Study of 500,000 people clarifies the risks of obesity

Elevated body mass index (BMI)
– a measure of weight accounting for a person’s height – has been shown to be a
likely causal contributor to population patterns in mortality, according to a
new study led by the University of Bristol using measurements and mortality
data from 500,000 people. Specifically, for those in UK Biobank (a study of
middle to late aged volunteers), every 5kg/m² increase in BMI was
associated with an increase of 16 per cent in the chance of death and 61 per
cent for those related to cardiovascular diseases. The work is published on 25 October in Obesity
Editors’ Choice.

While it is already known that
severe obesity increases the relative risk of death, previous studies have
produced conflicting results with some appearing to suggest a protective effect
at different parts of the spectrum of body mass index. Until now, no study has
used a genetic-based approach to explore this link.

The Bristol team applied a
method called Mendelian randomization, a technique that uses
genetic variation in a person’s DNA to help understand the causal relationships
between risk factors and health outcomes – here mortality. This method can
provide a more accurate estimate of the effect of body mass index on mortality
by removing confounding factors, for example, smoking, income and physical activity,
and reverse causation (where people lose weight due to ill health), which could
explain the conflicting findings in previous observational studies.

Using data from the UK Biobank, the team were able to show that
the apparent optimum body mass index for survival was lower with Mendelian
randomization analyses (within the normal weight rather than overweight range
found with observational studies) and the association remained flatter over a
larger range of body mass index.

The findings which link body
mass index and mortality, confirm that being overweight increases a person’s
risk of death from all causes including cardiovascular diseases and various
cancers.

Dr Kaitlin Wade, Research Associate in Genetic
Epidemiology at the Bristol Medical School (Population Health Studies)
and lead author of the study, said:

“The findings highlight the need for a
global effort to reduce the surging levels of obesity within society and
suggest that in most cases, any reduction in body mass index to a normal,
healthy level is likely to be beneficial.”

This research was supported by
the Wellcome Trust and included researchers associated with the Medical
Research Council Integrative Epidemiology Unit, the Cancer Research UK
Integrative Cancer Epidemiology Programme, the University of Bristol Population
Health Sciences Institute and the University of Bristol NIHR Biomedical
Research Centre.

Paper

‘Body mass index and mortality in UK Biobank: revised estimates using Mendelian randomization’ by K Wade et al
in Obesity