Families with the risk allele of DISC1 reveal a link between schizophrenia and another component of the same molecular pathway, NDE1

被引:61
作者
Hennah, William
Tomppo, Liisa
Hiekkalinna, Tero
Palo, Outi M.
Kilpinen, Helena
Ekelund, Jesper
Tuulio-Henriksson, Annamari
Silander, Kaisa
Partonen, Timo
Paunio, Tiina
Terwilliger, Joseph D.
Lonnqvist, Jouko
Peltonen, Leena [1 ]
机构
[1] Natl Publ Hlth Inst, Dept Mol Med, Helsinki, Finland
[2] Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, Helsinki, Finland
[3] Univ Helsinki, Cent Hosp, Dept Psychiat, Helsinki, Finland
[4] Columbia Univ, Dept Psychiat, Dept Genet & Dev, Columbia Genome Ctr, New York, NY USA
[5] New York State Psychiat Inst & Hosp, Div Med Genet, New York, NY 10032 USA
[6] Univ Helsinki, Dept Med Genet, Helsinki, Finland
[7] Univ Helsinki, Finnish Genome Ctr, Helsinki, Finland
[8] MIT, Broad Inst, Boston, MA USA
基金
芬兰科学院;
关键词
D O I
10.1093/hmg/ddl462
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have previously reported a robust association between an allelic haplotype of 'Disrupted in Schizophrenia 1' (DISC1) and schizophrenia in a nationwide collection of Finnish schizophrenia families. This specific DISC1 allele was later identified to associate with visual working memory, selectively in males. DISC1 association to schizophrenia has since been replicated in multiple independent study samples from different populations. In this study, we conditioned our sample of Finnish families for the presence of the Finnish tentative risk allele for DISC1 and re-analyzed our genome-wide scan data of 443 markers on the basis of this stratification. Two additional loci displayed an evidence of linkage (LOD > 3) and included a locus on 16p13, proximal to the gene encoding NDE1, which has been shown to biologically interact with DISC1. Although none of the observed linkages remained significant after multiple test correction through simulation, further analysis of NDE1 revealed an association between a tag-haplotype and schizophrenia (P = 0.00046) specific to females, which proved to be significant (P = 0.011) after multiple test correction. Our finding would support the concept that initial gene findings in multifactorial diseases will assist in the identification of other components of complex genetic etiology. Notably, this and other converging lines of evidence underline the importance of DISC1-related functional pathways in the etiology of schizophrenia.
引用
收藏
页码:453 / 462
页数:10
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