Is Genomics the Cure for Disparities? Francis S. Collins, M.D., Ph.D. National Leadership Summit to Eliminate Racial and Ethnic Disparities in Health January 10, 2006

What is the nature of human genetic variation?

Genetic Variation in Africa

Spreading around the World

What is the relationship between genetic variation and race?

December 18, 2002 Genes expose race only as a sham The idea of race was not reflected in a person’s genes, Brazilian researchers said yesterday, confirming what scientists have long said – that race has no meaning genetically.

June 4, 2003 No trace of race; Genome Sequencing Project proves nothing biological separates peoples

October 1, 2002 For Sale: A DNA Test To Measure Racial Mix A company in Sarasota, Fla., is offering a DNA test that it says will measure customers’ racial ancestry and their ancestral proportions if they are of a mixed race.

July 28, 2003 Race Plays Role in New Drug Trials; Treatment by Genetic Origin, Ethnicity Divides Medical Profession

What does “race” mean anyway?

What we know about genetics and race We are all 99.9% identical at the DNA level That still leaves millions of differences Most of these variants were present in our common ancestors But the frequency of a particular variant will often differ between populations, as a result of –“Genetic drift” –Founder effects –Selection –New mutations

What we know about genetics and race (cont.) Such differences may be used to make statistical predictions of geographic origins, but in general there will be considerable overlap between groups The history of human populations is more of a trellis than a tree

© 1999 Kenneth K Kidd, Yale University The “Wisteria Vine’ view of human evolution and diversification AfricaOut of Africa

What we know about genetics and race (cont.) Except in cases of extreme geographic isolation, the genetic boundaries around population groups will be blurry and imprecise When differences in prevalence of illness are observed between groups, this could be due to: –Genetic differences –Dietary, cultural, environmental, socioeconomic factors –A mixture of both

SELF-IDENTIFIED RACE OR ETHNICITY ENVIRONMENTAL EXPOSURESENVIRONMENTAL EXPOSURES ANCENTRALGEOGRAPHICORIGINSANCENTRALGEOGRAPHICORIGINS VARIANTS IN DISEASEGENESVARIANTS IN DISEASEGENES EDUCATION ACCESS TO HEALTH CARE CULTURE STRESS SOCIOECONOMIC STATUS GENOME VARIATION HEALTH OR DISEASE

The Case of BiDil ® BiDil ® is a combination of two generic drugs, isosorbide dinitrate and hydralazine. It acts as a nitric oxide enhancer. Nitric oxide dilates blood vessels, reducing the amount of resistance the heart has to pump against.

The Case of BiDil ® (cont.) BiDil ® was originally tested in clinical trials for heart failure in the 1980s and 1990s. It showed possible benefit, but the FDA ruled in 1997 that the results were unconvincing. A retrospective analysis suggested that benefit was greatest in African American patients. Patent was filed on the use of this drug for African Americans, and PTO approved it.

The Case of BiDil ® (cont.) BiDil ® was then tested for benefits in treating heart failure in 1100 African American men and women Trial was supported by the Association of Black Cardiologists and the National Medical Association

Survival Curve NEJM 351: , 2004

The Case of BiDil ® (cont.) FDA approved BiDil ® for the treatment of congestive heart failure in the summer of 2005 Indications: “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.” A mixed blessing?

Summary “Race” is a term which carries a great deal of baggage; the use of more precise definitions would assist our societal dialogue Much is being learned about worldwide genetic variation that informs us of our shared heritage Neither of these statements is correct: –Race has absolutely no biological basis –Genetics allows us to draw sharp boundaries between groups To understand and prevent health disparities, we should seek more proximate causes, not depend on the muddy proxies of race and ethnicity

Is Genomics the Cure for Disparities? Probably not But in some instances, genomics may identify heritable factors that play a role, though almost always in concert with environmental factors We need more data