Disrupted in Schizophrenia 1 (DISC1): Association with schizophrenia, schizoaffective disorder, and bipolar disorder
Disrupted in Schizophrenia 1 (DISC1): Association with schizophrenia, schizoaffective disorder, and bipolar disorder
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DOI：
10.1086/425586
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发表时间：
2004-11-01
影响因子：
9.8
通讯作者：
Malhotra, AK
中科院分区：
文献类型：
--
作者：
Hodgkinson, CA;Goldman, D;Malhotra, AK
精神分裂症、情感性精神障碍和双相情感障碍是常见的精神障碍，具有高遗传率和可变的表型。位于染色体1 q42上的分裂症1（DISC 1）基因最初被发现并与苏格兰家族的精神分裂症有关，该家族携带破坏DISC 1和DISC 2的平衡易位。最近，DISC 1与精神分裂症，广义上说，在一般的芬兰人口，通过一个共同的单倍型从内含子1/外显子2的区域的受影响的妇女的传播不足。我们目前的数据来自一个北美白色人群的病例对照研究，证实了一个共同的单倍型的内含子1/外显子2区域在个体情感障碍的代表性不足。在外显子1和外显子9之间延伸的四个单倍型块内包含的多个单倍型与精神分裂症、情感障碍和双相情感障碍相关。我们还发现过度表达的外显子9错义等位基因Phe 607的情感障碍。这些数据支持的想法，这些明显不同的疾病至少有一个部分收敛的病因和DISC 1基因座的变化易患各种精神疾病的个人。
Schizophrenia, schizoaffective disorder, and bipolar disorder are common psychiatric disorders with high heritabilities and variable phenotypes. The Disrupted in Schizophrenia 1 (DISC1) gene, on chromosome 1q42, was originally discovered and linked to schizophrenia in a Scottish kindred carrying a balanced translocation that disrupts DISC1 and DISC2. More recently, DISC1 was linked to schizophrenia, broadly defined, in the general Finnish population, through the undertransmission to affected women of a common haplotype from the region of intron 1/exon 2. We present data from a case-control study of a North American white population, confirming the underrepresentation of a common haplotype of the intron 1/exon 2 region in individuals with schizoaffective disorder. Multiple haplotypes contained within four haplotype blocks extending between exon 1 and exon 9 are associated with schizophrenia, schizoaffective disorder, and bipolar disorder. We also find overrepresentation of the exon 9 missense allele Phe607 in schizoaffective disorder. These data support the idea that these apparently distinct disorders have at least a partially convergent etiology and that variation at the DISC1 locus predisposes individuals to a variety of psychiatric disorders.