Ethnic differences and health disparities
Health disparities are differences in health status (such as incidence, prevalence, and mortality rates) between population groups. Health disparities depend on many factors, including age, gender, income, geography, ethnicity, and race. Overwhelmingly, disparities in health are the result of socio-political structures that drive some members of a society towards poorer health. Some have expressed concern that this gradient will be exacerbated if genetics draws attention and resources away from more important determinants of disparities . Furthermore, because disparities can occur along ethnic and racial lines (at least in the US), genetic explanation may reinforce racial stereotypes, a known contributor to disparities. We recognize these pitfalls, but given the central role of DNA in disease etiology and variable drug response, the potential of genetics and genomics to shed light on health disparities must be considered.
High-throughput genomics has illuminated the relationship between ethnicity and disease disparities. Although most genetic variation is shared among all human populations, a disease susceptibility locus can differ in frequency across populations. To illustrate, African Americans typically trace ancestry to western Africa and Europe; this type of population of mixed ancestry is called admixed. In chromosomal segments containing disease susceptibility loci, there will be excess ancestry in an admixed population from the ancestral populations with higher frequencies of risk alleles. Admixture mapping became feasible in 2004 and has generated some notable successes. For example, the incidence of end-stage renal disease (ESRD) is four times higher in African Americans than in European Americans. The hypothesis that susceptibility alleles for ESRD have higher frequencies in West African than European gene pools led to the identification of the Apolipoprotein L1 gene (APOL1) as a major effect gene . Interestingly, the frequency of the APOL1 risk variant (rs73885319) varies worldwide, ranging from 40% among the Yoruba from Nigeria to 20% in African Americans and 0% in Europeans and East Asians. This kidney disease risk variant is believed to have risen to high frequency in Africa because it confers resistance to trypanosomal infection and protects against the lethal form of African sleeping sickness.
Another example is differences in white blood cell (WBC) count, which have possible implications for disparity in cancer treatment and survival. Populations with African ancestry have lower WBC count than Europeans, and it has been suggested that lower WBC counts in African American women with early-stage breast cancer may lead to delays in treatment compared with European American women at a similar disease stage . Approximately 20% of variation in peripheral WBC counts between African Americans and European Americans can be explained by the promoter-null variant rs2814778 in the Duffy blood group gene DARC . The derived allele C is fixed between West Africans (frequency 100%) and Europeans and East Asians (frequency 0%); lack of genotypic variation within ancestral groups precludes detection via traditional genome-wide association studies.
Given such examples, methods that explicitly incorporate ancestrally specific effect sizes and differences in allele frequencies and linkage disequilibrium are being developed to empower studies of replication and better localization of disease risk variants across ancestral backgrounds. Furthermore, methodological advances now allow integration of admixture mapping and genotypic association, combining the power of the former with the resolution of the latter . We anticipate that such techniques will help elucidate the genetic component of health disparities.