scholarly journals Body mass index and risk of dying from a bloodstream infection: A Mendelian randomization study

PLoS Medicine ◽  
2020 ◽  
Vol 17 (11) ◽  
pp. e1003413
Author(s):  
Tormod Rogne ◽  
Erik Solligård ◽  
Stephen Burgess ◽  
Ben M. Brumpton ◽  
Julie Paulsen ◽  
...  
Keyword(s):  
Body Mass Index ◽  
General Population ◽  
Bloodstream Infection ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Obesity Paradox ◽  
Hazard Ratio ◽  
European Ancestry ◽  
Health Study ◽  
Incidence And Mortality

Background In observational studies of the general population, higher body mass index (BMI) has been associated with increased incidence of and mortality from bloodstream infection (BSI) and sepsis. On the other hand, higher BMI has been observed to be apparently protective among patients with infection and sepsis. We aimed to evaluate the causal association of BMI with risk of and mortality from BSI. Methods and findings We used a population-based cohort in Norway followed from 1995 to 2017 (the Trøndelag Health Study [HUNT]), and carried out linear and nonlinear Mendelian randomization analyses. Among 55,908 participants, the mean age at enrollment was 48.3 years, 26,324 (47.1%) were men, and mean BMI was 26.3 kg/m2. During a median 21 years of follow-up, 2,547 (4.6%) participants experienced a BSI, and 451 (0.8%) died from BSI. Compared with a genetically predicted BMI of 25 kg/m2, a genetically predicted BMI of 30 kg/m2 was associated with a hazard ratio for BSI incidence of 1.78 (95% CI: 1.40 to 2.27; p < 0.001) and for BSI mortality of 2.56 (95% CI: 1.31 to 4.99; p = 0.006) in the general population, and a hazard ratio for BSI mortality of 2.34 (95% CI: 1.11 to 4.94; p = 0.025) in an inverse-probability-weighted analysis of patients with BSI. Limitations of this study include a risk of pleiotropic effects that may affect causal inference, and that only participants of European ancestry were considered. Conclusions Supportive of a causal relationship, genetically predicted BMI was positively associated with BSI incidence and mortality in this cohort. Our findings contradict the “obesity paradox,” where previous traditional epidemiological studies have found increased BMI to be apparently protective in terms of mortality for patients with BSI or sepsis.

Body mass index and risk of mental disorders in the general population: Results from the Singapore Mental Health Study

2013 ◽  
Vol 74 (2) ◽  
pp. 135-141 ◽  
Author(s):  
Mythily Subramaniam ◽  
Louisa Picco ◽  
Vincent He ◽  
Janhavi Ajit Vaingankar ◽  
Edimansyah Abdin ◽  
...  
Keyword(s):  
Mental Health ◽  
Body Mass Index ◽  
General Population ◽  
Mental Disorders ◽  
Body Mass ◽  
Health Study ◽  
Mental Health Study

Low-frequency coding variants associated with body-mass-index impact the success of bariatric surgery

2021 ◽  
Author(s):  
Darlène Antoine ◽  
Rosa-Maria Guéant-Rodriguez ◽  
Jean-Claude Chèvre ◽  
Sébastien Hergalant ◽  
Tanmay Sharma ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Body Mass Index ◽  
Morbid Obesity ◽  
General Population ◽  
Body Mass ◽  
Intervention Program ◽  
Low Frequency ◽  
European Ancestry ◽  
Frequency Coding ◽  
Coding Variants

Abstract Context A recent study identified 14 low-frequency coding variants associated with body-mass-index (BMI) in 718,734 individuals predominantly of European ancestry. Objective and design The 14 low-frequency coding variants were genotyped or sequenced in 342 French adults with severe/morbid obesity and 574 French adult controls from the general population. We built risk and protective genetic scores (GS) based on 6 BMI-increasing and 5 BMI-decreasing low-frequency coding variants that were polymorphic in our study. We investigated the association of the two GS with i) the risk of severe/morbid obesity, ii) BMI variation before weight-loss intervention, iii) BMI change in response to an 18-month lifestyle/behavioral intervention program, and iv) BMI change up to 24 months after bariatric surgery. Results While the risk GS was not associated with severe/morbid obesity status, BMI-decreasing low-frequency coding variants were significantly less frequent in patients with severe/morbid obesity than in French adults from the general population. Neither the risk nor the protective GS was associated with BMI before intervention in patients with severe/morbid obesity, nor did they impact BMI change in response to a lifestyle/behavioral modification program. The protective GS was associated with a greater BMI decrease following bariatric surgery. The risk and protective GS were associated with a higher and lower risk of BMI regain after bariatric surgery. Conclusion Our data indicate that in populations of European descent, low-frequency coding variants associated with BMI in the general population also impact the outcomes of bariatric surgery in patients with severe/morbid obesity.

scholarly journals Body mass index and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study

2021 ◽  
Author(s):  
Alvaro Hernaez ◽  
Tormod Rogne ◽  
Karoline H. Skara ◽  
Siri E. Haberg ◽  
Christian M. Page ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Cohort Study ◽  
Body Mass ◽  
Mendelian Randomization ◽  
European Ancestry ◽  
Current Evidence ◽  
Obese Women ◽  
Time To Pregnancy ◽  
Current Evidence Base ◽  
Multivariable Regression

Background. Higher body mass index (BMI) is associated with subfertility in women and men. This relationship is further substantiated by a few small randomized-controlled trials of weight reduction and success of assisted reproduction. The aim of the current study was to expand the current evidence-base by investigating the association between BMI and subfertility in men and women using multivariable regression and Mendelian randomization. Methods and findings. We studied 34,157 women (average age 30, average BMI 23.1 kg/m2) and 31,496 men (average age 33, average BMI 25.4 kg/m2) who were genotyped and are participating in the Norwegian Mother, Father and Child Cohort Study. Self-reported information was available on time-to-pregnancy and BMI. A total of 10% of couples were subfertile (time-to-pregnancy ≥12 months). Our findings support a J-shaped association between BMI and subfertility in both sexes using multivariable logistic regression models. Non-linear Mendelian randomization validated this relationship. A 1 kg/m2 greater genetically predicted BMI was linked to 15% greater odds of subfertility (95% confidence interval 4% to 28%) in obese women (>=30.0 kg/m2) and 14% lower odds of subfertility (-25% to -3%) in women with BMI <20.0 kg/m2. A 1 kg/m2 higher genetically predicted BMI was linked to 23% greater odds of subfertility (6% to 43%) among obese men and 36% decreased odds (-62% to 7%) among men BMI <20.0 kg/m2. A genetically predicted BMI of 23 and 25 kg/m2 was linked to the lowest subfertility risk in women and men, respectively. The main limitations of our study were that we did not know whether the subfertility was driven by the woman, man, or both; the exclusive consideration of individuals of northern European ancestry; and the limited amount of participants with obesity or BMI values <20.0 kg/m2. Conclusions. We observed a J-shaped relationship between BMI and subfertility in both sexes, when using both a standard multivariable regression and Mendelian randomization analysis, further supporting a potential causal role of BMI on subfertility.

Maternal Hypertension Increases Risk of Preeclampsia and Low Fetal Birthweight: Genetic Evidence From a Mendelian Randomization Study

Hypertension ◽  
2022 ◽  
Author(s):  
Maddalena Ardissino ◽  
Eric A.W. Slob ◽  
Ophelia Millar ◽  
Rohin K. Reddy ◽  
Laura Lazzari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Body Mass ◽  
Mendelian Randomization ◽  
European Ancestry ◽  
Increased Risk

Background: Maternal cardiovascular risk factors have been associated with adverse maternal and fetal outcomes. Given the difficulty in establishing causal relationships using epidemiological data, we applied Mendelian randomization to explore the role of cardiovascular risk factors on risk of developing preeclampsia or eclampsia, and low fetal birthweight. Methods: Uncorrelated single-nucleotide polymorphisms associated systolic blood pressure (SBP), body mass index, type 2 diabetes, LDL (low-density lipoprotein) with cholesterol, smoking, urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate at genome-wide significance in studies of 298 957 to 1 201 909 European ancestry participants were selected as instrumental variables. A 2-sample Mendelian randomization study was performed with primary outcome of preeclampsia or eclampsia (PET). Risk factors associated with PET were further investigated for their association with low birthweight. Results: Higher genetically predicted SBP was associated increased risk of PET (odds ratio [OR] per 1-SD SBP increase 1.90 [95% CI=1.45–2.49]; P =3.23×10 −6 ) and reduced birthweight (OR=0.83 [95% CI=0.79–0.86]; P =3.96×10 −18 ), and this was not mediated by PET. Body mass index and type 2 diabetes were also associated with PET (respectively, OR per 1-SD body mass index increase =1.67 [95% CI=1.44–1.94]; P =7.45×10 −12 ; and OR per logOR increase type 2 diabetes =1.11 [95% CI=1.04–1.19]; P =1.19×10 −3 ), but not with reduced birthweight. Conclusions: Our results provide evidence for causal effects of SBP, body mass index, and type 2 diabetes on PET and identify that SBP is associated with reduced birthweight independently of PET. The results provide insight into the pathophysiological basis of PET and identify hypertension as a potentially modifiable risk factor amenable to therapeutic intervention.

scholarly journals Risk factors mediating the effect of body mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis

2021 ◽  
Author(s):  
Dipender Gill ◽  
Verena Zuber ◽  
Jesse Dawson ◽  
Jonathan Pearson-Stuttard ◽  
Alice R. Carter ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
European Ancestry ◽  
Standard Deviation Increase ◽  
Waist To Hip Ratio ◽  
Artery Disease

Abstract Background Higher body mass index (BMI) and waist-to-hip ratio (WHR) increase the risk of cardiovascular disease, but the extent to which this is mediated by blood pressure, diabetes, lipid traits, and smoking is not fully understood. Methods Using consortia and UK Biobank genetic association summary data from 140,595 to 898,130 participants predominantly of European ancestry, Mendelian randomization mediation analysis was performed to investigate the degree to which systolic blood pressure (SBP), diabetes, lipid traits, and smoking mediated an effect of BMI and WHR on the risk of coronary artery disease (CAD), peripheral artery disease (PAD) and stroke. Results The odds ratio of CAD per 1-standard deviation increase in genetically predicted BMI was 1.49 (95% CI 1.39 to 1.60). This attenuated to 1.34 (95% CI 1.24 to 1.45) after adjusting for genetically predicted SBP (proportion mediated 27%, 95% CI 3% to 50%), to 1.27 (95% CI 1.17 to 1.37) after adjusting for genetically predicted diabetes (41% mediated, 95% CI 18% to 63%), to 1.47 (95% CI 1.36 to 1.59) after adjusting for genetically predicted lipids (3% mediated, 95% −23% to 29%), and to 1.46 (95% CI 1.34 to 1.58) after adjusting for genetically predicted smoking (6% mediated, 95% CI −20% to 32%). Adjusting for all the mediators together, the estimate attenuated to 1.14 (95% CI 1.04 to 1.26; 66% mediated, 95% CI 42% to 91%). A similar pattern was observed when considering genetically predicted WHR as the exposure, and PAD or stroke as the outcome. Conclusions Measures to reduce obesity will lower the risk of cardiovascular disease primarily by impacting downstream metabolic risk factors, particularly diabetes and hypertension. Reduction of obesity prevalence alongside control and management of its mediators is likely to be most effective for minimizing the burden of obesity.

scholarly journals Estimate of prevalent ischemic stroke from triglyceride glucose-body mass index in the general population

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhi Du ◽  
Liying Xing ◽  
Min Lin ◽  
Yingxian Sun
Keyword(s):  
Body Mass Index ◽  
Ischemic Stroke ◽  
General Population ◽  
Body Mass ◽  
Density Lipoprotein ◽  
Cubic Spline ◽  
Lipoprotein Cholesterol ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
The Relationship

Abstract Background To investigate the relationship between triglyceride glucose-body mass index (TyG-BMI) and ischemic stroke. Methods Leveraging two Chinese general population surveys, the Northeast China Rural Cardiovascular Health Study (NCRCHS, N = 11,097) and the National Stroke Screening and Intervention Program in Liaoning (NSSIPL, N = 10,862), we evaluated the relationship between TyG-BMI and ischemic stroke by a restricted cubic spline and multivariate logistic regression after adjusting age, sex, level of education, exercise regularly, current smoking, current drinking, atrial fibrillation, hypertension, coronary artery disease, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The category-free analysis was used to determine whether TyG-BMI enhanced the capacity of estimating ischemic stroke. Results A total of 596 and 347 subjects, respectively, from NSSIPL and NCRCHS were survivors of ischemic stroke. In NSSIPL, the relationship between TyG-BMI and ischemic stroke was linear and did not have a threshold or saturation effect according to the results of the restricted cubic spline. The regression analysis indicated that the risk of ischemic stroke increased 20% for per SD increase of TyG-BMI after multivariate adjustment [odds ratio (OR): 1.20, 95% confidence interval (CI): 1.10–1.32]. Compared with those in the lowest tertile, the risk of ischemic stroke in subjects with intermediate and high TyG-BMI was significantly higher [OR (95% CI): 1.39 (1.10–1.74); OR (95% CI) 1.72 (1.37–2.17), respectively]. Category-free analysis indicated that TyG-BMI had a remarkable improvement in the ability to estimate prevalent ischemic stroke [NRI (95% CI): 0.188 (0.105–0.270)]. These abovementioned relationships were confirmed in NCRCHS. Conclusions The present study found the robust correlation between TyG-BMI and ischemic stroke, independently of a host of conventional risk factors. Meanwhile, our findings also suggested the potential usefulness of TyG-BMI to improve the risk stratification of ischemic stroke.

scholarly journals Elucidation of causal direction between asthma and obesity: a bi-directional Mendelian randomization study

2019 ◽  
Vol 48 (3) ◽  
pp. 899-907 ◽  
Author(s):  
Shujing Xu ◽  
Frank D Gilliland ◽  
David V Conti
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
European Ancestry ◽  
Summary Statistics ◽  
Adult Body Mass ◽  
Causal Direction ◽  
Genome Wide ◽  
Adult Body

Abstract Background Observational associations between asthma and obesity are well established, but inferring causality is challenging. We leveraged publicly available summary statistics to ascertain the causal direction between asthma and obesity via Mendelian randomization in European-ancestry adults. Methods We performed two-sample bi-directional Mendelian randomization analysis using publicly available genome-wide association studies summary statistics. Single nucleotide polymorphisms associated with asthma and body mass index at genome-wide significance were combined using a fixed effect meta-analysis in each direction. An extensive sensitivity analysis was considered. Results There was evidence in support of increasing causal effect of body mass index on risk of asthma (odds ratio 1.18 per unit increase, 95% confidence interval (CI) (1.11, 1.25), P = 2 × 10−8. No significant causal effect of asthma on adult body mass index was observed [estimate −0.004, 95% CI (−0.018, 0.009), P = 0.553]. Conclusions Our results confirmed that in European-ancestry populations, adult body mass index is likely to be causally linked to the risk of asthma; yet the effect of asthma on body mass index is small, if present at all.

scholarly journals Body composition and mortality in the general population: A review of epidemiologic studies

2018 ◽  
Vol 243 (17-18) ◽  
pp. 1275-1285 ◽  
Author(s):  
Dong Hoon Lee ◽  
Edward L Giovannucci
Keyword(s):  
Body Mass Index ◽  
Body Composition ◽  
General Population ◽  
Lean Body Mass ◽  
Body Mass ◽  
Fat Mass ◽  
Obesity Paradox ◽  
Epidemiologic Studies ◽  
Risk Of Mortality ◽  
Increased Risk

Numerous studies have examined the association between body mass index and mortality and often observed that risk of mortality was higher in those with lower body mass index than those who were overweight or even obese (“obesity paradox”). One potential explanation of the obesity paradox is the limitation of body mass index as an imperfect measure of adiposity. However, relatively few studies have examined the association between body composition and mortality due to practical issues of assessing body composition in large-scale epidemiological settings. The available epidemiologic studies on this topic were heterogenous with regard to study design, analyses, results, and interpretations. The majority of studies using direct body composition measures such as dual-energy x-ray absorptiometry or computed tomography had relatively small sample size, short follow-up period and restricted study population. Studies have also used other approaches to indirectly estimate body composition to examine the association with mortality in a larger and more representative population. Overall findings were not consistent but suggested that fat mass and lean body mass may play an independent role on mortality in the general population. Various shapes of the associations were observed, but studies generally suggested that high fat mass was associated with increased risk of mortality (especially higher range of fat mass) and low lean body mass was associated with increased risk of mortality (especially lower range of lean body mass). On the other hand, fat mass and lean body mass tended to show either null or inverse association with mortality in elderly populations. Given the complex relationship of two body components as well as with other factors (e.g., age, smoking, disease, etc.), future studies should be conducted and interpreted after careful consideration of potential biases. In summary, the available data suggest independent associations of fat mass and lean body mass on mortality in the general population. Impact statement Current understanding of the association of body composition on mortality in the general population is limited. This review evaluated the available epidemiologic studies on body composition and mortality that leveraged diverse approaches to estimate body composition. Although studies showed inconsistent results, there was evidence suggesting that high fat mass and low lean body mass may be independently associated with mortality in the general population. This review may help partially explain the “obesity paradox” phenomenon and facilitate further studies to advance the understanding of the association of body composition on health in the general and patient populations.

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