BACKGROUND: Aspects of cognitive function and schizotypy have been proposed as potential endophenotypes for schizophrenia. It is unknown whether the expression of these endophenotypes at the population level is modulated by the genetic variability of candidate susceptibility genes for schizophrenia. METHODS: We examined the potential impact of 18 single nucleotide polymorphisms (SNPs) within the DTNBP1, NRG1, DAOA/G32, and DAAO genes, on cognition and self-rated schizotypy, in a representative population of 2243 young male military conscripts. Single SNP and haplotype associations were evaluated. RESULTS: The DTNBP1 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. The DTNBP1 haplotype load had borderline associations with nonverbal 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. CONCLUSIONS: The DTNBP1 and, less so, NRG1 and DAAO variants might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level.
BACKGROUND: Aspects of cognitive function and schizotypy have been proposed as potential endophenotypes for schizophrenia. It is unknown whether the expression of these endophenotypes at the population level is modulated by the genetic variability of candidate susceptibility genes for schizophrenia. METHODS: We examined the potential impact of 18 single nucleotide polymorphisms (SNPs) within the DTNBP1, NRG1, DAOA/G32, and DAAO genes, on cognition and self-rated schizotypy, in a representative population of 2243 young male military conscripts. Single SNP and haplotype associations were evaluated. RESULTS: The DTNBP1 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. The DTNBP1 haplotype load had borderline associations with nonverbal 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. CONCLUSIONS: The DTNBP1 and, less so, NRG1 and DAAO variants might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level.
Authors: Ehud Karavani; Or Zuk; Danny Zeevi; Nir Barzilai; Nikos C Stefanis; Alex Hatzimanolis; Nikolaos Smyrnis; Dimitrios Avramopoulos; Leonid Kruglyak; Gil Atzmon; Max Lam; Todd Lencz; Shai Carmi Journal: Cell Date: 2019-11-21 Impact factor: 41.582
Authors: Tiffany A Greenwood; Laura C Lazzeroni; Sarah S Murray; Kristin S Cadenhead; Monica E Calkins; Dorcas J Dobie; Michael F Green; Raquel E Gur; Ruben C Gur; Gary Hardiman; John R Kelsoe; Sherry Leonard; Gregory A Light; Keith H Nuechterlein; Ann Olincy; Allen D Radant; Nicholas J Schork; Larry J Seidman; Larry J Siever; Jeremy M Silverman; William S Stone; Neal R Swerdlow; Debby W Tsuang; Ming T Tsuang; Bruce I Turetsky; Robert Freedman; David L Braff Journal: Am J Psychiatry Date: 2011-04-15 Impact factor: 18.112
Authors: Markus Thimm; Axel Krug; Thilo Kellermann; Valentin Markov; Sören Krach; Andreas Jansen; Klaus Zerres; Thomas Eggermann; Tony Stöcker; N Jon Shah; Markus M Nöthen; Marcella Rietschel; Tilo Kircher Journal: Behav Brain Funct Date: 2010-09-16 Impact factor: 3.759