Schizophrenia is a common disease associated with reduced fertility. Therefore, the
existence of common susceptibility alleles not removed by natural selection may be
considered an evolutionary paradox. The antagonistic pleiotropy model, proposed to
explain this paradox, states that an allele may be common because of its overall selective
advantage, in spite of deleterious effects on specific traits. Recent work on DAOA,
PPP1R1B, and APOL1 suggests that these genes present common alleles associated to
increase risk of schizophrenia but conferring an overall selective advantage, related
to better cognitive performance (DAOA and PPP1R1B) or protection against pathogens
(APOL1). To test if these genes fit the antagonistic pleiotropy model, we searched
for recent natural selection at these loci applying the long-range haplotype test
on data from the HapMap Project; and performed case-control association analysis in
a well-powered sample, including 301 schizophrenic patients and 604 controls from
Spain. For DAOA and PPP1R1B, we genotyped the Single-nucleotide polymorphisms (SNPs)
needed to replicate previous associations, while for APOL1, we genotyped 15 tagSNPs,
and seven putative functional SNPs. We did not detect evidence of recent natural selection.
Furthermore, we did not find significant associations. Thus, these genes do not fit
the antagonistic pleiotropy model.