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


RESULTS
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.


CONCLUSIONS
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.
Institute of Evolutionary Biology (UPF-CSIC), PRBB, Doctor Aiguader 88, 08003, Barcelona, Catalonia, Spain.
Urko M
UM
Marigorta
Oscar
O
Lao
Ferran
F
Casals
Francesc
F
Calafell
Carlos
C
Morcillo-Suárez
Rui
R
Faria
Elena
E
Bosch
François
F
Serra
Jaume
J
Bertranpetit
Hernán
H
Dopazo
Arcadi
A
Navarro
D044466:Asian People; D005075:Biological Evolution; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D044465:White People
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