Impact of schizophrenia candidate genes on schizotypy and cognitive endophenotypes at the population level

BackgroundAspects of cognitive function and schizotypy have been proposed as potential endophenotypes for schizophrenia. It is unknown if the expression of these endophenotypes at the population level is modulated by the genetic variability of candidate susceptibility genes for schizophrenia.MethodsWe examined the potential impact of 19 single nucleotide polymorphisms (SNPs) within five susceptibility genes for schizophrenia (COMT, DTNP1, NRG1, DAOA/G32 and DAAO genes) on cognition and self-rated schizotypy, in a representative population of 2,243 young male military conscripts. Single SNP and haplotype associations were evaluated.ResultsVal carriers of the COMT val 158 met polymorphism, were associated with higher scores on the negative schizotypy factor, and a greater variability of response in attention capacity. DTNP1 SNPs rs2619522 and rs760761 exhibited several single marker associations, the minor alleles being associated with lower attention capacity but also a decrease in positive and paranoid schizotypy scores. DTNP1 haplotype load had borderline associations with non verbal IQ, paranoid schizotypy and sustained attention. For individual NRG1 polymorphisms, isolated but weak signals of association were noted with sustained attention and working memory, but not schizotypy. The risk allele of functional SNP8NRG243177 was associated with reduced spatial working memory capacity. An isolated effect of DAAO haplotype variability was noted on negative and disorganization schizotypy. No convincing association of DAOA/G32 variability was detected.ConclusionDTNP1 and val 158 met COMT, and less so NRG1 and DAAO variants, may exert gene-specific modulating effects on schizophrenia endophenotypes at the population level.