TY - JOUR
T1 - The DTNBP1 (Dysbindin) Gene Contributes to Schizophrenia, Depending on Family History of the Disease
AU - Van Den Bogaert, Ann
AU - Schumacher, Johannes
AU - Schulze, Thomas G.
AU - Otte, Andreas C.
AU - Ohlraun, Stephanie
AU - Kovalenko, Svetlana
AU - Becker, Tim
AU - Freudenberg, Jan
AU - Jönsson, Erik G.
AU - Mattila-Evenden, Marja
AU - Sedvall, Göran C.
AU - Czerski, Piotr M.
AU - Kapelski, Pawel
AU - Hauser, Joanna
AU - Maier, Wolfgang
AU - Rietschel, Marcella
AU - Propping, Peter
AU - Nöthen, Markus M.
AU - Cichon, Sven
PY - 2003/12
Y1 - 2003/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=9144267763&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=9144267763&partnerID=8YFLogxK
U2 - 10.1086/379928
DO - 10.1086/379928
M3 - Article
C2 - 14618545
AN - SCOPUS:9144267763
SN - 0002-9297
VL - 73
SP - 1438
EP - 1443
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
ER -