The DISC locus and schizophrenia: evidence from an association study in a central European sample and from a meta-analysis across different European populations - PubMed (original) (raw)

Meta-Analysis

. 2009 Jul 15;18(14):2719-27.

doi: 10.1093/hmg/ddp204. Epub 2009 May 4.

Gonzalo Laje, Rami Abou Jamra, Tim Becker, Thomas W Mühleisen, Catalina Vasilescu, Manuel Mattheisen, Stefan Herms, Per Hoffmann, Axel M Hillmer, Alexander Georgi, Christine Herold, Thomas G Schulze, Peter Propping, Marcella Rietschel, Francis J McMahon, Markus M Nöthen, Sven Cichon

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Meta-Analysis

The DISC locus and schizophrenia: evidence from an association study in a central European sample and from a meta-analysis across different European populations

Johannes Schumacher et al. Hum Mol Genet. 2009.

Abstract

Association studies, as well as the initial translocation family study, identified the gene Disrupted-In-Schizophrenia-1 (DISC1) as a risk factor for schizophrenia. DISC1 encodes a multifunctional scaffold protein involved in neurodevelopmental processes implicated in the etiology of schizophrenia. The present study explores the contribution of the DISC locus to schizophrenia using three different approaches: (i) systematic association mapping aimed at detecting DISC risk variants in a schizophrenia sample from a central European population (556 SNPs, n = 1621 individuals). In this homogenous sample, a circumscribed DISC1 interval in intron 9 was significantly associated with schizophrenia in females (P = 4 x 10(-5)) and contributed most strongly to early-onset cases (P = 9 x 10(-5)). The odds ratios (ORs) were in the range of 1.46-1.88. (ii) The same sample was used to test for the locus-specific SNP-SNP interaction most recently associated with schizophrenia. Our results confirm the SNP interplay effect between rs1538979 and rs821633 that significantly conferred disease risk in male patients with schizophrenia (P = 0.016, OR 1.57). (iii) In order to detect additional schizophrenia variants, a meta-analysis was performed using nine schizophrenia samples from different European populations (50 SNPs, n = 10 064 individuals maximum, n = 3694 minimum). We found evidence for a common schizophrenia risk interval within DISC1 intron 4-6 (P = 0.002, OR 1.27). The findings point to a complex association between schizophrenia and DISC, including the presence of different risk loci and SNP interplay effects. Furthermore, our phenotype-genotype results--including the consideration of sex-specific effects--highlight the value of homogenous samples in mapping risk genes for schizophrenia in general, and at the DISC locus in particular.

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