obesity nutrigenomic

1. Obesity, Nutrition,
Nutrigenonmics – OH MY!
Karen L. Edwards, Ph.D.
Director, UW Center for Genomics and
Public Health
Department of Epidemiology and Institute for
Public Health Genetics
School of Public Health and Community Medicine
University of Washington

2. Objectives
1. Be familiar with the evidence for genetic
influences on obesity
2. Be able to define nutrigenomics
3. Understand current limitations of
nutrigenomic testing

3. Outline
1. Background
2. Genetics of Obesity
• Animals
• Humans
3. Environmental effects
4. Nutrigenomics
• Why the interest?
• Current products and examples
• Why the concern?
• Moving from promise to practice
5. Summary and Conclusions

4.  Mortality
 Increased risk of premature death
 Morbidity
 Diabetes, Heart disease, Hypertension, some Cancers,
Breathing Problems, Ischemic Stroke, Arthritis, and
Reproductive Complications
 Prevalence
 59 million (30%) Americans are obese (BMI>= 30)
 Rates are increasing faster than ever (epidemic proportions)
Public Health Importance

5. Risk Factors for Obesity
 Diet: high calorie and low nutrient dense foods
 Physical Inactivity
 Age
 Socioeconomic status
 Certain medical conditions and medications
 Race
 Smoking cessation
 Family History
 Genetic susceptibility

6. Evidence for Genetic Influences
on Obesity

7. Evidence for genetic
influences: Humans
• Familial aggregation
- familial clustering of obesity in families
• Twin Studies
- greater concordance among MZ twins
compared to DZ twins
• Family Studies
- variety of “statistical models” consistent with
genetic influences

8. The Search for Obesity Susceptibility Genes
“I found one! I found one!” Kenneth M. Weiss & Joseph D. Terwilliger
nature genetics • volume 26 • October 2000

9. Candidate Genes and Single Gene
Disorders: Chromosomal Location
Image adapted from:
Loos, R. J. and C. Bouchard (2003). J Intern Med 254(5): 401-25.

10. Genetics of Human Obesity
• Common form(s) of obesity are likely due to complex
interactions between genes and environment
- body fat pattern
- appetite regulation
- other pathways
• Rare monogenic forms do not account for majority of
cases

11. Trends in Obesity
From the CDC website: BRFSS Trends Data

12. Trends in Obesity
From the CDC Website: NHANES Study Data

13. Trends in Obesity

14. Nutrigenomics
Integrates genomics and nutrition
• Goal: Improving health and preventing disease through
tailored diet and lifestyle prescriptions

15. Nutrigenomics: Magic, Myths and Maybe’s

16. Nutrigenomics vs.
Nutrigenetics
Nutrigenomics
 “Nutrigenomics refers to the
application of genomics in nutrition
research, enabling associations to
be made between specific
nutrients and genetic factors, e.g.
the way in which food or food
ingredients influence gene
expression…Nutrigenomics
should facilitate greater
understanding of how nutrition
affects metabolic pathways and
how this process goes awry in
diet-related diseases.” Chadwick
R. (2004) Proceedings of the
Nutrition Society 63:161-166.
Nutrigenetics
 “Nutrigenetics is the study of
individual differences at the
genetic level influencing
response to diet. These
individual differences may be
at the level of single nucleotide
polymorphisms rather than at
the gene level…It is envisaged
that nutrigenetics may lead to
individualized dietary advice.”
Chadwick R. (2004) Proceedings
of the Nutrition Society 63:161-
166.

17. Nutrigenomics vs.
Nutrigenetics
Nutrigenomics
 “Nutrigenomics attempts to
study the genome-wide
influences of nutrition…[and]
aims to identify the genes that
influence the risk of diet-
related diseases on a genome-
wide scale, and to understand
the mechanisms that underlie
these genetic predispositions.”
Muller M & Kersten S. (2003)
Nature Reviews Genetics
4:315-322.
Nutrigenetics
 “Nutrigenetics examines the
effect of genetic variation on
the interaction between diet
and disease or on nutrient
requirements. Genetics has a
pivotal role in determining an
individual’s risk of developing a
certain disease.” Muller M &
Kersten S. (2003) Nature
Reviews Genetics 4:315-322.

18. Nutrigenomics vs.
Nutrigenetics
Nutrigenomics
 “Nutrigenomics describes the use
of functional genomic tools to
probe a biological system
following a nutritional stimulus that
will permit an increased
understanding of how nutritional
molecules affect metabolic
pathways and homeostatic
control.” Mutch D, et al. (2005)
FASEB Journal 19:1602-1616.
 “Nutrigenomics focuses on the
effect of nutrients on the genome,
proteome, and metabolome.”
Ordovas J & Mooser M. (2004)
Current Opinion in Lipidology
15:101-108.
Nutrigenetics
 “Nutrigenetics embodies the
science of identifying and
characterizing gene variants
associated with differential
responses to nutrients, and
relating this variation to disease
states.” Mutch D, et al. (2005)
FASEB Journal 19:1602-1616.
 “Nutrigenetics examines the effect
of genetic variation on the
interaction between diet and
exercise. This includes…gene
variants associated with, or
responsible for, differential
responses to nutrients.” Ordovas J
& Mooser M. (2004) Current
Opinion in Lipidology 15:101-108.

19. Nutrigenomics & Nutrigenetics:
Two Sides of a Coin
Mutch D, et al. (2005) FASEB
Journal 19:1602-1616.

20. Nutritional Genomics
The study of how different foods can interact with
particular genes to increase the risk of
diseases
such as type 2 diabetes, obesity, heart disease
and some cancers
Goal: Use of personalized diets to prevent or
delay the onset of disease and optimize and
maintain human health
http://nutrigenomics.ucdavis.edu/pressarticles.htm

21. Nutritional Genomics
van Ommen B. (2004) Nutrition 20:4-8.

22. Why the interest?
•Improve health of populations
• United States
• Globally
•Improve athletic performance
•Weight loss
•Potential economic impact
•Functional food and dietary supplements is
currently a $40 billion industry
•The focus on nutrigenomics could mean an
$80 billion dollar industry in 7-10 years

23. What is the evidence?
• Single Gene Disorders
•PKU
•Lactose intolerance
• Complex conditions
•Genes involved in susceptibility to complex
diseases have been identified
•Nutritional environment modifies the expression
of genes
•Metabolism of nutrients may vary by genotype,
ultimately affecting health

24. What is the public health
implication?
• Can we use this information along with our
increasing knowledge of the genetics of obesity for
public health applications?
•Obesity epidemic

25. Direct to Consumer Marketing
• Health Clubs
• Vending Machines
•Internet
•Retail stores

26. On the internet

28. Weight Loss
DNA Diet Builds Customized Weight-Loss Plan
One-size-fits-all diets could be a thing of the past.
NBC station KNSD in San Diego reported that a handful of bio-tech companies are
promising a high-tech recipe for losing weight and eating better. The newest weight-loss
plan is a customized diet based on your DNA. The DNA diet is a personalized meal plan
that claims to be based on your unique genetic blueprint.
Katzin claims that based on your DNA profile she can “determine
whether someone should increase the amount of folic acid, B-6 or B-12,
for example. So, we would choose foods that are rich in those
supplements.”
… “interprets the data and makes a customized meal plan. Her
suggestions range from “ taking more vitamins to eating more meat.”

29. Diet Design, One Pair of “Genes” at a Time
Health: You Are What You Eat
Oct. 31, 2005 issue - Bruce Morrill is something of a health
nut. So when his nutritionist suggested he take a $695 DNA
test so she could individualize his diet plan, Morrill, a 42-
year-old UPS driver from Reno, Nev., agreed.

30. Currently in the United States, no regulations are in place for evaluating the
accuracy and reliability of genetic testing. Most genetic tests developed by
laboratories are categorized as services, which the Food and Drug Administration
(FDA) does not regulate. This lack of government oversight is particularly
troublesome in light of the fact that a handful of companies have started
marketing test kits directly to the public. Some of these companies make dubious
claims about how the kits not only test for disease but also serve as tools for
customizing medicine, vitamins, and foods to each individual's genetic makeup.
(doegenomes.org)
Genetic testing to identify alleged risk factors that have no proven
corrective measures is simply a waste of money. As noted by Helen
Wallace, Ph.D., Deputy Director of GeneWatch UK: "For most people,
tailoring your diet to your genetic make-up is about as scientific as
tailoring your diet to your star sign."

31. Sciona
• International company previously based in the UK
•Personalized health and nutrition recommendations
•Products were available through retail stores
•GeneWatch UK called on retail stores to stop offering
these tests
•Currently based in Boulder, Colorado
•Launching a campaign in 4 test markets
•Partnerships with retail stores and local health care
system

32. In store sales

33. • Lund Foods CEO: “…plan is to create a link between the
evaluations performed by Sciona and his stores’ food
experts, which have long provided consumers with diet
and nutritional advice and information.”
• Today Food Editor: “The idea, which is a good one, is to
help shoppers understand what they can do in their daily
food choices to either maintain their good health or help
correct certain genetic defects that the test may have
identified.”

34. Heart Health
 “Analyzes thirteen of
your genes that may
play an important role
in determining how
your body manages
overall heart health”
 “…assesses nine key
diet and lifestyle
action areas”

35. Bone Health
 “Analyzes four of your
genes that may play
an important role in
determining how your
body manages overall
bone health
 “..assesses seven key
diet and lifestyle
action areas”

36. Insulin Resistance
 “Analyzes five of your
genes that may play
an important role in
determining how your
body manages overall
insulin resistance”
 “..assesses five key
diet and lifestyle
action areas”

37. Genetic Assessment for Antioxidant
and Detoxification
 “Analyzes six of your
genes that may play
an important role in
determining how your
body manages overall
antioxidant/
detoxification health”
 “..assesses four key
diet and lifestyle
action areas”

38. Inflammation
Health
 “Analyzes six of your
genes that may play
an important role in
determining how your
body manages
inflammation”
 “..assesses four key
diet and lifestyle
action areas”

40. Consumer Demand?
•Sciona claims to have sold 10,000 kits in Europe, Asia and
the US
•Current use is likely limited to those who can afford to pay
•HealthSyles Survey indicates that only 14% of US population
are aware of these tests, and only 0.6% have used a test
- age and income are associated with awareness
(Goddard et al., GIM 2007;9:510-7)

41. Currently in the United States, no regulations are in place for evaluating the
accuracy and reliability of genetic testing. Most genetic tests developed by
laboratories are categorized as services, which the Food and Drug
Administration (FDA) does not regulate. This lack of government oversight is
particularly troublesome in light of the fact that a handful of companies have
started marketing test kits directly to the public. Some of these companies
make dubious claims about how the kits not only test for disease but also
serve as tools for customizing medicine, vitamins, and foods to each
individual's genetic makeup. (doegenomes.org)
Genetic information is unlike other health information, in that it also provides
information about your family members
Genetic testing to identify alleged risk factors that have no proven corrective
measures is simply a waste of money. As noted by Helen Wallace, Ph.D.,
Deputy Director of GeneWatch UK: "For most people, tailoring your diet to
your genetic make-up is about as scientific as tailoring your diet to your star
sign."
Why the Concern?

42. “Buyer Beware”
A recent report by the Government Accountability Office
highlighted a few of the concerns with four examples of DTC
nutrigenomic tests. The GAO report raised concerns that
the tests may mislead consumers by making unsound and
ambiguous
predictions about health risks. In addition, the test
results frequently include recommendations for the consumer
to purchase dietary supplements that may be significantly
overpriced compared with similar products available through
a supermarket or pharmacy and that may, in fact, be harmful
for some individuals.

43. Potential Benefits
•Increased focus on a healthy diet and lifestyle
•Motivate positive behavior change
•Increased awareness of risk of certain conditions
•Improved health and quality of life
•Focus on prevention
•Decreased morbidity and premature mortality
•Reduced health care costs
•Identify subgroups who might be particularly responsive or
resistant to environmental (dietary) intervention
• Better understanding of the mechanisms involved in
disease susceptibility

44. Potential Harms
•Attention is drawn away from other modifiable risk
factors
•Decreased use of other services
•False sense of security
•Focus on specific nutrients/foods
•Ineffective or harmful
•Misleading claims
•Dilute or contradict public health messages

45. Potential Harms, cont.
•Increased costs associated with personalized
diets and designer foods
•Targeting vulnerable populations
•Concerns surrounding confidentiality, insurance
•Biobanking of samples, informed consent
•Unintended consequences

46. From Promise to Practice
•Consistent evidence
•Evidence for clinical utility – added value
•Understand how information is used
•Culturally specific translation
•Thoughtful integration based on evidence
•Holistic approach
•Address ELSI issues prior to integration
•Access to services and “treatment”

47. Summary
•Potential is exciting
•Range of opinions regarding readiness of current
applications
•Many parallels to pharmacogenomics
•Dr. Arno Motulsky: “ the total promise of PGX is
often overstated and is unlikely to lead to a
revolution in therapeutics”
•May provide benefits to some individuals, but probably
not as broadly as currently predicted

48. Conclusions
•Obesity is influenced by both genes AND
environment
•Obesity is associated with poverty, SES and
education
•Diet is important
•High-fat energy-dense foods are often the
cheapest options for the consumer
•Health foods cost more
•Nutrigenomic testing is not ready for prime time

49. UW Center for Genomics
and Public Health
http://depts.washington.edu/cgph
Funded as part of the ASPH/CDC/ATSDR
cooperative agreement
Office of Genomics and Disease Prevention
Centers for Disease Control and Prevention