Transcript Chapter 16 - Illinois State University

 Genetic
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Influences
Obesity and Genomics
 Obesity
results when body fat
accumulates over time as a result of a
chronic energy imbalance (calories
consumed exceed calories expended).
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Obesity and Genomics
 Obesity
is a major health hazard
worldwide and is associated with
several relatively common diseases
such as diabetes, hypertension, heart
disease, and some cancers.
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The “obesity epidemic” – can genes really
be involved?

In recent decades, obesity has reached
epidemic proportions in populations whose
environments offer an abundance of calorierich foods and few opportunities for physical
activity.

Although changes in the genetic makeup of
populations occur too slowly to be responsible
for this rapid rise in obesity, genes do play a
role in the development of obesity.
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The “obesity epidemic” – can genes really be
involved?
 Most
likely, genes regulate how our
bodies capture, store, and release
energy from food.
 The
origin of these genes, however,
might not be recent.
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How might genes contribute to obesity?
A “thrifty genotype” hypothesis

Any explanation of the obesity epidemic has to
include both the role of genetics as well as that
of the environment.

A commonly quoted genetic explanation for
the rapid rise in obesity is the mismatch
between today’s environment and "energythrifty genes" that multiplied in the past under
different environmental conditions when food
sources were rather unpredictable
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How might genes contribute to obesity?
A “thrifty genotype” hypothesis
.
In other words, according to the
"thrifty genotype" hypothesis, the same
genes that helped our ancestors survive
occasional famines are now being
challenged by environments in which
food is plentiful year round.
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What other ways might genes influence
obesity?

It has been argued that the thrifty genotype is
just part of a wider spectrum of ways in which
genes can favor fat accumulation in a given
environment.

These ways include the drive to overeat (poor
regulation of appetite and satiety); the
tendency to be sedentary (physically inactive);
a diminished ability to use dietary fats as fuel;
and an enlarged, easily stimulated capacity to
store body fat.
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What other ways might genes influence
obesity?

Not all people living in industrialized countries with
abundant food and reduced physical activity are or
will become obese; nor will all obese people have the
same body fat distribution or suffer the same health
issues.

This diversity occurs among groups of the same
racial or ethnic background and even within families
living in the same environment
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What other ways might genes influence
obesity?

The variation in how people respond to the same
environmental conditions is an additional indication
that genes play a role in the development of obesity.

This is consistent with the theory that obesity results
from genetic variation interacting with shifting
environmental conditions.
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What do we know about specific genes
associated with obesity?
 The
indirect scientific evidence for a
genetic basis for obesity comes from a
variety of studies.
 Mostly,
this evidence includes studies
of resemblance and differences among
family members, twins, and adoptees
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What do we know about specific genes associated
with obesity?
 Another
source of evidence includes
studies that have found some genes at
higher frequencies among the obese
(association studies).
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What do we know about specific genes associated
with obesity?
 These
investigations suggest that a
sizable portion of the weight variation
in adults is due to genetic factors.
 However,
identifying these factors has
been difficult.
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What do we know about specific genes
associated with obesity?
 Regarding
the direct evidence for obesity
genes, the best success stories come from
several cases of extreme obesity due to
mutations (changes in the genetic
material) of single genes (monogenic
cases).
 But
those cases account for only a very
small fraction of cases worldwide.
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What do we know about specific genes associated
with obesity?
 More
recently, however, mutations in a
single gene (Melanocortin 4-receptor
gene, related to the control of feeding
behavior) have been found to be
strongly associated with a minority
(perhaps 5%) of obesity cases in several
populations.
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What do we know about specific genes associated
with obesity?

Progress in identifying the multiple genes
associated with the most common form of obesity
has been slow but is accelerating.

As of October 2005 (the latest update of the Human
Obesity Gene Map), single mutations in 11 genes
were strongly implicated in 176 cases of obesity
worldwide.

Additionally, 50 chromosomal locations relevant to
obesity have been mapped, with potential causal
genes identified in most of those regions.
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What do we know about specific genes associated
with obesity?

Chromosomes are threadlike structures that contain
the genes densely packed into the nucleus of each
cell.

Also, studies using genome-wide scans have focused
on 253 groups of genes related to obesity, with about
one-fifth of them reported by two or more studies.
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What do we know about specific genes associated
with obesity?

Genome is the total number of genes contained in the
chromosomes.

Finally, 426 variants of 127 genes have been
associated with obesity.

At least five independent studies have replicated
each association in 22 of these genes.
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What do we know about specific genes associated
with obesity?

Recently, several independent population-based
studies report that a gene of unknown function (FTO,
fat mass and obesity-associated gene) might be
responsible for up to 22% of all cases of common
obesity in the general population.
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What do we know about specific genes associated
with obesity?
 Interestingly,
this gene also shows a
strong association with diabetes.
 The
mechanism by which this gene
operates is currently under intense
scientific investigation
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How can public health genomics help reduce the
impact of obesity in populations?
 Scientists
have made great advances in
understanding important environmental
causes of obesity as well as identifying
several of the many genes that might be
implicated.
 Major
efforts are now directed toward
assessing the interactions of genes and
environment in the obesity epidemic
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How can public health genomics help reduce the
impact of obesity in populations?
 The
translation of these efforts into
public health practice, from a genomic
point of view, will take time.
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…and how can family history help?
 Fortunately,
there is a simple way for
public health genomics to start reducing
the effects of obesity in populations.
 It
is through the use of family history.
Family history reflects genetic
susceptibility and environmental
exposures shared by close relatives.
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…and how can family history help?

Health care practitioners can routinely collect family
health history to help identify people at high risk of
obesity-related disorders such as diabetes,
cardiovascular diseases, and some forms of cancer.

Weight loss or prevention of excessive weight gains
is especially important in this high-risk group.
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…and how can family history help?

Any health promotion effort to reduce the adverse
impact of obesity in populations may be more
effective if it directs more intensive lifestyle
interventions to high-risk groups (high-risk
prevention strategy).
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…and how can family history help?

However, such strategies should not detract from the
population prevention strategy, which recommends
that regardless of genetic susceptibility and
environmental exposure, all people should follow a
healthful diet and incorporate regular physical
activity into their daily routine to help reduce the risk
of obesity and its associated conditions.
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Genetic Effects
Body
Composition
Necessary
Genes
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Susceptibility
Genes
Gene-Gene
Interactions
Gene-Environment
Interactions
Other
Affectors
Genetic Effects
A
susceptibility gene is one that
increases susceptibility or risk for a
disease but is not necessary for disease
expression.
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Genetic Effects
A
necessary gene is one that is sufficient
to cause the disease if the deficient trait
has been inherited.
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Genetic Effects
 Gene-gene
interactions occur when one
gene triggers the action in another gene
to cause a trait to exist.
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Genetic Effects
 Gene-environment
interactions occur
when environmental conditions (e.g.,
diet, exercise) trigger the gene to bring
about the trait.
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Heritability
 The
heritability of BMI is in the range of
40-70%.
 The
heritability for body fat is in the
range of 25-40%.
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Heritability
 Clear
evidence for a specific maternal or
paternal effect is lacking, and the
common familial environmental effect
is marginal.
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Adipose Tissue Topography
 Upper
body obesity is more prevalent
in males than in females, and it
increases in frequency with age in
males and after menopause in females.
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Adipose Tissue Topography
 There
is a significant genetic influence
on central deposition of adipose tissue.
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Adipose Tissue Topography
 Assuming
that all transmissible effects
are genetic, results suggest that heredity
accounts for a maximum of 40% of the
phenotype variance for various
indicators of adipose tissue topography.
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Muscle Composition
Familial
Resemblance
 FFM
Yes
 Est. muscle Yes
mass
 Nutrient
Yes
partitioning
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Estimated
Heritablity
30%
40%
20%
Muscle Composition
 Fiber
type
 Oxidative
potential
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Familial
Estimated
Resemblance Heritablity
Yes
6-100%
Yes
<50%
Bone Composition
A
significant genetic effect exists in
determining the length of individual
long bones (~92%).
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Summary
 In
the last decade or so, genetic
epidemiology research has shown that
body fat and adipose tissue topography
phenotypes are generally characterized
by the contribution of a multi-factorial
transmitted component as well as a
major recessive gene effect.
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Summary
A
major gene effect has been detected
for FFM.
 Corresponding analyses are apparently
lacking for skeletal characteristics and
physique components.
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Summary
 There
is growing evidence that the
genetic component of body composition
and physique phenotypes will
eventually be defined in terms of a
series of contributing and interacting
genes.
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