BMI and Mortality in UK Biobank: Revised Estimates Using Mendelian Randomization

Kaitlin Wade; David Carslake; Naveed Sattar; George Davey Smith; Nicholas Timpson

doi:10.1002/oby.22313

BMI and Mortality in UK Biobank: Revised Estimates Using Mendelian Randomization

Kaitlin Wade, David Carslake, Naveed Sattar, George Davey Smith, Nicholas Timpson

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Abstract

Objective

The aim of this study was to obtain estimates of the causal relationship between BMI and mortality.

Methods

Mendelian randomization (MR) with BMI‐associated genotypic variation was used to test the causal effect of BMI on all‐cause and cause‐specific mortality in UK Biobank participants of White British ancestry.

Results

MR analyses supported a causal association between higher BMI and greater risk of all‐cause mortality (hazard ratio [HR] per 1 kg/m2: 1.03; 95% CI: 0.99‐1.07) and mortality from cardiovascular diseases (HR: 1.10; 95% CI: 1.01‐1.19), specifically coronary heart disease (HR: 1.12; 95% CI: 1.00‐1.25) and those excluding coronary heart disease/stroke/aortic aneurysm (HR: 1.24; 95% CI: 1.03‐1.48), stomach cancer (HR: 1.18; 95% CI: 0.87‐1.62), and esophageal cancer (HR: 1.22; 95% CI: 0.98‐1.53), and a decreased risk of lung cancer mortality (HR: 0.96; 95% CI: 0.85‐1.08). Sex stratification supported the causal role of higher BMI increasing bladder cancer mortality risk (males) but decreasing respiratory disease mortality risk (males). The J‐shaped observational association between BMI and mortality was visible with MR analyses, but the BMI at which mortality was minimized was lower and the association was flatter over a larger BMI range.

Conclusions

Results support a causal role of higher BMI in increasing the risk of all‐cause mortality and mortality from several specific causes.

Original language	English
Pages (from-to)	1796-1806
Number of pages	11
Journal	Obesity
Volume	26
Issue number	11
Early online date	25 Oct 2018
DOIs	https://doi.org/10.1002/oby.22313
Publication status	Published - Nov 2018

Structured keywords

ICEP

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/oby.22313

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Persistent link

IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. & Davey Smith, G.
1/04/18 → 31/03/23
Project: Research

Professor Nicholas John Timpson
- N.J.Timpsonbristol.acuk
- Bristol Medical School (PHS) - Professor of Genetic Epidemiology
- Bristol Population Health Science Institute
- MRC Integrative Epidemiology Unit
- Cancer
Person: Academic , Member

Cite this

@article{1c55a809eb2941439e1e8ac3e54e49eb,

title = "BMI and Mortality in UK Biobank: Revised Estimates Using Mendelian Randomization",

abstract = "ObjectiveThe aim of this study was to obtain estimates of the causal relationship between BMI and mortality.MethodsMendelian randomization (MR) with BMI‐associated genotypic variation was used to test the causal effect of BMI on all‐cause and cause‐specific mortality in UK Biobank participants of White British ancestry.ResultsMR analyses supported a causal association between higher BMI and greater risk of all‐cause mortality (hazard ratio [HR] per 1 kg/m2: 1.03; 95% CI: 0.99‐1.07) and mortality from cardiovascular diseases (HR: 1.10; 95% CI: 1.01‐1.19), specifically coronary heart disease (HR: 1.12; 95% CI: 1.00‐1.25) and those excluding coronary heart disease/stroke/aortic aneurysm (HR: 1.24; 95% CI: 1.03‐1.48), stomach cancer (HR: 1.18; 95% CI: 0.87‐1.62), and esophageal cancer (HR: 1.22; 95% CI: 0.98‐1.53), and a decreased risk of lung cancer mortality (HR: 0.96; 95% CI: 0.85‐1.08). Sex stratification supported the causal role of higher BMI increasing bladder cancer mortality risk (males) but decreasing respiratory disease mortality risk (males). The J‐shaped observational association between BMI and mortality was visible with MR analyses, but the BMI at which mortality was minimized was lower and the association was flatter over a larger BMI range.ConclusionsResults support a causal role of higher BMI in increasing the risk of all‐cause mortality and mortality from several specific causes.",

author = "Kaitlin Wade and David Carslake and Naveed Sattar and {Davey Smith}, George and Nicholas Timpson",

year = "2018",

month = nov,

doi = "10.1002/oby.22313",

language = "English",

volume = "26",

pages = "1796--1806",

journal = "Obesity",

issn = "1930-7381",

publisher = "John Wiley & Sons, Inc",

number = "11",

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T1 - BMI and Mortality in UK Biobank

T2 - Revised Estimates Using Mendelian Randomization

AU - Wade, Kaitlin

AU - Carslake, David

AU - Sattar, Naveed

AU - Davey Smith, George

AU - Timpson, Nicholas

PY - 2018/11

Y1 - 2018/11

N2 - ObjectiveThe aim of this study was to obtain estimates of the causal relationship between BMI and mortality.MethodsMendelian randomization (MR) with BMI‐associated genotypic variation was used to test the causal effect of BMI on all‐cause and cause‐specific mortality in UK Biobank participants of White British ancestry.ResultsMR analyses supported a causal association between higher BMI and greater risk of all‐cause mortality (hazard ratio [HR] per 1 kg/m2: 1.03; 95% CI: 0.99‐1.07) and mortality from cardiovascular diseases (HR: 1.10; 95% CI: 1.01‐1.19), specifically coronary heart disease (HR: 1.12; 95% CI: 1.00‐1.25) and those excluding coronary heart disease/stroke/aortic aneurysm (HR: 1.24; 95% CI: 1.03‐1.48), stomach cancer (HR: 1.18; 95% CI: 0.87‐1.62), and esophageal cancer (HR: 1.22; 95% CI: 0.98‐1.53), and a decreased risk of lung cancer mortality (HR: 0.96; 95% CI: 0.85‐1.08). Sex stratification supported the causal role of higher BMI increasing bladder cancer mortality risk (males) but decreasing respiratory disease mortality risk (males). The J‐shaped observational association between BMI and mortality was visible with MR analyses, but the BMI at which mortality was minimized was lower and the association was flatter over a larger BMI range.ConclusionsResults support a causal role of higher BMI in increasing the risk of all‐cause mortality and mortality from several specific causes.

AB - ObjectiveThe aim of this study was to obtain estimates of the causal relationship between BMI and mortality.MethodsMendelian randomization (MR) with BMI‐associated genotypic variation was used to test the causal effect of BMI on all‐cause and cause‐specific mortality in UK Biobank participants of White British ancestry.ResultsMR analyses supported a causal association between higher BMI and greater risk of all‐cause mortality (hazard ratio [HR] per 1 kg/m2: 1.03; 95% CI: 0.99‐1.07) and mortality from cardiovascular diseases (HR: 1.10; 95% CI: 1.01‐1.19), specifically coronary heart disease (HR: 1.12; 95% CI: 1.00‐1.25) and those excluding coronary heart disease/stroke/aortic aneurysm (HR: 1.24; 95% CI: 1.03‐1.48), stomach cancer (HR: 1.18; 95% CI: 0.87‐1.62), and esophageal cancer (HR: 1.22; 95% CI: 0.98‐1.53), and a decreased risk of lung cancer mortality (HR: 0.96; 95% CI: 0.85‐1.08). Sex stratification supported the causal role of higher BMI increasing bladder cancer mortality risk (males) but decreasing respiratory disease mortality risk (males). The J‐shaped observational association between BMI and mortality was visible with MR analyses, but the BMI at which mortality was minimized was lower and the association was flatter over a larger BMI range.ConclusionsResults support a causal role of higher BMI in increasing the risk of all‐cause mortality and mortality from several specific causes.

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DO - 10.1002/oby.22313

M3 - Article (Academic Journal)

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BMI and Mortality in UK Biobank: Revised Estimates Using Mendelian Randomization

Abstract

Structured keywords

UN SDGs

Access to Document

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Projects

IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

Profiles

Professor Nicholas John Timpson

Cite this