Cis- and trans- loci influence expression of the schizophrenia susceptibility gene DTNBP1

Human Molecular Genetics
Nicholas J BrayM C O'Donovan

Abstract

Susceptibility to complex disease appears to be partly mediated by heritable differences in gene expression. Where cis-acting effects on a gene's expression influence disease susceptibility, other genes containing polymorphism with a trans-acting effect on expression of that gene may also be expected to modulate risk. Use of the expression of an identified disease gene as an endophenotype for quantitative linkage analysis may therefore provide a powerful method for mapping loci that modulate disease susceptibility. We performed genome-wide linkage analysis on expression of dystrobrevin binding protein 1 (DTNBP1), a well-supported susceptibility gene for schizophrenia, in large CEPH pedigrees. We observed genome-wide significant evidence for linkage at the DTNBP1 locus on chromosome 6p22, and demonstrated that this reflects variable cis-acting effects on DTNBP1 expression. In addition, we observed genome-wide suggestive evidence for linkage of DTNBP1 expression to chromosome 8p, suggesting a locus that exerts a trans-acting effect on DTNBP1 expression. The region of linkage to DTNBP1 expression on chromosome 8 is contiguous with linkage findings based upon the clinical schizophrenia phenotype, and contains another well-supported...Continue Reading

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Citations

Jul 17, 2008·Current Psychiatry Reports·Charlotte L AllanPeter McGuffin
Oct 6, 2010·The Journal of Biological Chemistry·Erkang FeiGuanghui Wang
Nov 18, 2008·Schizophrenia Bulletin·Hiroki IshiguroTadao Arinami
May 9, 2008·Neuroscience and Biobehavioral Reviews·Raymond C K Chan, Irving I Gottesman
May 19, 2009·Human Brain Mapping·Katherine L NarrRobert M Bilder
Feb 10, 2011·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Mar Fatjó-VilasLourdes Fañanás
Jul 29, 2010·Expert Review of Neurotherapeutics·Nora S VyasBasant K Puri

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