FOXP2 gene and language impairment in schizophrenia: association and epigenetic studies

Twenty-seven SNPs of FOXP2 were genotyped in a cohort of 293 patients with schizophrenia and 340 controls. We analyzed in particular the association with the poverty of speech and the intensity of auditory hallucinations. Potential expansion of three trinucleotide repeats of FOXP2 was also screened in a subsample. Methylation analysis of a CpG island, located in the first exon of the gene, was performed in post-mortem brain samples, as well as qRT-PCR analysis.A significant association was found between the SNP rs2253478 and the item Poverty of speech of the Manchester scale (p = 0.038 after Bonferroni correction). In patients, we detected higher degree of methylation in the left parahippocampus gyrus than in the right one.FOXP2 might be involved in the language disorder in patients with schizophrenia. Epigenetic factors might be also implicated in the developing of this disorder.It is widely accepted that neutral drift and Darwinian positive selection have played an important role in the evolution of human features. During the last few years, research has been focused on human genome-wide scans of adaptative evolving loci to search for specific modern characteristics in this species [1]. Although most of them are related to fitness, it has been reported that some genes under positive selection in the human lineage can also confer vulnerability to some diseases [2-4].Schizophrenia, which is considered as a disease related to the origin of Homo sapiens, could be a by-product of an adaptative process [3,5,6]. Previous reports have indicated a relationship between positively selected genes and schizophrenia. Crespi et al. [3] found signals of positive selection in 28 of 76 schizophrenia candidate genes that had been previously reported as positive results in association studies. Evidence of recent positive selection in the human lineage has also been found in haplotypes of MAOB and GABRB2 genes, which also confer an increased risk to schizophrenia [2,4]. Furthermore, b