The DTNBP1 (dysbindin) gene contributes to schizophrenia, depending on family history of the disease

被引:158
作者
Van Den Bogaert, A
Schumacher, J
Schulze, TG
Otte, AC
Ohlraun, S
Kovalenko, S
Becker, T
Freudenberg, J
Jönsson, EG
Mattila-Evenden, M
Sedvall, GC
Czerski, PM
Kapelski, P
Hauser, J
Maier, W
Rietschel, M
Propping, P
Nöthen, MM
Cichon, S
机构
[1] Univ Antwerp, Dept Med Genet, B-2610 Antwerp, Belgium
[2] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany
[3] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany
[4] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-5300 Bonn, Germany
[5] Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-6800 Mannheim, Germany
[6] Karolinska Hosp & Inst, Dept Clin Neurosci, Psychiat Sect, Human Brain Informat Project, Stockholm, Sweden
[7] Univ Poznan, Dept Psychiat, Poznan, Poland
关键词
D O I
10.1086/379928
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We have investigated the gene for dystrobrevin-binding protein 1 (DTNBP1), or dysbindin, which has been strongly suggested as a positional candidate gene for schizophrenia, in three samples of subjects with schizophrenia and unaffected control subjects of German (418 cases, 285 controls), Polish (294 cases, 113 controls), and Swedish (142 cases, 272 controls) descent. We analyzed five single-nucleotide polymorphisms (P1635, P1325, P1320, P1757, and P1578) and identified significant evidence of association in the Swedish sample but not in those from Germany or Poland. The results in the Swedish sample became even more significant after a separate analysis of those cases with a positive family history of schizophrenia, in whom the five-marker haplotype A-C-A-T-T showed a P value of .00009 (3.1% in controls, 17.8% in cases; OR 6.75; P = .00153 after Bonferroni correction). Our results suggest that genetic variation in the dysbindin gene is particularly involved in the development of schizophrenia in cases with a familial loading of, the disease. This would also explain the difficulty of replicating this association in consecutively ascertained case-control samples, which usually comprise only a small proportion of subjects with a family history of disease.
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收藏
页码:1438 / 1443
页数:6
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