Genetics and Race Understanding The Genetic Basis of Common Disease and Human Traits

May 1, 2007

Vence L. Bonham, Jr., J.D.Senior Advisor to the Director on Societal Implications of GenomicsAssociate Investigator, Social and Behavioral Research Branch National Human Genome Research InstituteNational Institutes of Health Department of Health and Human Services

Understand the relationship between genomics, race and ethnicity, and the consequences of uncovering these relationshipsGrand Challenge III-3Collins FS et al. Nature, Vol. 422,no. 6934, April 24, 2003

RACE In America

Potential Questions to Ask about Studies focused on Genetics and Race:

What was the basis for choosing the population(s) to study? How did the study investigators categorize or define the study populations?Is the variation peculiar to a specific group (race or ethnicity) or only more common in it?What are potential causes of the differences in outcomes beyond genetics?What are the social implications of misinterpretation of the data?What is the medical significance of the variation? What does it mean for health and disease?

What was the basis for choosing the population to study?

How did the study categorize or define the study populations?

Historical Analysis Demonstrates That the United States Definitions of Race Have Been Fluid, Inconsistent, and Often Influenced by Political and Economic Factors

U.S. Census Definitions of Race1790 - Free (White or Other), Slave1860 - White, Black, Mulatto1890 - White, Black, Mulatto, Chinese, Indian, Quadroon, Octoroon, Japanese1900 - White, Black (of Negro Descent), Chinese, Indian, Japanese

OMB Directive 15 (1977)Four races:American Indian or Alaska NativeAsian or Pacific IslanderBlackWhiteThese classifications are neither scientific nor anthropological in nature.

Revised Race and EthnicityCategories - OMBDesignates Five Races:American Indian or Alaska NativeAsianBlack or African AmericanNative Hawaiian or Other Pacific IslanderWhiteNo Changes in EthnicityPersons May Identify More Than One Race

Black or AfricanAmericanWhite AsianNative Hawaiian or Other Pacific IslanderAmerican Indian or Alaska NativeHispanic/Latino

African AncestryNorthern EuropeanAncestryAsianAncestryPacific IslanderAncestryAmerican Indian AncestryHispanic/LatinoAncestry

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Can a specific ethnic group (e.g. HapMap population) be generalized to all individuals within a U.S. census category of people?

African origin of anatomically modern humansadapted from Hedges, 2000, Nature 408: 652-3

Most studies of genetic variation using many types of markers, show higher levels of genetic variation in African populations than in non-African populations.Tishkoff SA, Kidd KK. Implications of biogeography of human populations for race and medicineNature Genetics; 36 (11): S21- S27

Ancestry vs. RaceAfrican-AmericanAfrican-AmericanL. Jorde

Self Identified Race correlates with human genetic variation, but it is an imprecise correlation; ancestry is more informative

What are potential causes of the differences in outcomes beyond genetics?

Social Determinants of HealthSocioeconomic statusTransportation Housing Access to services EducationIncome and WealthDietDiscrimination by social grouping (e.g. race, gender, class)Social and environmental stressorsCDC/ATSDR Social Determinants of Health Working Group 2005

Population surveys in the US from early in the last century have consistently documented higher blood pressures and related cardiovascular sequelae in blacks compared to whites. The enormous attention focused on this observation has resulted in a dichotomous view of hypertension risk: whereby populations of African origin are considered more susceptible than all other continental groupings and a strong genetic hypothesis of inherent predisposition to hypertension among blacks has become the conventional wisdom.Richard Cooper et al. BMC Medicine 2005, 3:2

HypertensionRichard Cooper et al. BMC Medicine 2005, 3:2

These data demonstrate that not only is there a wide variation in hypertension prevalence among both racial groups, the rates among blacks are not unusually high when viewed internationally. These data suggest that the impact of environmental factors among both populations may have been under-appreciated.Richard Cooper et al. BMC Medicine 2005, 3:2

What are the implications of misinterpretation of the data?

Ebony Magazine, May 1966

The most significant feature of sickle cell anemia is the fact that it is apparently the only known disease that is completely confined to a single race

Annon, Sickle Cell Anemia: A Race Specific Disease. JAMA 1947; 133:33

Is the variation peculiar to a specific group (race or ethnicity) or only more common in it?

How is variation distributed within and between populations? Average difference between individuals within major populationsAverage difference between individuals between major populationsL. Jorde

What is the medical significance of the variation? What does it mean for health and disease?

Indications And UsageBiDil is indicated for the treatment of heart failure as an adjunct to standard therapy in self-identified black patients to improve survival to prolong time to hospitalization for heart failure, and to improve patient reported functional status.

What Do Doctors Think?

So, I think we clearly know that biologically there are different chemicals and different functional processes going on in an African American versus a white patient, you have to take that into account. Theyre going to respond better to one drug more than another perhaps (Detroit White Physician)Physicians Understanding of Human Genetic Variation Study

Race is a social construct. Its useful, given the historic context; I would not let anybody, not refer to me as a Black woman. However, I actually do believe that theres no biological basis for that. And, science proves me out. (Atlanta Black Physician)Physicians Understanding of Human Genetic Variation Study

In biology a new world is expanding in front of our eyes may we learn to use it wisely

Francis Crick, April 2003 Closing Thoughts