We did not find enrichment for any measure of positive selection or Neanderthal introgression. A recent study explained a negative correlation between schizophrenia associations and metrics indicative of a Neanderthal selective sweep as evidence for positive selection or polygenic adaptation in schizophrenia12. We do not find any significant correlation in our model, which addresses the contribution of BGS, and hence our results are not consistent with large contributions of positive selection to the genetic architecture of schizophrenia (Table 1). Indeed, positive selection is not widespread in humans, as reported by other studies that explicitly considered or accounted for BGS28,51. Polygenic adaptation, the co-occurrence of many subtle allele frequency shifts at loci influencing complex traits52, remains an intriguing possibility but has not been implicated in psychiatric phenotypes, including schizophrenia, in recent analyses53,54. In contrast, BGS has been proposed as a mechanism driving human-Neanderthal incompatibilities, as regions with stronger estimated BGS have lower estimated Neanderthal introgression55. We therefore conclude that the bulk of the BGS signal we obtain is unlikely to be influenced by positive selection29, challenging theories of the selective advantage of schizophrenia risk alleles to explain the high population frequencies of these alleles.
