No association between 12 dopaminergic genes and schizophrenia in a large Dutch sample

被引:21
作者
Hoogendoorn, MLC
Bakker, SC
Schnack, HG
Selten, JPC
Otten, HG
Verduijn, W
van der Heijden, FMMA
Pearson, PL
Kahn, RS
Sinke, RJ
机构
[1] Univ Utrecht, Med Ctr, Dept Psychiat, Rudolf Magnus Inst Neurosci, NL-3584 CX Utrecht, Netherlands
[2] Univ Utrecht, Med Ctr, Dept Med Genet, NL-3584 CX Utrecht, Netherlands
[3] Univ Utrecht, Med Ctr, Dept Immunol, NL-3584 CX Utrecht, Netherlands
[4] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands
[5] Vincent van Gogh Inst Psychiat, Venray, Netherlands
关键词
schizophrenia; dopaminergic transmission; genetics; association; DNA pooling;
D O I
10.1002/ajmg.b.30147
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
It has been suggested that genes involved in dopamine neurotransmission contribute to the pathogenesis of schizophrenia. However, reported associations of the disorder with genetic markers in dopaminergic genes have yielded inconsistent results. Possible explanations are differences in phenotyping, genetic heterogeneity, low marker informativity, and the use of small sample sizes. Here, we present a two-stage analysis of 12 dopaminergic genes in a large sample of Dutch schizophrenic patients. To reduce genetic heterogeneity, only patients with at least three Caucasian grandparents of Dutch ancestry were ascertained. An efficient genotyping strategy was used, in which polymorphic microsatellite markers were first screened for association in DNA pools. Promising results were followed up by individual genotyping in an extended sample. The pooled samples consisted of 208 schizophrenic patients and 288 unmatched control individuals. For each of the genes, more than one microsatellite marker was selected where possible, either intragenic or close to the gene. After correcting for multiple testing, significantly different allele frequencies were detected for DRD5 marker D4S615. Subsequently, we individually genotyped this particular marker and another DRD5 marker, as well as a DRD3 marker that could not be analyzed using the pooling strategy. This was done in an extended sample of 282 schizophrenic patients and a control sample of 585 individuals. In this second stage of the study, we found no association between these three markers and schizophrenia. The results of our comprehensive analysis provide no evidence for association between schizophrenia and 12 dopaminergic genes in a large Dutch sample. (c) 2005 Wiley-Liss, Inc.
引用
收藏
页码:6 / 9
页数:4
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