Williams J, Spurlock G, Holmans P, Mant R, Murphy K, Jones L, Cardno A, Asherson P, Blackwood D, Muir W, Meszaros K, Aschauer H, Mallet J, Laurent C, Pekkarinen P, Seppala J, Stefanis C N, Papadimitriou G N, Macciardi F, Verga M, Pato C, Azevedo H, Crocq M A, Gurling H, Owen M J
Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Mol Psychiatry. 1998 Mar;3(2):141-9. doi: 10.1038/sj.mp.4000376.
We performed a meta-analysis of over 30 case-control studies of association between schizophrenia and a bi-allelic, Bali polymorphism in exon 1 of the dopamine D3 receptor gene. We observed a significant excess of both forms of homozygote in patients (P = 0.0009, odds ratio (OR) = 1.21, 95% Confidence Interval (CI) = 1.07-1.35) in the combined sample of 5351 individuals. No significant heterogeneity was detected between samples and the effects did not appear to be the product of publishing bias. In addition we undertook an independent, family-based association study of this polymorphism in 57 parent/proband trios, taken from unrelated European multiplex families segregating schizophrenia. A transmission disequilibrium test (TDT) showed a significant excess of homozygotes in schizophrenic patients (P = 0.004, odds ratio (OR) = 2.7, 95% CI = 1.35-5.86). Although no significant allelic association was observed, a significant association was detected with the 1-1 genotype alone (P = 0.02, OR = 2.32, 95% CI = 1.13-4.99). In addition when the results of the family-based association study were included in the meta-analysis, the homozygosity effect increased in significance (P = 0.0002, OR = 1.23, 95% CI = 1.09-1.38). The results of the meta-analysis and family-based association study provide independent support for a relationship between schizophrenia and homozygosity at the Bali polymorphism of the D3 receptor gene, or between a locus in linkage disequilibrium with it.
我们对30多项关于精神分裂症与多巴胺D3受体基因外显子1双等位基因巴厘多态性之间关联的病例对照研究进行了荟萃分析。在5351名个体的合并样本中，我们观察到患者中两种纯合子形式均显著过量（P = 0.0009，优势比（OR）= 1.21，95%置信区间（CI）= 1.07 - 1.35）。样本之间未检测到显著的异质性，且效应似乎并非发表偏倚的产物。此外，我们对来自欧洲无关的精神分裂症分离多重家庭的57个父母/先证者三联体进行了该多态性的独立家系关联研究。传递不平衡检验（TDT）显示精神分裂症患者中纯合子显著过量（P = 0.004，优势比（OR）= 2.7，95% CI = 1.35 - 5.86）。虽然未观察到显著的等位基因关联，但仅与1 - 1基因型存在显著关联（P = 0.02，OR = 2.32，95% CI = 1.13 - 4.99）。此外，当将家系关联研究的结果纳入荟萃分析时，纯合性效应的显著性增加（P = 0.0002，OR = 1.23，95% CI = 1.09 - 1.38）。荟萃分析和家系关联研究的结果为精神分裂症与D3受体基因巴厘多态性的纯合性之间或与其处于连锁不平衡的一个位点之间的关系提供了独立支持。
