Kari E' North, MA PhD

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The Genetic Epidemiology of Cardiovascular
Disease Risk Factors Obesity
Kari E. North, MA PhD Associate
ProfessorDepartment of Epidemiology Carolina
Center of Genome Sciences
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Increase in Prevalence () of Obesity Among US
Adults
Source CDC, National Center for Health
Statistics, National Health and Nutrition
Examination Survey.
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Obesity is a Major Public Health Burden

• Increases risk of illness
• Increases in deaths from all-causes
• Second only to smoking as a contributor to
  illness and premature death
• Increases obesity-related diseases in children
  and adolescents
• Higher risk for impaired mobility
• Social stigmatization and discrimination

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Obesity Thrifty Genotype Hypothesis

• Strong support for familial aggregation
• Prevalence of obesity twice as high in families
  of obese individuals than population at large
• Monogenic forms of obesity have been found in
  human populations, although extremely rare
• SNP associations (FTO, INSIG2, PPAR?)
• We have the right genes in the wrong
  environment (Rosmond 2004)

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Genetic Effects Work in Context
Genotype
Toxic exposures
Nutrition
Lifestyle
vs.
Phenotype
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Genome Wide Association Studies

• Method for interrogating all 10 million variable
  points across the human genome
• Variation inherited in groups (blocks), thus not
  all 10 million points have to be tested
• Indirectly test multiple variants genome-wide
  without any prior hypothesis
• Is genetic variation associated with given
  phenotype?

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Charge Consortium Cohorts for Heart and Aging
Research in Genomic Epidemiology
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Charge Consortium Preliminary Results from
Meta-Analysis of BMI
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Genetic Epidemiology Research Implications

• To improve understanding of disease
  pathophysiology in a manner that suggests new
  directions for therapy
• Identify individuals who are at increased risk of
  disease and allow tailoring of lifestyle choices
  to specific risk factors
• To identify subclasses of clinically similar
  diseases that nevertheless have different genetic
  etiologies and thus might respond favorably to
  different therapies

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Acknowledgements

• North Lab
• Christy Avery
• Daniel Canos
• Nora Franceschini
• Dick Howard

• Xia Li
• Keri Monda
• Amy Mottl
• Yu Yan