title: The Epsin 4 gene on chromosome 5q, which encodes the clathrin-associated protein enthoprotin, is involved in the genetic susceptibility to schizophrenia.
abstract: Chromosome 5q33 is a region that has previously shown good evidence of linkage to schizophrenia, with four LOD scores >3.00 in independent linkage studies. We studied 450 unrelated white English, Irish, Welsh, and Scottish research subjects with schizophrenia and 450 ancestrally matched supernormal controls. Four adjacent markers at the 5' end of the Epsin 4 gene showed significant evidence of linkage disequilibrium with schizophrenia. These included two microsatellite markers, D5S1403 (P=.01) and AAAT11 (P=.009), and two single-nucleotide-polymorphism markers within the Epsin 4 gene, rs10046055 (P=.007) and rs254664 (P=.01). A series of different two- and three-marker haplotypes were also significantly associated with schizophrenia, as confirmed with a permutation test (HapA, P=.004; HapB, P=.0005; HapC, P=.007; and HapD, P=.01). The Epsin 4 gene encodes the clathrin-associated protein enthoprotin, which has a role in transport and stability of neurotransmitter vesicles at the synapses and within neurons. A genetically determined abnormality in the structure, function, or expression of enthoprotin is likely to be responsible for genetic susceptibility to a subtype of schizophrenia on chromosome 5q33.3.
authors.affiliation: Molecular Psychiatry Laboratory, Department of Mental Health Sciences, University College London Medical School, Windeyer Institute of Medical Sciences, London, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pimm
authors.forename: Andrew
authors.initials: A
authors.lastname: McQuillin
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Thirumalai
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: Graham
authors.initials: G
authors.lastname: Lamb
authors.forename: Helen
authors.initials: H
authors.lastname: Moorey
authors.forename: Susmita R
authors.initials: SR
authors.lastname: Datta
authors.forename: Gursharan
authors.initials: G
authors.lastname: Kalsi
authors.forename: Allison
authors.initials: A
authors.lastname: Badacsonyi
authors.forename: Katie
authors.initials: K
authors.lastname: Kelly
authors.forename: Jenny
authors.initials: J
authors.lastname: Morgan
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Punukollu
authors.forename: David
authors.initials: D
authors.lastname: Curtis
authors.forename: Hugh
authors.initials: H
authors.lastname: Gurling
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C475910:CLINT1 protein, human; D002352:Carrier Proteins; C434483:EPN3 protein, human