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 Genomics Associate Investigator, Social and Behavioral Research Branch National Human Genome Research Institute National Institutes of Health Department of Health and Human Services

“Understand the relationship between genomics, race and ethnicity, and the consequences of uncovering these relationships” Grand Challenge III-3 Collins 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 Race Free (White or Other), Slave White, Black, Mulatto White, Black, Mulatto, Chinese, Indian, Quadroon, Octoroon, Japanese White, Black (of Negro Descent), Chinese, Indian, Japanese

OMB Directive 15 (1977) Four races:American Indian or Alaska Native Asian or Pacific Islander Black White Two Ethnic Groups: Hispanic Origin Not of Hispanic Origin These classifications are “neither scientific nor anthropological in nature.”

Revised Race and Ethnicity Categories - OMB Designates Five Races: American Indian or Alaska Native Asian Black or African American Native Hawaiian or Other Pacific Islander White No Changes in Ethnicity Persons May Identify More Than One Race

Black or African American WhiteAsian Native Hawaiian or Other Pacific Islander American Indian or Alaska Native Hispanic/Latino

African Ancestry Northern European Ancestry Asian Ancestry Pacific Islander Ancestry American Indian Ancestry Hispanic/Latino Ancestry

? ? ? ? ? ?

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 humans adapted 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 medicine Nature Genetics; 36 (11): S21- S27

Ancestry vs. Race “African-American” L. 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 Health Socioeconomic status Transportation Housing Access to services Education Income and Wealth Diet Discrimination by social grouping (e.g. race, gender, class) Social and environmental stressors CDC/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

Hypertension Richard 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 populations Average difference between individuals between major populations L. Jorde

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

Indications And Usage “BiDil 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. They’re 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. It’s useful, given the historic context; I would not let anybody, not refer to me as a Black woman. However, I actually do believe that there’s 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