Author + information
- Anthony N. DeMaria, MD, Editor-in-Chief, Journal of the American College of Cardiology⁎ ()
- ↵⁎Address correspondence to:
Dr. Anthony N. DeMaria, Editor-in-Chief, Journal of the American College of Cardiology, 3655 Nobel Drive, Suite 630, San Diego, California 92112
Recently, my attention was again drawn to the issue of the relevance and importance of racial and geographical designations in medicine and, in fact, in society in general. The San Diego community has come together for a joint effort to increase the percentage of patients receiving appropriate therapy for hypertension, hyperlipidemia, and other atherosclerotic risk factors. At a recent meeting, we were addressed by an African-American physician who stressed the importance of race and place in terms of achieving guideline-prescribed goals for these risk factors. His presentation prompted me to revisit the controversy of whether, independent of the socioeconomic and cultural variables, either of these characteristics, but particularly race, is of value in delineating propensity to disease or response to treatment.
As I delved into the literature, it soon became obvious that confusion existed in regard to several of the terms often used to classify patients, such as race, ethnicity, and ancestry. So, I went to the Merriam-Webster dictionary, where I found that the definition of race was “a family, tribe, people, or nation belonging to the same stock” (1). This designation is somewhat nonspecific, and has multiple cultural and genetic implications. In fact, the most common basis for racial designation that I have encountered is phenotype, such as skin color. Obviously, genetic classification should be more important. It seemed that genetic implications might be better conveyed by the term ethnicity, where ethnic is defined as “of or relating to large groups of people classed according to common racial, national, tribal, religious, linguistic, or cultural origin or background” (1). Since this still did not fully convey the genetic characteristics that would be important, it occurred to me that the term ancestry might be more relevant to medicine. The dictionary definition for ancestry is “line of descent or lineage” (1), and this term seems to best represent the important differences in groups of individuals that could influence their risk of disease or response to therapy. Nevertheless, race is the term that remains most commonly used in daily life.
Despite the confusion of these terms, the designation of race has come to occupy an important place in everyday medicine. Patients are typically described as African American, Asian, or Hispanic in histories and physicals. It is recognized that many monogenic diseases are more prevalent or nearly exclusively present in some racial/ethnic groups. A variable response to therapy has been described for racial groups, particularly in regard to hypertension and heart failure in African Americans. The implication is that racial classifications convey some underlying genetic/genomic uniqueness to a group of people that clearly distinguishes them from others. The extent to which such differences exist, and their clinical importance, remains a source of considerable debate, and the literature about this is more extensive than I had ever realized.
The relationship between race and ancestry can be quite variable (2). Genetic variance has been estimated by ancestry informative markers and expressed by a statistical metric called Wright's Fixation Index. Based upon these analyses, genetic variance between sub-Saharan Africans, Northern Europeans, and East Asians is only 5% to 15%. Data derived from several studies indicates that the West African contribution to the ancestry of individual African Americans ranges from 20% to 100%, with an average of 20% from non-West African sources. Similarly, approximately 30% of European Americans have been estimated to have more than 10% non-European ancestry. Accordingly, there is often a significant difference between race, usually categorized by phenotype and geography, and ancestry represented by genotype.
Some have argued that, despite the genetic imprecision of racial designation, race remains an important characteristic from a medical perspective (3). They point out that the over 85% of the genetic variance that exists is between individuals of a given race, and only 15% or so exist between races. They emphasize that the lack of interbreeding that resulted in the formation of human subgroups was largely due to geography. The proponents of the relevance of race emphasize that the risk of disease is due not only to genetics, but also to environment, and that race is a strong surrogate for the latter. From a practical standpoint, most Americans identify with a single race, and detailed genetic characterization would require sophisticated and expensive testing.
In contrast to the above, we have now entered the era of personalized medicine, and the focus has gone from populations to individuals. The ultimate goal now is to identify the genome of every individual so as to predict his or her risk of disease and response to therapy. The human genome has been sequenced, and genome-wide association studies have identified a number of alleles that convey risk or pharmacogenomic characteristics. Given the predominance of genetic variation within races rather than between races, it would be expected that the importance of race would be diminished. In any event, those genetic differences related to race would, of course, be delineated in the course of examining the individual genome.
It seems apparent that the definition of the specific genome is clearly the most scientifically accurate and medically valuable method to classify an individual. However, environmental factors clearly play an important role in determining a person's health. The socioeconomic and cultural variables that distinguish individuals are not infrequently of greater impact on their health than any genetic factors. In as much as race is often closely related to these environmental considerations, it is of some value in characterizing people. However, given the large percentage of genetic variability within individual races, the smaller genetic variability between races, and the substantial intermixing of the gene pool between races, the implications of phenotype are limited in their value to distinguish ancestry.
Given the above, one can reasonably ask if there is any reason to specify race as a subgroup in any study. Stated another way, does the color of someone's skin indicate much of substantial importance regarding his or her risk of disease or response to therapy? In most cases, the answer is likely to be no. If it does have significance, it is more likely to be related to environment than racial genetics. In medicine, as in life in general, the races are intrinsically much, much more like each other than they are different.
- American College of Cardiology Foundation