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rdf:type |
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lifeskim:mentions |
umls-concept:C0004083,
umls-concept:C0032659,
umls-concept:C0036341,
umls-concept:C0180459,
umls-concept:C0239307,
umls-concept:C0239308,
umls-concept:C0332120,
umls-concept:C0370003,
umls-concept:C0920317,
umls-concept:C1556138,
umls-concept:C1621443,
umls-concept:C1705370,
umls-concept:C1708726,
umls-concept:C2347026,
umls-concept:C2603343
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pubmed:issue |
14
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pubmed:dateCreated |
2009-6-24
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pubmed:abstractText |
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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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-10814723,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-10835412,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-12029063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-12499305,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-12796219,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-12930761,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-14532331,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-15386212,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-15744031,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-15812168,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-15838535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-16524593,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-16699061,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-16959794,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-17055463,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-17701901,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-17912248,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-18198266,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-18347602,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-18668039,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-1883262,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-1973210,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19414483-8125454
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1460-2083
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pubmed:author |
pubmed-author:Abou JamraRamiR,
pubmed-author:BeckerTimT,
pubmed-author:CichonSvenS,
pubmed-author:GeorgiAlexanderA,
pubmed-author:HermsStefanS,
pubmed-author:HeroldChristineC,
pubmed-author:HillmerAxel MAM,
pubmed-author:HoffmannPerP,
pubmed-author:LajeGonzaloG,
pubmed-author:MühleisenThomas WTW,
pubmed-author:MattheisenManuelM,
pubmed-author:McMahonFrancis JFJ,
pubmed-author:NöthenMarkus MMM,
pubmed-author:ProppingPeterP,
pubmed-author:RietschelMarcellaM,
pubmed-author:SchulzeThomas GTG,
pubmed-author:SchumacherJohannesJ,
pubmed-author:VasilescuCatalinaC
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2719-27
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pubmed:dateRevised |
2010-9-27
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pubmed:meshHeading |
pubmed-meshheading:19414483-Case-Control Studies,
pubmed-meshheading:19414483-European Continental Ancestry Group,
pubmed-meshheading:19414483-Female,
pubmed-meshheading:19414483-Genetic Predisposition to Disease,
pubmed-meshheading:19414483-Genotype,
pubmed-meshheading:19414483-Humans,
pubmed-meshheading:19414483-Introns,
pubmed-meshheading:19414483-Male,
pubmed-meshheading:19414483-Nerve Tissue Proteins,
pubmed-meshheading:19414483-Polymorphism, Single Nucleotide,
pubmed-meshheading:19414483-Schizophrenia,
pubmed-meshheading:19414483-Sex Factors
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pubmed:year |
2009
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pubmed:articleTitle |
The DISC locus and schizophrenia: evidence from an association study in a central European sample and from a meta-analysis across different European populations.
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pubmed:affiliation |
Unit on the Genetic Basis of Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD 20892-3719, USA. schumacherj@mail.nih.gov
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Meta-Analysis,
Research Support, N.I.H., Extramural,
Research Support, N.I.H., Intramural
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