title: Analysis of ProDH, COMT and ZDHHC8 risk variants does not support individual or interactive effects on schizophrenia susceptibility.
abstract: Synergistic interaction between genes on chromosome 22q11 recently has been proposed as a possible mechanism which could confer increased risk for schizophrenia. Based on this hypothesis, our study aimed to explore main, cis- and trans-interacting effects of three candidate genes on 22q11, ProDH, COMT and ZDHHC8. We selected four putative risk variants, residing within these genes, ProDH 1945, ProDH 2026, COMT ValMet and ZDHHC8 rs175174, and studied these in a large family-based schizophrenia association sample of European origin (488 Bulgarian parent-offspring trios). The presence of interaction between the variants was tested by conditional logistic regression analysis based on a case-pseudocontrol design. Our study did not find statistical evidence for allelic (investigation of ProDH markers only), genotypic, haplotypic, or interactive effects between ProDH, COMT and ZDHHC8. Our data do not support the hypothesis that an interaction between these genes influences susceptibility to schizophrenia.
authors.affiliation: Department of Psychological Medicine, Cardiff University, Heath Park, Cardiff, UK, and Department of Psychiatry, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
authors.forename: Beate
authors.initials: B
authors.lastname: Glaser
authors.forename: Valentina
authors.initials: V
authors.lastname: Moskvina
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Kieran C
authors.initials: KC
authors.lastname: Murphy
authors.forename: Hywel
authors.initials: H
authors.lastname: Williams
authors.forename: Nigel
authors.initials: N
authors.lastname: Williams
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
mesh_terms: D000217:Acyltransferases / Q000235:genetics*; D000328:Adult; D002031:Bulgaria; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D011394:Proline Oxidase / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D000217:Acyltransferases; D002394:Catechol O-Methyltransferase; D005819:Genetic Markers; D008565:Membrane Proteins; D011394:Proline Oxidase; D050826:Suppressor of Cytokine Signaling Proteins; C488097:ZDHHC8 protein, human