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Human Variation, Health Disparities, & “Race”: What we know and what we don’t know

Human Variation, Health Disparities, & “Race”: What we know and what we don’t know Richard S. Cooper, MD Department of Preventive Medicine Loyola Stritch School of Medicine . Health Status Measures in US Racial/Ethnic Groups, 1998. White Black Hispanic Asian.

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Human Variation, Health Disparities, & “Race”: What we know and what we don’t know

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  1. Human Variation, Health Disparities, & “Race”: What we know and what we don’t know Richard S. Cooper, MD Department of Preventive Medicine Loyola Stritch School of Medicine

  2. Health Status Measures in US Racial/Ethnic Groups, 1998 White Black Hispanic Asian Cause of DeathAge – Adjusted Death Rates 450.4 121.9 79.2 23.3 121.0 21.9 12.7 12.0 2.6 690.9 183.3 92.5 41.4 161.2 17.7 17.4 28.8 20.6 432.8 84.2 54.7 19.0 76.1 8.5 9.8 18.4 6.2 264.6 67.4 42.9 22.7 74.8 7.4 10.3 8.7 0.8 All Causes Hearth Disease Coronary Heart Disease Stroke Cancer COPD Pneumonia / Influenza Diabetes mellitus HIV infection Infant Mortality (/1000) Life Expectancy 6.0 77.3 13.6 71.3 5.8 >80? 5.5 >80?

  3. Health Status Measures in US Racial/Ethnic Groups 200 20 150 15 100 Death Rate per 100,000 10 Infant Mortality per 1,000 50 5 0 Heart Disease 0 Stroke Hispanic Asian White Black Cancer Diabetes Mellitus HIV Infection External Causes Infant Mortality

  4. Infant Mortality by Race/Ethnicity US, 1995 - 1998 16 Blacks 14 12 American Indians 10 8 Whites 6 Asian 4 1995 1996 1997 1998

  5. Low Birthweight and Very Low Birthweight; White, Blacks and Hispanics; US, 1990 - 2000 Blacks Whites Hispanics Very Low Birthweight Low Birthweight 14 3.5 3.0 12 2.5 10 2.0 8 1.5 6 1.0 0.5 4 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991 1990 1989 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991 1990 1989

  6. Percentage of U S children age 1 – 5 with blood lead > 10 mg/dl* Percent White 2.3 Black 11.2 Mexican-American 4.0 *NHANES III

  7. Hypertension in HDFP, by Race and Education 50 40 30 20 10 Whites Blacks % Hypertensive (DBP  95 mmHg) 0 < 10 10-11 12 Some College years years years College Grad Educational Level

  8. Ethnic and Socioeconomic Differences in Cardiovascular Disease Risk Factors Winkleby et al. JAMA, 1998;280-356-362 “To our knowledge, this article is one of the first to document higher levels of CVD risk factors among black and Mexican American women than among white women of comparable age and SES. We hypothesized that ethnic minority status would be associated with higher levels of CVD risk factors, but that the associations would be explained substantially by SES. Our hypothesis was not confirmed….”

  9. The CDC Office of Genetics and Disease Prevention Provides a Press Release.. The elevated risk of CV disease in minority women, long thought to be primarily the result of SES, may well be more closely related to race than once believed, researchers at Stanford report this week in JAMA. Differences in blood pressure, body mass index and diabetes persisted.. even after adjusting for years of education, indications that race itself plays a role.. (leading) the researchers to say that genetic factors may come into play.

  10. SES, Race and Mortality Age-Adjusted Death Rate SES vs. Death Rate Blacks Whites Black % White Power/Wealth/Privilege

  11. Race and Mortality, Expected Results After Adjustment for SES Age-Adjusted Death Rate SES vs. Death Rate Whites Blacks Black % White Power/Wealth/Privilege

  12. Race and Mortality, Actual Results After Adjustment for EDUCATION Age-Adjusted Death Rate SES vs. Death Rate Blacks Whites Black % White Power/Wealth/Privilege

  13. Rates of Low Birthweight in Blacks & Whites, by Education: Georgia , 1980 - 87 180 160 140 120 100 80 60 40 20 0 Blacks Whites Low Birth WT (%) 12 <12 >12 Years of Education

  14. Rates of Low Birthweight in Blacks, by Education & Marital Status 200 180 160 140 120 100 80 60 40 20 0 Unmarried Married Low Birth WT / 1,000 <12 12 >12 Years of Education

  15. Rates of Low Birthweight in Whites, by Education & Marital Status 180 160 140 120 100 80 60 40 20 0 Unmarried Low Birth WT / 1,000 Married 12 <12 >12 Years of Education

  16. H y p e r t e n s i o n d e f i n e d a s S y s t o l i c B l o o d P r e s s u r e > 1 4 0 o r D i a s t o l i c B l o o d P r e s s u r e > 9 0 o r t a k i n g A n t i - h y p e r t e n s i o n M e d i c a t i o n Prevalence of Hypertension Among Six Populations of West African Origin: ICSHIB, 1995 0 . 4 0 0 . 3 5 0 . 3 0 0 . 2 5 Percent Hypertensive 0 . 2 0 0 . 1 5 0 . 1 0 0 . 0 5 0 . 0 0 M a y w o o d B a r b a d o s J a m a i c a S t . L u c i a C a m e r o o n N i g e r i a

  17. 35 Chicago, IL 30 Barbados St. Lucia 25 Jamaica Percent Hypertensives 20 Cameroon Urban Nigeria 15 Cameroon Rural 10 22 24 26 28 30 32 Body Mass Index Hypertension by Body Mass Index Among Populations of West African Origin: ICSHIB, 1995

  18. Hypertension Prevalence in the US, Canada, and Europe, by Age Group 100 90 80 70 60 Hypertension Prevalence (%) 50 40 Germany Finland 30 Spain Italy England 20 Sweden USA 10 Canada 0 35-<45 45-<55 55-<65 65-<75 Age (years)

  19. Age- and Gender- Adjusted Hypertension Prevalence, by Country and Race* 60 50 40 Hypertension Prevalence (%) 30 20 10 0 Nigeria Jamaica US White Sweden Italy England US Black Spain Finland Germany *Ages 35-64

  20. Lesser Response of ACE-I in Blacks Exner et al NEJM, 2001 Death from Any Cause (%) Hospitalization for Heart Failure (%)

  21. Heart Failure and Race . . . Heart failure in blacks is a unique malady characterized by a different natural history, more worrisome prognosis, and potential variances in the response to current medical therapy for heart failure … Certain genetic polymorphisms may exist that explain the observed differences. C.Yancy, “The Role of Race in Heart Failure Therapy”. Curr Cardiol Rep 2002

  22. Relative Risk, Enalapril vs. Placebo for Progression to Heart Failure, SOLVD Blacks RR (95% CI) 0.67 (0.49-0.92) 0.71 (0.54-0.95) 0.83(0.60-1.16) Whites RR (95% CI) 0.61(0.53-0.70) 0.70 (0.62-0.78) 0.82 (0.71-0.94) Heterogeneity of Effect Unadjusted P-value 0.50 0.72 0.71 Adjusted P-value 0.66 0.74 0.82 Development of Symptoms of Heart Failure Death or Development of Symptoms of Heart Failure Death or First Hospitalization for Heart Failure Dries, et al JACC, 2002

  23. Trends in the Number of Black Men in College and in Prison 9* 8 7 6 In College 5 4 In Prison 3 2 1 0 *x 106 1980 1992 2000

  24. The Biological Determinist Hypothesis as Applied to Race Genotype* Increased Criminal Behavior Increased Risk of Incarceration AA Decreased Criminal Behavior Average Risk of Incarceration aa *AA more common in blacks; aa more common in whites

  25. The Interaction of Genes and Social Forces Social Forces Genotype High Skin Melanin Increased Risk of Incarceration AA Low Skin Melanin Average Risk of Incarceration aa

  26. The Interaction of Genes and Social Forces Social Forces Genotype Increased Risk of Hypertension, Heart disease, Cancer, etc High Skin Melanin AA Average Risk of Hypertension, Heart disease, Cancer, etc Low Skin Melanin aa

  27. Genetics and Public Health “ (T)he real challenge for the NHGRI is to build bridges between its grantees and therapeutics. Notwithstanding biologists’ deep desire to understand the genome, their most immediate challenge is to make it relevant to public heath. The relevance will not be found by identifying genes associated with rare diseases . . but by (tackling) the common, complex diseases. Editorial, Nature Genetics, Feb., 2002

  28. Incorporating DNA Science into Public Health Germ Theory Antimicrobials X-rays Vaccination Biochemistry ? Molecular Genetics

  29. Potential Impact of Molecular Genetics on Medicine and Public Health • Prenatal screening / Diagnostic testing • Gene therapy • Define susceptibility to common disease • Drug discovery / Predicting drug response • Explain health disparities

  30. Incidence of β-Thalassemia in Sardinia, Greece and Cyprus, 1975 - 2000

  31. What is Race? Assumes structure in the genome- Variants at one locus are correlated with variants in other regions, creating distinct “packages” or correlated patterns among sub-populations. In non-human species requires Fst > 0.15. (Fst = proportion of variance within vs. between groups.)

  32. Questions about Race: • Based on population genetics, is continental race a valid category? • 2. Is continental race a useful category for biomedical research?

  33. In biomedicine, we want to know, Can race . . . • Be used to guide drug therapy? • 2. Help us understand the causes of disease? • 3. Categorize patients in terms of disease progression or pathophysiologic processes?

  34. Categorization of humans in biomedical research: genes, race and disease. Risch N, et al. Genome Biology 2002;3/7/comment 2007.1-2007.12 - Genetic studies have recapitulated the classical definition of races based on continental ancestry… - Genetic differentiation is greatest when defined on a continental basis… - If biological is defined by susceptibility to and natural history of a chronic disease, than numerous studies over past decades have documented biological differences among races…

  35. Race as a guide to drug therapy . . . Variation in Cytochrome P450 Gene Variants Populations [Allele Frequency (%)] GeneA B C D CYP1A2 34 31 40 41 CYP2C19 9 37 27 25 CYP2D6 53 39 70 30 Wilson et al, Nature Genetics 2001

  36. Race as a guide to drug therapy . . . Genetic variants that alter drug metabolism vary among populations . . . But virtually never in an all or-none-pattern. For race to be a surrogate for a variant, you need high (> 90%) sensitivity AND specificity. If you want to know whether a patient has a variant you have to test for it.

  37. Does cluster analysis reconstruct races?

  38. Estimated World Population Structure Based on 52 Populations (Rosenberg et al, Science, 2002)

  39. Does cluster analysis reconstruct races? • Conditional on: • number of samples • geographic distribution • type of markers – microsatellites vs. SNPs

  40. Does continental race summarize genetic variation of medical relevance?

  41. Distribution of Single Gene Disorders – Tay Sachs – mainly in persons of Jewish descent Cystic Fibrosis – northern Europeans Thalessemia – extends from Italy to Thailand Sickle cell – much of sub-Saharan Africa (but not South Africa), many Arab groups and across to India Distribution of Common Complex Disorders – World – wide, and common in all racial groups Eg, Hypertension – lifetime incidence risk ~ 80% in the US

  42. Does continental race summarize genetic variation of medical relevance? • rare diseases cluster in sub-populations, not race; common diseases do not cluster by race • continental race is not the population unit of interest • geographic variation within race is important • social/cultural heterogeneity within race is more important for common disease

  43. Types of Genetic Effects Likely to be Encountered Nature of the EffectFrequency of Occurrence Large, single gene Rare Moderate, a few genes Infrequent Small, many genes Ubiquitous

  44. Relationship Between the Impact of a Specific Genetic Polymorphism and Prevalence of the Related Disease Role of a Specific Genetic Variant Prevalence of Disease

  45. Competing Hypotheses for Genes and Common Disease Common Disease: Common Variants, or Common Disease: Many Rare Variants

  46. Haplotype Patterns and Exchanges in Three Chromosomal Blocks(The structure of haplotype blocks across the human genome, Gabriele et al, Science, in press.

  47. Comparison of Haplotype Blocks Across Population Samples Gabriel et al, Science 2002

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