Genetic Investigation of Race and Addiction

In their article “Association of Substance Use Disorders With Childhood Trauma but not African Genetic Heritage in an African American Cohort,” Ducci et al. raise a new perspective on racial differences that has not been previously applied to the consideration of the origins of mental illnesses and substance use (1) . Substance use has long been known to be increased in impoverished African American neighborhoods. This association is one of several that psychiatrists have identified in looking at the effect of race in mental illness. Another example is decreased response to treatment for depression, reported in the STAR*D study (2) . Racial stereotyping is anathema to psychiatrists, but differences in the prevalence and response to treatment of illnesses must be considered for understanding the causes of these illnesses and for designing optimal health care delivery systems.

Human beings arose as a species in Africa and lived there over 100,000 years before beginning their migration to other continents about 100,000 years ago (3) . Hence, African genomes contain most of the genetic diversity in the human population. People from Africa migrating to Europe and Asia in the past thousands of years became isolated from each other. Loss of some of the genetic diversity in each of these migrating populations and subsequent genetic mutations led to the small, but detectable, molecular differences that distinguish the world’s racial groups. Thus, all peoples of the world were originally part of the African population, but founders of each new race took only part of Africa’s genetic diversity to their new home.

The forced transport of Africans to America resulted in the reintroduction of the full genetic diversity of Africa into the Americas. As intermarriages occurred, there was a new mixture of genetic variants from Africa into the European and other groups. This admixture is still ongoing today. As part of the increased understanding of the molecular biology of the human genome, geneticists have identified a number of variants in different genes for which Africans and Europeans have diverged. Ducci et al. used genetic techniques that are now widely available in research laboratories to estimate for each individual in their study the proportion of their variants that were of African origin, compared to European origin.

Ducci et al. employed this genetic estimate to answer a nature versus nurture question about the effect of race on substance use. If Africans’ genetic backgrounds contain variants that increase their risk for substance use, then the estimate of the proportion of African variants should be correlated with the prevalence of substance use. This correlation was not found in the African American addicts whom they studied, which suggests that there is no racially based genetic reason for their increased substance use. Ducci et al. also examined associations of African genetic background with childhood trauma, which has been associated with substance use, and found a reverse correlation. African genetic background was associated with lower risk for childhood trauma. Finally, they investigated the association of African genetic background with census tract income level and found a modestly significant effect, with the African variants being associated with living in poorer neighborhoods, which is also a risk factor for substance use.

Thus, the race effect on substance use reported in epidemiological studies appears to be a very indirect one that reflects the lingering effects of the social history of the introduction of Africans into American society through enslavement. What is noteworthy is that the effect is very subtle. It persists even within a group that as a whole considers itself African American, with those addicts who are genetically more African living in poorer neighborhoods than those who are less African. It should be clarified that the article does not establish that living in a poorer neighborhood is more likely to cause addiction, because the genetic effect was assessed only within a group of addicts. Nor does it establish that living in a poorer neighborhood is associated with African genetic background for the entire population.

Readers might question whether it was reasonable to perform this study and to publish its results, because it could be viewed as simply addressing—and dismissing—a shibboleth about the effect of race on addiction. Substance use and abuse are highly heritable illnesses (4) . Indeed, some forms of substance abuse, like alcoholism, differ markedly between racial groups for genetic reasons. Therefore, racial differences might have been a hint about genetic predisposition that is worthy of investigation. The negative findings of Ducci et al. remind us through sophisticated molecular genetics that the presumption that all are created equal is the best starting hypothesis.