The Genetics of Obesity
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Learning Outcomes
• Identify the extent to which genes impact
on a person becoming obese
• Discuss the difference between monogenic
and polygenic obesity
• Identify some of the mechanisms by which
genes influence a persons risk of becoming
obese
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Causes of obesity activity
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Place these causes of obesity into the pyramid with most
important at the top , some will have equal importance, some
will be more important, some will have to be left out
Food company advertising
Lack of safe play areas
Expense of healthy food
Not being taught how to cook in school
Not being taught how to cook at home
Inexpensive fast food
Children spending excessive time on
computers/watching television
Decline in manual labour
Genetics
Increased car ownership
Increase in out of town shopping centres
Availability of food
Individual greed and laziness
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
The impact of genes on the risk of obesity
• Obesity is a complex multifactorial condition
• Determinants of obesity in an individual are not necessarily those
that drive the increase in the population
• Extreme rise in prevalence indicates environmental rather than
genetic causes
• However some individuals maintain a healthy weight despite an
obesogenic environment
• Genetic differences between individuals account for 40 -70% of
differences between individuals within populations (PHG
Foundation, 2013)
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Genes implicated in common obesity
• Research has found 50 loci to be associated with BMI,
waist-hip ratio, percentage body fat and morbid obesity.
• Sizes of the established loci are small, and combined they
explain only a fraction of the inter-individual variation in
BMI
• Low predictive value therefore value in healthcare is
limited (Day and Loos, 2011).
• Physical activity attenuates the BMI-increasing effect of
some of the genes.
• Some genetic alterations have been identified as having
an impact on how an individual might feel hungry or feel
full following eating
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
• One of the most commonly cited genes in relation to
obesity is the FTO gene.
• FTO regulates the hormone ghrelin, which is an
appetite hormone responsible for eating behaviour.
• Ghrelin stimulates hunger and increases food intake.
Ghrelin reduces the sense of fullness after eating,
causing further eating, and it also causes a
preference for high fat foods.
• High-risk variant of the FTO gene actually works in an
epigenetic way by removing methyl groups from the
ghrelin gene, causing it to produce more ghrelin
(Karra et al., 2013).
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
• 50% of the UK population are more likely to be
obese because they have a particular variant of
the melanocortin receptor gene MC4R
(Chambers et al., 2008).
• The variant is more common in people of
Indian-Asian ancestry which may partly explain
high rates of obesity in this group.
• These gene variants also make people more
likely to develop insulin resistance and type 2
diabetes.
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Monogenic Obesity
Rare single-gene disorders where severe obesity
is the primary feature
There are forms of severe, young-onset obesity
caused by a defect in a single gene, although
these are very rare in the population as a whole.
Examples are deficiencies involving the hormones
melanocortin and leptin which have a key role in
regulating appetite and metabolism (Farooqi and
O’Rahilly, 2007).
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Rare genetic syndromes where obesity is an
associated feature
Some rare familial syndromes have obesity as
one of many features, often associated with
mental impairment, dysmorphic features and
developmental abnormalities: e.g. Prader Willi
syndrome, Alstrom syndrome and Fragile X
syndrome (Farooqi and O’Rahilly, 2007).
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
References
• Foresight. Tackling Obesities: Future Choices.
Project Report. London, UK: Government Office
for Science, 2007.
• National genetics and Genomics Education
Centre. Obesity and Genetics Factsheet.
http://www.geneticseducation.nhs.uk/search/it
em/29-0029-genetics-and-obesity
• PHG Foundation. Genomics of Obesity: The
Application of Public Health Genomics to the
Prevention and Management of Obesity in the
UK, 2013.
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk