Recent human evolution has shaped geographical differences in susceptibility to disease.

MARIGORTA U.; O. LAO; F. CASALS; F. CALAFELL; C. MORCILLO-SUÁREZ; R. FARIA; E. BOSCH; F. SERRA; J. BERTRANPETIT; H. DOPAZO; A. NAVARRO

BMC GENOMICS

BIOMED CENTRAL LTD

Año: 2011 vol. 12 p. 55 - 65

1471-2164

Background Associations between genetic variants and complex diseases have been a very active area of research for over two decades. Up to now, more than 46,000 potential associations have been studied and published, a figure that keeps increasing, especially with the recent explosion of array-based Genome-Wide Association Studies. Even if the number of true associations described so far is high, a large number of the putative risk variants detected have failed to be consistently replicated and are widely considered false positives. Here, we focus on the world-wide patterns of replicability of published association studies. Results We report three main results. First, contrary to previous results, genes associated to complex diseases present lower degrees of genetic differentiation among human populations than average genome-wide levels. Second, also contrary to previous results, the replicability of disease associated-loci through different populations is highly correlated with genetic differentiation between these populations. Finally, highly replicated genes present increased levels of high-frequency derived alleles in European and Asian populations when compared to African populations. Conclusions These findings highlight the heterogeneous nature of the genetic etiology of complex disease, confirm the importance of the recent evolutionary history of our species in current patterns of disease susceptibility and could cast doubts on the status as false positives of some associations that have failed to replicate across populations.