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Recent human evolution has shaped geographical differences in susceptibility to disease

Urko M Marigorta1, Oscar Lao2, Ferran Casals1, Francesc Calafell13, Carlos Morcillo-Suárez14, Rui Faria15, Elena Bosch13, François Serra6, Jaume Bertranpetit13, Hernán Dopazo6 and Arcadi Navarro147*

Author Affiliations

1 Institute of Evolutionary Biology (UPF-CSIC), PRBB, Doctor Aiguader 88, 08003, Barcelona, Catalonia, Spain

2 Department of Forensic Molecular Biology, Erasmus University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands

3 CIBER en Epidemiologia y Salud Pública (CIBERESP), Barcelona, Catalonia, Spain

4 National Institute for Bioinformatics, Universitat Pompeu Fabra, Barcelona, Spain

5 CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade de Porto, Campus Agrário de Vairão, 4485 - 661, Vairão, Portugal

6 Pharmacogenomics and Comparative Genomics Unit, Centro de Investigación Príncipe Felipe (CIPF), Valencia 46012, Spain

7 Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain

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BMC Genomics 2011, 12:55  doi:10.1186/1471-2164-12-55

Published: 24 January 2011



Searching for associations between genetic variants and complex diseases has been a very active area of research for over two decades. More than 51,000 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, many of the putative risk variants detected so far 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.


We report three main findings. 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 differences in replicability of disease associated-loci between Europeans and East Asians are 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.


Our 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.