Box 2 The African-American multiple sclerosis admixture mapping study

MS was an ideal disease in which to test the proof of concept for admixture mapping (Reich et al. 2005). It is a complex disorder with strong evidence of heritable components. However before the African-American admixture mapping project, several decades of concerted research efforts had not revealed new risk loci. Most importantly with respect to admixture mapping, MS has a markedly different population prevalence, being extremely rare in sub-Saharan African groups and predominant in populations of Northern European descent. In the US, African-Americans, have a half to a third the relative risk of developing MS as do European Americans (Wallin et al. 2004). Based on this well-characterized epidemiology, and the fact that African-Americans are of mixed European and West African ancestry, the hypothesis of the MS admixture study was that genetic risk factors in African-Americans with MS should be of higher frequency in genomic regions inherited from their European ancestors. Thus, to localize these risk factors, admixture mapping scans through the entire genome of African-Americans with MS searching for regions where the proportion of European ancestry is higher than average.

To actualize the MS project (Reich et al. 2005), researchers at the Harvard/MIT ‘s Broad Institute who conceived the admixture study, partnered with the MS Genetics Group at the University of California at San Francisco (see: http://www.neurology.ucsf.edu/msdb/). This group had been gathering self-identified African-American MS cases and controls for some years. The admixture mapping study produced encouraging results—it identified a novel MS risk locus, which was indeed associated with a local increase in European ancestry. Researchers are now fine-mapping the locus to pinpoint the genetic variant(s) responsible for the admixture signal, and it is hoped, to identify a disease-associated gene, novel molecular mechanisms, and ultimately, a druggable target for therapeutic intervention.