title: Fine mapping on chromosome 13q32-34 and brain expression analysis implicates MYO16 in schizophrenia.
abstract: We previously reported linkage of schizophrenia and schizoaffective disorder to 13q32-34 in the European descent Afrikaner population from South Africa. The nature of genetic variation underlying linkage peaks in psychiatric disorders remains largely unknown and both rare and common variants may be contributing. Here, we examine the contribution of common variants located under the 13q32-34 linkage region. We used densely spaced SNPs to fine map the linkage peak region using both a discovery sample of 415 families and a meta-analysis incorporating two additional replication family samples. In a second phase of the study, we use one family-based data set with 237 families and independent case-control data sets for fine mapping of the common variant association signal using HapMap SNPs. We report a significant association with a genetic variant (rs9583277) within the gene encoding for the myosin heavy-chain Myr 8 (MYO16), which has been implicated in neuronal phosphoinositide 3-kinase signaling. Follow-up analysis of HapMap variation within MYO16 in a second set of Afrikaner families and additional case-control data sets of European descent highlighted a region across introns 2-6 as the most likely region to harbor common MYO16 risk variants. Expression analysis revealed a significant increase in the level of MYO16 expression in the brains of schizophrenia patients. Our results suggest that common variation within MYO16 may contribute to the genetic liability to schizophrenia.
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Rodriguez-Murillo
authors.affiliation: 1] Department of Psychiatry, Columbia University, New York, NY, USA [2] Department of Physiology, Columbia University, New York, NY, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Psychiatry and Weskoppies Hospital, University of Pretoria, Pretoria, South Africa.
authors.forename: J Louw
authors.initials: JL
authors.lastname: Roos
authors.affiliation: Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
authors.affiliation: 1] Department of Physiology, Columbia University, New York, NY, USA [2] Department of Neuroscience, Columbia University, New York, NY, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Gogos
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Karayiorgou
mesh_terms: D001921:Brain / Q000473:pathology*; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D018995:Myosin Heavy Chains / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D013019:South Africa; D044465:White People
chemical_list: C483469:MYH16 protein, human; C000606501:MYO16 protein, human; D018995:Myosin Heavy Chains