Genetics and Population Health

Genetics and Population Health How Genes Influence Health • Determine effect--dominant or recessive genes—single gene causes disease – Examples: Huntington Chorea, sickle cell disease • Influences likelihood – specific diseases—e.g. breast cancer – Groups of diseases e.g. opportunistic infections • Influences risk factors—e.g. high blood pressure, • Influences health behaviors e.g. tobacco use • Influences health care behaviors . J Fielding Health Determinants April 2005 Genetic Influences on Health Behaviors and Risks • Influences health behaviors – E.g. consumption of alcoholic beverages – E.g. tobacco use – E.g. thrill seeking behavior—e.g. motorcycle riding • Influences health risks – E.g. risk of motor vehicle injury if have Attention Deficit Disorder J Fielding Health Determinants April 2005 Genetic Influences on Health Care Relevant Behaviors • Health seeking behavior – E.g. likelihood of receiving preventive services – E.g. hypochrondriasis or fear of particular diseases • Choice of intervention options – E.g. surgery vs medical Rx for prostate cancer • Compliance with medical recommendations – E.g. taking medication as directed • Compliance with public health recommendations – E.g. avoiding mosquito infested areas during West Nile season – E.g. wearing safety belts J Fielding Health Determinants April 2005 Genetic Influences on Health Conditions and Diseases • Injuries – Low contribution e.g. drive by shooting injuries; tripping on ice patch – Moderate contribution e.g. instigating road rage fight; fall while hiking alone in deep wilderness – High e.g. motor vehicle collision while intoxicated; J Fielding Health Determinants April 2005 Genetic Contribution to Health Risks • How would you determine the genetic contribution to: • • • • • • Tobacco use Other drug use Overweight and obesity Physical activity High blood pressure High blood lipids J Fielding Health Determinants April 2005 Exploring the Common Perception • ―Genes are the primary determinant of present and future health status.‖ • Important determinant of health for everyone, however-• Very small portion of disease burden can be traced to single gene – E.g. PKU, sickle cell, hemophilia • Most major diseases result from gene-gene interaction and/or from gene-environment interaction J Fielding Health Determinants April 2005 ―Genetic Diseases‖ cause a small portion of overall disease burden J Fielding Health Determinants April 2005 Respective Role of Genetics J Fielding Health Determinants April 2005 What influences gene expression? • Period of development e.g. prenatal, infant, child • Interaction with other genes – One turns another on – They perform a joint function • Exposure to environmental factors – – – – – Air Water Food Pesticides, herbicides etc. Pharmaceutical products • Interaction with multiple genes and environmental factors J Fielding Health Determinants April 2005 Development of Phenotype • Complex network of with inputs – Multiple genetic loci – Multiple environmental influences • Parallel and redundant pathways • Feedback loops • Compensatory pathways (one adjusts for inadequacies in other) J Fielding Health Determinants April 2005 Diseases caused by gene environmental interactions • Type II diabetes • Auto-immune diseases – E.g lupus, rheumatoid arthritis • Alzheimers in those with head injury – Only if individuals has genotyhpe with at least one ApoE Epsilon 4 allele (Mayeux et al 1995) • Estrogen protective for cognitive failure in women over 65, but only if have Apo E epsiolon 2 or 3 allele—thus environmental protection predicated on genetic makeup J Fielding Health Determinants April 2005 Elevated Blood Pressure • Investigated relative contribution of genetic and environmental factors • Review: genetic factors account for 30-60% of variance in blood pressure • African-Americans have higher rates of hypertension than Caucasians – However, a large portion of individual variability in blood pressure for adults arose from genetic sources – Based on twin studies heritabilities were .44 for diastolic and .52 for systolic – Thus at least ½ or more of variation due to environmental factors J Fielding Health Determinants April 2005 Variation among Racial Groups • Study (Nei, 1975) – What is total genetic variation of Caucasoid, Negroid and Mongoloid racial groups – Examined protein electrophoretic phenotypes – Results: • 7% attributable to differences among groups • 93% attributable to differences within each group – Demonstrates low predictive value based on race J Fielding Health Determinants April 2005 Single Nucleotide Polymorphisms (SNPs) • Subject of great scientific interest • Single DNA bas pair—occur every 1000 bases – Coding regions—may alter proteins – Non-coding regions—could influence regulation of gene expression • Study to understand differences across racial/ ethnic groups J Fielding Health Determinants April 2005 SNPs and other genetic markers • Most findings suggest that for most diseases with racial/ ethnic differences, a significant fraction is due to variation within a particular group, suggesting the importance of environmental factors e.g. high blood pressure J Fielding Health Determinants April 2005 Gene/ Environment Contributions • Evidence for genetic component to many diseases • But, remember the twin studies— • Why less than 100% concordance in monozygotic twins? • Migration studies – Japanese to Hawaii to mainland U.S. – Latin American immigrants to U.S. J Fielding Health Determinants April 2005 Genetic Testing: Promises • Many organizations offering genetic testing for large number of genes – Over 900 genes known • However, few genes identified have direct health effects • For most genes, unknown ability to modify effects J Fielding Health Determinants April 2005 Criteria for Choosing Genetic Tests • Disease/ condition is important public health problem • Scientific data document occurrence of the genetic trait and the burden of disease associated with the trait • Natural history of disease is understood • Test is safe, effective and has high predictive value J Fielding Health Determinants April 2005 Criteria • Target population finds it acceptable • Screening, counseling, follow-up and effective intervention are available, acceptable and safe • Safeguards assure informed consent and voluntary testing, protect the private of individuals, and deter stigmatization and discrimination • Benefits of screening outweigh the harms J Fielding Health Determinants April 2005