Module 2.4

1. Gene and Environment
Interactions

2. Genes
 To date, genome-wide association studies
have identified more than 30 candidate
genes on 12 chromosomes that are
associated with body mass index.
 It’s important to keep in mind that even
the most promising of these candidate
genes, FTO, accounts for only a small
fraction of the gene-related susceptibility
to obesity.
http://www.hsph.harvard.edu/obesity-prevention-source/obesity-causes/genes-and-obesity/

3. The increased global prevalence of obesity
could not be driven by genes alone
 Substantial changes in the gene pool takes thousands of
years to accumulate and affect the phenotype of a
population
 Obesity epidemic is occurring on genetic backgrounds that
have not changed
 Genetic factors likely confer susceptibility in a permissive
environment
 “susceptibility” genes that underlie the propensity to develop
obesity
 Genes that regulate distribution of body fat, metabolic
rate, response to exercise and diet, and control feeding
and food preferences
AHA Scientific Statement Circulation 2006;113:898-918

4. Gene Environment Interactions
 Obesity results from a complex interplay of many genetic
factors and environmental factors. In epidemiology,
interaction is defined by estimating whether the degree
of risk attributable to the joint effects of a genotype and
an environmental factor on an outcome is greater or less
than would be expected if these joint effects were
additive.
 Alternatively, GEI exists where the risk conveyed by
specific genotype depends on one or more
environmental exposure levels. This definition is quite
helpful in the context of intervention studies where the
environmental exposures can be intervened upon, such
as diet and physical activity, to offset genetic risk.
http://bmcmedgenomics.biomedcentral.com/articles/10.1186/1755-8794-8-S1-S2

5. Nutrigenomics and
Nutrigenetics
 Nutrigenomics explores the effects of nutrients or other dietary
factors on the gene expression, DNA methylation, proteome and
metabolome, while nutrigenetics is aimed to elucidate whether
genetic variations modify the relationships between dietary factors
and risk of diseases.
 Nutrigenetics is a special area of GEI research, where the
environmental exposure is consumption of specific foods or
nutrients.
 Nutrigenetics has the potential to provide scientific evidence for
personalized dietary recommendations based on the individual’s
genetic makeup for weight control. Looking from a different
perspective, nutrigenetic studies also assess whether genetic factors
modify the effects of specific dietary factors on diseases or related
traits.
http://bmcmedgenomics.biomedcentral.com/articles/10.1186/1755-8794-8-S1-S2

6. Gene-environment interaction
in the pathogenesis of obesity
Although genetics is an important factor in the pathogenesis of obesity, the
recent increase in obesity cannot be attributed to genetics alone and must be a
result of alterations in environmental influences.
However, people with certain genetic backgrounds are particularly predisposed
to weight gain and obesity-related diseases, especially when they are exposed to
a precipitating lifestyle. A striking example of this is given by the Pima Indians of
Arizona. Lifestyle changes have resulted in an epidemic of obesity and diabetes
within this population during the last 50 years [1].
Today, the Pimas of Arizona consume a high-fat diet (50% of energy as fat)
provided by government surplus commodities rather than their traditional low-fat
diet (15% of energy as fat), and they are much more sedentary than when they
were farmers.
In contrast, Pima Indians who live in the Sierra Madre mountains of Northern
Mexico, and consequently who have been isolated from Western influences, eat
a traditional Pima diet and are physically active as farmers and sawmill workers.
The Pimas of Mexico have a much lower incidence of obesity and diabetes than
their genetic kindred in Arizona.

7. 0
10
20
30
40
50
Gene-Environment Interaction
in the Pathogenesis of Obesity
BodyMassIndex(kg/m2)
Ravussin E et al. Diabetes Care 1994;17:1067-1074.
Pima Indians
Maycoba, Mexico Arizona
P <0.0001

8. Gene-environment interaction in the
pathogenesis of obesity
 People with certain genetic backgrounds are particularly predisposed to
weight gain and obesity-related diseases, especially when they are
exposed to a precipitating lifestyle.
 A striking example of this is given by the Pima Indians of Arizona.
Lifestyle changes have resulted in an epidemic of obesity and diabetes
within this population during the last 50 years [1]. Today, the Pimas of
Arizona consume a high-fat diet (50% of energy as fat) provided by
government surplus commodities rather than their traditional low-fat diet
(15% of energy as fat), and they are much more sedentary than when
they were farmers.
 In contrast, Pima Indians who live in the Sierra Madre mountains of
Northern Mexico, and consequently who have been isolated from
Western influences, eat a traditional Pima diet and are physically active
as farmers and sawmill workers. The Pimas of Mexico have a much lower
incidence of obesity and diabetes than their genetic kindred in Arizona.
1. Pratley RE. Gene-environment interactions in the pathogenesis of type 2 diabetes mellitus: lessons learned from the Pima
Indians. Proc Nutr Soc. 1998;57:175-181.
2. Ravussin E et al. Effects of a traditional lifestyle on obesity in Pima Indians. Diabetes Care 1994; 17:1067-1074