Family-based association testing strongly implicates DRD2 as a risk gene for schizophrenia in Han Chinese from Taiwan
Family-based association testing strongly implicates DRD2 as a risk gene for schizophrenia in Han Chinese from Taiwan
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DOI：
10.1038/mp.2008.30
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发表时间：
2009-09-01
影响因子：
11
通讯作者：
Tsuang, M. T.
中科院分区：
文献类型：
--
作者：
Glatt, S. J.;Faraone, S. V.;Tsuang, M. T.
编码多巴胺受体D2的基因（位于染色体11 q23上的DRD 2）长期以来一直是精神分裂症的主要功能和位置候选风险基因。总的来说，先前的病例对照研究发现Ser 311 Cys DRD 2多态性（rs 1801028）对精神分裂症风险的可靠影响，但该基因的其他多态性很少被评估，迄今为止还没有进行过充分的基于家族的关联研究。我们的目的是测试21个单倍型标记和所有三个已知的非同义单核苷酸多态性（SNPs）在DRD 2与精神分裂症的关联在一个以家庭为基础的研究2408汉族人，包括1214个受影响的个人从616个家庭。我们没有发现rs 1801028的显著影响，但我们确实发现了精神分裂症与跨越强连锁不平衡（LD）块的两个多标记单倍型和9个单个SNP（Ps < 0.05）相关的显著证据。重要的是，两个SNP（rs 1079727和rs 2283265）和跨越整个LD区块的两个多标记单倍型（包括包含rs 1801028的单倍型）在校正多次测试后仍然显着。这些结果进一步增加了DRD 2作为精神分裂症风险基因的数据主体;然而，DRD 2中的因果变异仍有待于通过进一步精细定位该基因来阐明，特别注意第三至第五外显子周围的区域。Molecular Psychiatry（2009）14，885-893; doi：10.1038/mp.2008.30; 2008年3月11日在线发表
The gene that codes for dopamine receptor D2 (DRD2 on chromosome 11q23) has long been a prime functional and positional candidate risk gene for schizophrenia. Collectively, prior case-control studies found a reliable effect of the Ser311Cys DRD2 polymorphism (rs1801028) on risk for schizophrenia, but few other polymorphisms in the gene had ever been evaluated and no adequately powered family-based association study has been performed to date. Our objective was to test 21 haplotype-tagging and all three known nonsynonymous single-nucleotide polymorphisms (SNPs) in DRD2 for association with schizophrenia in a family-based study of 2408 Han Chinese, including 1214 affected individuals from 616 families. We did not find a significant effect of rs1801028, but we did find significant evidence for association of schizophrenia with two multi-marker haplotypes spanning blocks of strong linkage disequilibrium (LD) and nine individual SNPs (Ps < 0.05). Importantly, two SNPs (rs1079727 and rs2283265) and both multi-marker haplotypes spanning entire LD blocks (including one that contained rs1801028) remained significant after correcting for multiple testing. These results further add to the body of data implicating DRD2 as a schizophrenia risk gene; however, a causal variant(s) in DRD2 remains to be elucidated by further fine mapping of the gene, with particular attention given to the area surrounding the third through fifth exons. Molecular Psychiatry (2009) 14, 885-893; doi: 10.1038/mp.2008.30; published online 11 March 2008