Friday, July 05, 2002

Need I say more? This article at Genome Biology: "Categorization of humans in biomedical research: genes, race and disease" has a nice little review of why it's important to consider race in medical research. (And no, I'm not one of the authors.) Here's the abstract - full access requires a subscription.

A debate has arisen regarding the validity of racial/ethnic categories for biomedical and genetic research. Some claim 'no biological basis for race' while others advocate a 'race-neutral' approach, using genetic clustering rather than self-identified ethnicity for human genetic categorization. We provide an epidemiologic perspective on the issue of human categorization in biomedical and genetic research that strongly supports the continued use of self-identified race and ethnicity.

Update: Note that you can register for a free trial in order to view the article. It's quite an excellent site - I think that it will be considered a good journal in a few years time, especially considering the heavyweights on the editorial board. Here are some nice clips:
A major discussion has arisen recently regarding optimal strategies for categorizing humans, especially in the United States, for the purpose of biomedical research, both etiologic and pharmaceutical. Clearly it is important to know whether particular individuals within the population are more susceptible to particular diseases or most likely to benefit from certain therapeutic interventions. The focus of the dialogue has been the relative merit of the concept of 'race' or 'ethnicity', especially from the genetic perspective. For example, a recent editorial in the New England Journal of Medicine [1] claimed that "race is biologically meaningless" and warned that "instruction in medical genetics should emphasize the fallacy of race as a scientific concept and the dangers inherent in practicing race-based medicine." In support of this perspective, a recent article in Nature Genetics [2] purported to find that "commonly used ethnic labels are both insufficient and inaccurate representations of inferred genetic clusters." Furthermore, a supporting editorial in the same issue [3] concluded that "population clusters identified by genotype analysis seem to be more informative than those identified by skin color or self-declaration of 'race'." These conclusions seem consistent with the claim that "there is no biological basis for 'race'" [3] and that "the myth of major genetic differences across 'races' is nonetheless worth dismissing with genetic evidence" [4]. Of course, the use of the term "major" leaves the door open for possible differences but a priori limits any potential significance of such differences. In our view, much of this discussion does not derive from an objective scientific perspective. This is understandable, given both historic and current inequities based on perceived racial or ethnic identities, both in the US and around the world, and the resulting sensitivities in such debates. Nonetheless, we demonstrate here that from both an objective and scientific (genetic and epidemiologic) perspective there is great validity in racial/ethnic self-categorizations, both from the research and public policy points of view. ... Probably the best way to examine the issue of genetic subgrouping is through the lens of human evolution. If the human population mated at random, there would be no issue of genetic subgrouping because the chance of any individual carrying a specific gene variant would be evenly distributed around the world. For a variety of reasons, however, including geography, sociology and culture, humans have not and do not currently mate randomly, either on a global level or within countries such as the US. A clearer picture of human evolution has emerged from numerous studies over the past decade using a variety of genetic markers and involving indigenous populations from around the world. In summary, populations outside Africa derive from one or more migration events out of Africa within the last 100,000 years [5,6,7,8,9,10,11]. The greatest genetic variation occurs within Africans, with variation outside Africa representing either a subset of African diversity or newly arisen variants. Genetic differentiation between individuals depends on the degree and duration of separation of their ancestors. Geographic isolation and in-breeding (endogamy) due to social and/or cultural forces over extended time periods create and enhance genetic differentiation, while migration and inter-mating reduce it. With this as background, it is not surprising that numerous human population genetic studies have come to the identical conclusion - that genetic differentiation is greatest when defined on a continental basis. The results are the same irrespective of the type of genetic markers employed, be they classical systems [5], restriction fragment length polymorphisms (RFLPs) [6], microsatellites [7,8,9,10,11], or single nucleotide polymorphisms (SNPs) [12]. For example, studying 14 indigenous populations from 5 continents with 30 microsatellite loci, Bowcock et al. [7] observed that the 14 populations clustered into the five continental groups, as depicted in Figure 1. The African branch included three sub-Saharan populations, CAR pygmies, Zaire pygmies, and the Lisongo; the Caucasian branch included Northern Europeans and Northern Italians; the Pacific Islander branch included Melanesians, New Guineans and Australians; the East Asian branch included Chinese, Japanese and Cambodians; and the Native American branch included Mayans from Mexico and the Surui and Karitiana from the Amazon basin. The identical diagram has since been derived by others, using a similar or greater number of microsatellite markers and individuals [8,9]. More recently, a survey of 3,899 SNPs in 313 genes based on US populations (Caucasians, African-Americans, Asians and Hispanics) once again provided distinct and non-overlapping clustering of the Caucasian, African-American and Asian samples [12]: "The results confirmed the integrity of the self-described ancestry of these individuals". Hispanics, who represent a recently admixed group between Native American, Caucasian and African, did not form a distinct subgroup, but clustered variously with the other groups. A previous cluster analysis based on a much smaller number of SNPs led to a similar conclusion: "A tree relating 144 individuals from 12 human groups of Africa, Asia, Europe and Oceania, inferred from an average of 75 DNA polymorphisms/individual, is remarkable in that most individuals cluster with other members of their regional group" [13]. Effectively, these population genetic studies have recapitulated the classical definition of races based on continental ancestry - namely African, Caucasian (Europe and Middle East), Asian, Pacific Islander (for example, Australian, New Guinean and Melanesian), and Native American. ... Two arguments against racial categorization as defined above are firstly that race has no biological basis [1,3], and secondly that there are racial differences but they are merely cosmetic, reflecting superficial characteristics such as skin color and facial features that involve a very small number of genetic loci that were selected historically; these superficial differences do not reflect any additional genetic distinctiveness [2]. A response to the first of these points depends on the definition of 'biological'. If biological is defined as genetic then, as detailed above, a decade or more of population genetics research has documented genetic, and therefore biological, differentiation among the races. This conclusion was most recently reinforced by the analysis of Wilson et al. [2]. If biological is defined by susceptibility to, and natural history of, a chronic disease, then again numerous studies over past decades have documented biological differences among the races. In this context, it is difficult to imagine that such differences are not meaningful. Indeed, it is difficult to conceive of a definition of 'biological' that does not lead to racial differentiation, except perhaps one as extreme as speciation. A forceful presentation of the second point - that racial differences are merely cosmetic - was given recently in an editorial in the New England Journal of Medicine [1]: "Such research mistakenly assumes an inherent biological difference between black-skinned and white-skinned people. It falls into error by attributing a complex physiological or clinical phenomenon to arbitrary aspects of external appearance. It is implausible that the few genes that account for such outward characteristics could be meaningfully linked to multigenic diseases such as diabetes mellitus or to the intricacies of the therapeutic effect of a drug." The logical flaw in this argument is the assumption that the blacks and whites in the referenced study differ only in skin pigment. Racial categorizations have never been based on skin pigment, but on indigenous continent of origin. For example, none of the population genetic studies cited above, including the study of Wilson et al. [2], used skin pigment of the study subjects, or genetic loci related to skin pigment, as predictive variables. Yet the various racial groups were easily distinguishable on the basis of even a modest number of random genetic markers; furthermore, categorization is extremely resistant to variation according to the type of markers used (for example, RFLPs, microsatellites or SNPs). Genetic differentiation among the races has also led to some variation in pigmentation across races, but considerable variation within races remains, and there is substantial overlap for this feature. For example, it would be difficult to distinguish most Caucasians and Asians on the basis of skin pigment alone, yet they are easily distinguished by genetic markers. The author of the above statement [1] is in error to assume that the only genetic differences between races, which may differ on average in pigmentation, are for the genes that determine pigmentation.

posted by godlesscapitalist | 7/05/2002 04:07:00 PM | |