scholarly journals Assessing the causal impact of adiposity variation on rates of hospital admission: Application of Mendelian randomization

2020 ◽  
Author(s):  
Audinga-Dea Hazewinkel ◽  
Padraig Dixon ◽  
Rebecca Richmond ◽  
Kaitlin H Wade
Keyword(s):  
Body Mass Index ◽  
Hospital Admission ◽  
Body Mass ◽  
Hospital Admissions ◽  
Mendelian Randomization ◽  
Causal Role ◽  
Hospital Admission Rate ◽  
Admission Rates ◽  
Waist Hip Ratio

Background Body mass index (BMI) and waist-hip-ratio (WHR) are measures of adiposity, the former being a good marker for overall total body fat, the latter describing regional adiposity. Higher adiposity has been associated with the increased prevalence of many chronic diseases and a positive association between BMI and increased hospital admissions has previously been established. The aim of this study was to estimate the causal relationship between BMI, WHR and WHR adjusted for BMI (WHRadjBMI) and yearly hospital admission rates. Methods and Findings Mendelian randomization (MR) approaches were used to test the causal effect of BMI, WHR and WHRadjBMI on yearly hospital admission rates. Using data on 310,471 participants of White-British ancestry from the UK Biobank, we performed one-sample and two-sample MR analyses on the exposures individually and in a multivariable setting. MR analyses supported a causal role of adiposity on hospital admissions, with consistency across one- and two-sample MR methods. Primarily, one-sample MR analyses estimated fold-increases in yearly hospital admission rates of 1.13 (95% CI: 1.02, 1.27), 1.26 (95% CI: 1.00, 1.58) and 1.22 (95% CI: 1.01, 1.47) per SD for BMI, WHR and WHRadjBMI, respectively. A multivariable approach yielded estimates of 1.04 (95% CI: 0.99, 1.03) for BMI and 1.31 (95% CI: 1.04, 1.67) for WHR, while adjusting for WHR and BMI, respectively. Conclusions The results support a causal role of higher BMI and WHR in increasing the yearly hospital admission rate. The attenuation of the BMI effect, when adjusting for WHR in the multivariable MR analyses, suggested that an adverse fat distribution, rather than a higher BMI itself, may drive the relationship between adiposity and increased risk of hospital admission. Keywords: Body mass index (BMI), waist-hip-ratio (WHR), hospital admission, Mendelian randomization

scholarly journals Body mass index and mortality in UK Biobank: revised estimates using Mendelian randomization

2018 ◽  
Author(s):  
Kaitlin H Wade ◽  
David Carslake ◽  
Naveed Sattar ◽  
George Davey Smith ◽  
Nicholas J Timpson
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Genotypic Variation ◽  
Lung Cancer Mortality ◽  
Causal Role ◽  
Uk Biobank ◽  
All Cause Mortality

AbstractObjectiveObtain estimates of the causal relationship between different levels of body mass index (BMI) and mortality.MethodsMendelian randomization (MR) was conducted using genotypic variation reliably associated with BMI to test the causal effect of increasing BMI on all-cause and cause-specific mortality in participants of White British ancestry in UK Biobank.ResultsMR analyses supported existing evidence for a causal association between higher levels of BMI and greater risk of all-cause mortality (hazard ratio (HR) per 1kg/m2: 1.02; 95% CI: 0.97,1.06) and mortality from cardiovascular diseases (HR: 1.12; 95% CI: 1.02, 1.23), specifically coronary heart disease (HR: 1.19; 95% CI: 1.05, 1.35) and those other than stroke/aortic aneurysm (HR: 1.13; 95% CI: 0.93, 1.38), stomach cancer (HR: 1.30; 95% CI: 0.91, 1.86) and oesophageal cancer (HR: 1.08; 95% CI: 0.84, 1.38), and with decreased risk of lung cancer mortality (HR: 0.97; 95% CI: 0.84, 1.11). Sex-stratified analyses supported a causal role of higher BMI in increasing the risk of mortality from bladder cancer in males and other causes in females, but in decreasing the risk of respiratory disease mortality in males. The characteristic J-shaped observational association between BMI and mortality was visible with MR analyses but with a smaller value of BMI at which mortality risk was lowest and apparently flatter over a larger range of BMI.ConclusionResults support a causal role of higher BMI in increasing the risk of all-cause mortality and mortality from other causes. However, studies with greater numbers of deaths are needed to confirm the current findings.

scholarly journals Assessing the causal role of body mass index on cardiovascular health in young adults: Mendelian randomization and recall-by-genotype analyses

2017 ◽  
Author(s):  
Kaitlin H. Wade ◽  
Scott T. Chiesa ◽  
Alun D. Hughes ◽  
Nish Chaturvedi ◽  
Marietta Charakida ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Young Adults ◽  
Body Mass ◽  
Cardiovascular Health ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Left Ventricular ◽  
Causal Role ◽  
A Genome

ABSTRACTBackgroundMendelian randomization (MR) studies of body mass index (BMI) and cardiovascular health in mid-to-late life suggest causal relationships, but the nature of these has not been explored systematically at younger ages. Using complementary MR and recall-by-genotype (RbG) methodologies, our objective was to estimate the causal effect of BMI on detailed measures of cardiovascular health in a population of young healthy adults.Methods and FindingsData from the Avon Longitudinal Study of Parents and Children were used. For MR analyses, a genetic risk score (GRS) comprising 97 independent single nucleotide polymorphisms (SNPs) and constructed using external weighting was used as an instrument to test the causal effect of each unit increase in BMI (kg/m2) on selected cardiovascular phenotypes measured at age 17 (N=7909). An independent enriched sample from the same cohort participated in a RbG study at age 21, which enabled more detailed cardiovascular phenotyping (N=418; 191/227 from the lower/upper ∼30% of a genome-wide GRS distribution predicting variation in BMI). The causal effect of BMI on the additional cardiovascular phenotypes was assessed by comparing the two recalled groups. Difference in mean BMI between RbG groups was 3.85kg/m2 (95% CI: 2.53, 4.63; P=6.09×1011). In both MR and RbG analyses, results indicated that higher BMI causes higher blood pressure (BP) and left ventricular mass (indexed to height2.7, LVMI) in young adults (e.g. difference in LVMI per kg/m2 using MR: 1.07g/m2.7; 95% CI: 0.62, 1.52; P=3.87×10−06 and per 3.58kg/m2 using RbG: 1.65g/m2.7 95% CI: 0.83, 2.47; P=0.0001). Additionally, RbG results indicated a causal role of higher BMI on higher stroke volume (SV; difference per 3.58kg/m2: 1.49ml/m2.04; 95% CI: 0.62, 2.35; P=0.001) and cardiac output (CO; difference per 3.58kg/m2: 0.11l /min/m1.83; 95% CI: 0.03, 0.19; P=0.01). Neither analysis supported a causal role of higher BMI on heart rate.ConclusionsComplementary MR and RbG causal methodologies, together with a range of appropriate sensitivity analyses, showed that higher BMI is likely to cause worse cardiovascular health, specifically higher BP and LVMI, even in youth. These consistent results support efforts to prevent or reverse obesity in the young.

Body mass index in middle life and future risk of hospital admission for psychoses or depression: findings from the Renfrew/Paisley study

2007 ◽  
Vol 37 (8) ◽  
pp. 1151-1161 ◽  
Author(s):  
DEBBIE A. LAWLOR ◽  
CAROLE L. HART ◽  
DAVID J. HOLE ◽  
DAVID GUNNELL ◽  
GEORGE DAVEY SMITH
Keyword(s):  
Body Mass Index ◽  
Hospital Admission ◽  
Body Mass ◽  
Hospital Admissions ◽  
Long Term Follow Up ◽  
Psychiatric Outcomes ◽  
Future Hospital ◽  
Reduced Risk

ABSTRACTBackgroundThere is evidence that greater body mass index (BMI) protects against depression, schizophrenia and suicide. However, there is a need for prospective studies.MethodWe examined the association of BMI with future hospital admissions for psychoses or depression/anxiety disorders in a large prospective study of 7036 men and 8327 women. Weight and height were measured at baseline (1972–76) when participants were aged 45–64. Follow-up was for a median of 29 years.ResultsGreater BMI and obesity were associated with a reduced risk of hospital admission for psychoses and depression/anxiety in both genders, with the magnitude of these associations being the same for males and females. With adjustment for age, sex, smoking and social class, a 1 standard deviation (s.d.) greater BMI at baseline was associated with a rate ratio of 0·91 [95% confidence interval (CI) 0·82–1·01] for psychoses and 0·87 (95% CI 0·77–0·98) for depression/anxiety. Further adjustment for baseline psychological distress and total cholesterol did not alter these associations.ConclusionsOur findings add to the growing body of evidence that suggests that greater BMI is associated with a reduced risk of major psychiatric outcomes. Long-term follow-up of participants in randomized controlled trials of interventions that effectively result in weight loss and the use of genetic variants that are functionally related to obesity as instrumental variables could help to elucidate whether these associations are causal.

What Role Does Body Mass Index Play in Hospital Admission Rates From the Pediatric Emergency Department?

2013 ◽  
Vol 29 (9) ◽  
pp. 974-978 ◽  
Author(s):  
Sara Wyrick ◽  
Casey Hester ◽  
Amy Sparkman ◽  
Kathleen M. O’Neill ◽  
Greg Dupuis ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Emergency Department ◽  
Hospital Admission ◽  
Body Mass ◽  
Pediatric Emergency ◽  
Pediatric Emergency Department ◽  
Admission Rates

scholarly journals A phenome-wide multi-directional Mendelian randomization analysis of atrial fibrillation

2020 ◽  
Author(s):  
Qin Wang ◽  
Tom G Richardson ◽  
Eleanor Sanderson ◽  
Mika Ala-Korpela ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Body Mass Index ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Causal Role ◽  
Coronary Artery Diseases ◽  
Genetic Liability

AbstractBackgroundThe prevalence of atrial fibrillation (AF) is increasing with an aging worldwide population, yet a comprehensive understanding of its causes and consequences remains limited.ObjectivesTo assess the causes and consequences of AF via a multi-directional Mendelian randomization (MR) analysis scanning thousands of traits in a hypothesis-free approach.MethodsWe used publicly available GWAS data centralised and harmonised by the IEU open GWAS database. We assessed the potential causal role of 5048 exposures on risk of AF and the causal role of genetic liability to AF on 10,308 outcomes via two-sample MR analysis. Multivariable MR analysis was further conducted to explore the comparative role of identified risk factors.ResultsMR analysis suggested that 55 out of 5048 exposure traits, including four proteins, play a causal role in AF (P < 1e-5 allowing for multiple comparisons). Multivariable analysis suggested that higher body mass index, height, systolic blood pressure as well as genetic liability to coronary artery diseases independently cause AF. Three out of the four proteins (DUSP13, TNFSF12 and IL6R) had a drug prioritising score for atrial fibrillation of 0.26, 0.38 and 0.88, respectively (values closer to 1 indicating stronger evidence of the protein as a potential drug target). Genetic liability to AF was linked to a higher risk of cardioembolic ischemic stroke.ConclusionsBody mass index, height, systolic blood pressure and genetic liability to coronary artery diseases are independent causal risk factors for AF. Several proteins including DUSP13, IL-6R and TNFSF12 may represent therapeutic potential for preventing AF.

The relationship between body mass index and the risk of development of Dupuytren’s disease: a Mendelian randomization study

2020 ◽  
pp. 175319342095855
Author(s):  
Mustafa Majeed ◽  
Akira Wiberg ◽  
Michael Ng ◽  
Michael V. Holmes ◽  
Dominic Furniss
Keyword(s):  
Body Mass Index ◽  
Standard Deviation ◽  
Confidence Interval ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Dupuytren’S Disease ◽  
Standard Deviation Increase ◽  
Dupuytren's Disease ◽  
Relative Odds ◽  
Waist Hip Ratio

We performed Mendelian randomization analyses of body mass index and waist–hip ratio adjusted for body mass index in Dupuytren’s disease using summary statistics from genome-wide association study meta-analyses. We found that adiposity is causally protective against Dupuytren’s disease, with the inverse-variance weighted Mendelian randomization analysis estimating that a 1 standard deviation increase in body mass index (equivalent to 4.8 kg/m2) leads to 28% (95% confidence interval: 18–37%) lower relative odds of developing Dupuytren’s disease, and a 1 standard deviation increase in waist–hip ratio adjusted for body mass index (equivalent to a waist–hip ratio of 0.09) leads to 26% (95% confidence interval: 6–42%) lower relative odds of developing Dupuytren’s disease. We conclude from this study that regardless of the well-established negative health effects of obesity, the raised body mass index is associated with a lower risk of Dupuytren’s disease and may be causally protective for the development of the disease.

scholarly journals Changing patterns of hospital admission for asthma, 1981–97

Thorax ◽  
2001 ◽  
Vol 56 (9) ◽  
pp. 687-690
Author(s):  
D S Morrison ◽  
P McLoone
Keyword(s):  
Hospital Admission ◽  
Hospital Admissions ◽  
Admission Rate ◽  
Hospital Admission Rate ◽  
Admission Rates ◽  
Lengths Of Stay ◽  
Icd 10 ◽  
Changing Patterns ◽  
Bed Days ◽  
Age And Sex

BACKGROUNDHospital admission rates for asthma have stopped rising in several countries. The aim of this study was to use linked hospital admission data to explore recent trends in asthma admissions in Scotland.METHODSLinked Scottish Morbidity Records (SMR1) for asthma (ICD-9 493 and ICD-10 J45–6) from 1981 to 1997 were used to describe rates of first admissions and readmissions by age and sex. As a measure of resource use, annual trends in bed days used were also explored by age and sex.RESULTSThere were 160 039 hospital admissions for asthma by 82 421 individuals in Scotland during the study period. The overall hospital admission rate increased by 122% (from 106.7 to 236.7 per 100 000 population) but this varied by sex, age, and admission type. First admissions rose by 70% from 73.2 per 100 000 in 1986 to 124.8 per 100 000 in 1997 while readmissions fell. Children (<15 years) experienced a decline in overall admissions after 1992 due to falls in both new admissions and readmissions. By 1997 the ratio of female to male admissions was 0.57 in children, but 1.50 above 14 years of age. Mean lengths of stay fell from 10.7 days to 3.7 days between 1981 and 1997 and bed days used showed little change except for a decline after 1992 in children.CONCLUSIONSAfter a period of increasing hospitalisation for asthma in Scotland, rates of admission among children have begun to fall but among adults admissions continue to rise.

scholarly journals Causal role of high body mass index in multiple chronic diseases: a systematic review and meta-analysis of Mendelian randomization studies

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Susanna C. Larsson ◽  
Stephen Burgess
Keyword(s):  
Diabetes Mellitus ◽  
Body Mass Index ◽  
Chronic Diseases ◽  
Body Mass ◽  
Digestive System ◽  
Mendelian Randomization ◽  
De Novo ◽  
Meta Analysis ◽  
Mr Studies

Abstract Background Obesity is a worldwide epidemic that has been associated with a plurality of diseases in observational studies. The aim of this study was to summarize the evidence from Mendelian randomization (MR) studies of the association between body mass index (BMI) and chronic diseases. Methods PubMed and Embase were searched for MR studies on adult BMI in relation to major chronic diseases, including diabetes mellitus; diseases of the circulatory, respiratory, digestive, musculoskeletal, and nervous systems; and neoplasms. A meta-analysis was performed for each disease by using results from published MR studies and corresponding de novo analyses based on summary-level genetic data from the FinnGen consortium (n = 218,792 individuals). Results In a meta-analysis of results from published MR studies and de novo analyses of the FinnGen consortium, genetically predicted higher BMI was associated with increased risk of type 2 diabetes mellitus, 14 circulatory disease outcomes, asthma, chronic obstructive pulmonary disease, five digestive system diseases, three musculoskeletal system diseases, and multiple sclerosis as well as cancers of the digestive system (six cancer sites), uterus, kidney, and bladder. In contrast, genetically predicted higher adult BMI was associated with a decreased risk of Dupuytren’s disease, osteoporosis, and breast, prostate, and non-melanoma cancer, and not associated with Alzheimer’s disease, amyotrophic lateral sclerosis, or Parkinson’s disease. Conclusions The totality of the evidence from MR studies supports a causal role of excess adiposity in a plurality of chronic diseases. Hence, continued efforts to reduce the prevalence of overweight and obesity are a major public health goal.

Sign in / Sign up

Export Citation Format

Share Document