Increases in the mean and variance of adiposity, reflected in widely used measures of nutritional status such as body mass index (BMI -weight divided by the square of standing height) have led to important changes in the global distribution of adiposity (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

The causal effect of adiposity on hospital costs: Mendelian Randomization analysis of over 300,000 individuals from the UK Biobank

Dixon¹,

Hollingworth²,

Harrison³

et al. 2019

Preprint

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Estimates of the marginal effect of measures of adiposity such as body mass index (BMI) on healthcare costs are important for the formulation and evaluation of policies targeting adverse weight profiles. Many existing estimates of this association are affected by endogeneity bias caused by simultaneity, measurement error and omitted variables. The contribution of this study is to avoid this bias by using a novel identification strategy -random germline genetic variation in an instrumental variable analysis -to identify the presence and magnitude of the causal effect of BMI on inpatient hospital costs. We also use data on genetic variants to undertake much richer testing of the sensitivity of results to potential violations of the instrumental variable assumptions than is possible with existing approaches. Using data on over 300,000 individuals, we found effect sizes for the marginal unit of BMI more than 50% larger than multivariable effect sizes. These effects attenuated under sensitivity analyses, but remained larger than multivariable estimates for all but one estimator. There was little evidence for non-linear effects of BMI on hospital costs. Within-family estimates, intended to address dynastic biases, were null but suffered from low power. This paper is the first to use genetic variants in a Mendelian Randomization framework to estimate the causal effect of BMI (or any other disease/trait) on healthcare costs. This type of analysis can be used to inform the cost-effectiveness of interventions and policies targeting the prevention and treatment of overweight and obesity, and for setting research priorities.

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Association of Body Mass Index With Cardiometabolic Disease in the UK Biobank

Abstract: The results of this study add to the burgeoning evidence of an association between higher BMI and increased risk of cardiometabolic diseases. This finding has relevance for public health policies in many countries with increasing obesity levels.

Cited by 207 publications

References 33 publications

Causal relevance of obesity on the leading causes of death in women and men: A Mendelian randomization study

Causal relevance of obesity on the leading causes of death in women and men: A Mendelian randomization study

Obesity in the Workplace

The causal effect of adiposity on hospital costs: Mendelian Randomization analysis of over 300,000 individuals from the UK Biobank

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