Article

No evidence for linkage in the Irish study of high-density schizophrenia families (ISHDSF)

Department of Psychiatry, Virginia Institute of Psychiatric and Behavioural Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Molecular Psychiatry (Impact Factor: 15.15). 09/2004; 9(8):777-83; image 729. DOI: 10.1038/sj.mp.4001530
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ABSTRACT The neuregulin-1 gene (NRG1) at chromosome 8p21-22 has been implicated as a schizophrenia susceptibility gene in Icelandic, Scottish, Irish and mixed UK populations. The shared ancestry between these populations led us to investigate the NRG1 polymorphisms and appropriate marker haplotypes for linkage and/or association to schizophrenia in the Irish study of high-density schizophrenia families (ISHDSF). Neither single-point nor multi-point linkage analysis of NRG1 markers gave evidence for linkage independent of our pre-existing findings telomeric on 8p. Analysis of linkage disequilibrium (LD) across the 252 kb interval encompassing the 7 marker core Icelandic/Scottish NRG1 haplotype revealed two separate regions of modest LD, comprising markers SNP8NRG255133, SNP8NRG249130 and SNP8NRG243177 (telomeric) and microsatellites 478B14-428, 420M9-1395, D8S1810 and 420M9-116I12 (centromeric). From single marker analysis by TRANSMIT and FBAT we found no evidence for association with schizophrenia for any marker. Haplotype analysis for the three SNPs in LD region 1 and, separately, the four microsatellites in LD region 2 (analyzed in overlapping 2-marker windows), showed no evidence for overtransmission of specific haplotypes to affected individuals. We therefore conclude that if NRG1 does contain susceptibility alleles for schizophrenia, they impact quite weakly on risk in the ISHDSF.

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Available from: Dawn L Thiselton, Aug 08, 2014
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    • "Since this initial report, confirmatory studies of NRG1 association have been reported in different populations in Scotland (Stefansson et al. 2003), China (Li et al. 2004), Hungary (Keri et al. 2009), Japan (Fukui et al. 2006), Sweden (Alaerts et al. 2009), and a second Scottish cohort (Thomson et al. 2007), though the associated haplotype varies between studies. Negative studies of association have also been reported in Japan (Ikeda et al. 2008; Iwata et al. 2004), Ireland (Thiselton et al. 2004), Denmark (Ingason et al. 2006), Spain (Rosa et al. 2007), and the United States (Crowley et al. 2008). "
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