title: Confirmation of the genetic association between the U2AF homology motif (UHM) kinase 1 (UHMK1) gene and schizophrenia on chromosome 1q23.3.
abstract: UHMK1 has previously been implicated as a susceptibility gene for schizophrenia in the 1q23.3 region by significant evidence of allelic and haplotypic association between schizophrenia and several genetic markers at UHMK1 in a London-based case-control sample. Further fine mapping of the UHMK1 gene locus in the University College London schizophrenia case-control sample was carried out with tagging SNPs. Two additional SNPs were found to be associated with schizophrenia (rs6604863 P = 0.02, rs10753578 P = 0.017). Tests of allelic and haplotypic association were then carried out in a second independent sample from Aberdeen consisting of 858 individuals with schizophrenia and 591 controls. Two of these SNPs also showed association in the Aberdeen sample (rs7513662 P = 0.0087, rs10753578 P = 0.022) and several haplotypes were associated (global permutation P = 0.0004). When the UCL and Aberdeen samples were combined three SNPs (rs7513662 P = 0.0007, rs6427680 P = 0.0252, rs6694863 P = 0.015) and several haplotypes showed association (eg HAP-A, HAP-B, HAP-C permutation P = 0.00005). The finding of allelic association with markers in the UHMK1 gene might help explain why it has not been possible, despite great effort, to satisfactorily confirm previously reported associations between schizophrenia and the genes RGS4 and NOS1AP/CAPON. These genes flank UHMK1 and all three loci are within a 700 kb region showing linkage to schizophrenia. The confirmation of association between UHMK1 and schizophrenia, rather than RGS4 and NOS1AP in the London sample, points to the possibility that previous efforts to accurately fine map a gene in the 1q23.3 region have lacked accuracy or may have suffered from methodological flaws.
authors.affiliation: Molecular Psychiatry Laboratory, Department of Mental Health Sciences, University College London Medical School, Windeyer Institute of Medical Sciences, London, UK.
authors.forename: Vinay
authors.initials: V
authors.lastname: Puri
authors.forename: Andrew
authors.initials: A
authors.lastname: McQuillin
authors.forename: Susmita
authors.initials: S
authors.lastname: Datta
authors.forename: Khalid
authors.initials: K
authors.lastname: Choudhury
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pimm
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Thirumalai
authors.forename: Robert
authors.initials: R
authors.lastname: Krasucki
authors.forename: Jacob
authors.initials: J
authors.lastname: Lawrence
authors.forename: Digby
authors.initials: D
authors.lastname: Quested
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bass
authors.forename: Caroline
authors.initials: C
authors.lastname: Crombie
authors.forename: Gillian
authors.initials: G
authors.lastname: Fraser
authors.forename: Nicholas
authors.initials: N
authors.lastname: Walker
authors.forename: Helen
authors.initials: H
authors.lastname: Moorey
authors.forename: Manaan Kar
authors.initials: MK
authors.lastname: Ray
authors.forename: Akeem
authors.initials: A
authors.lastname: Sule
authors.forename: David
authors.initials: D
authors.lastname: Curtis
authors.forename: David
authors.initials: D
authors.lastname: St Clair
authors.forename: Hugh
authors.initials: H
authors.lastname: Gurling
mesh_terms: D000328:Adult; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C530658:UHMK1 protein, human