Polymorphisms at the G72/G30 gene locus, on 13q33, are associated with bipolar disorder in two independent pedigree series
Polymorphisms at the G72/G30 gene locus, on 13q33, are associated with bipolar disorder in two independent pedigree series
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DOI：
10.1086/374822
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发表时间：
2003-05-01
影响因子：
9.8
通讯作者：
Gershon, ES
中科院分区：
文献类型：
--
作者：
Hattori, E;Liu, CY;Gershon, ES
连锁证据表明，染色体13（13 q32 -33）包含双相情感障碍和精神分裂症的易感基因。最近，被称为“G72”和“G30”的基因被鉴定出来，这些重叠基因的多态性被报道与精神分裂症有关。我们研究了两个系列的双相情感障碍家系：临床神经遗传学（CNG）家系（其中与疾病的联系先前已被报道在13 q32 -33），83个样本来自22个多重家庭，和国家精神卫生研究所（NIMH）遗传学倡议家系，474个样本来自152个家庭。16个单核苷酸多态性（SNPs）的基因型和周围的G72/G30位点，其中涵盖了157 kb的区域，涵盖了整个互补的DNA序列的G72和G30。我们进行了传输/不平衡测试（TDT）和单倍型分析，因为连锁不平衡块存在于这个基因位点。在CNG和NIMH数据集中，整个单倍型集的全局TDT结果是显著和一致的（分别为P = .0004和P = .008）。在CNG系列中，相关基因型将家系分为连锁和非连锁（根据连锁证据划分）。单倍型共享的衰减的分析给出了位置估计，包括G72/G30在其95%的置信区间。尽管在NIMH数据集中没有检测到单个SNP的统计学显着关联，但相同的单倍型在两个系列中一致过度传播。这些数据表明，双相情感障碍的易感性变异存在于G72/G30基因附近。与早期的报告一起，这是通过位置方法发现的新基因的第一次证明，该基因与双相情感障碍和精神分裂症独立相关。
Linkage evidence suggests that chromosome 13 (13q32-33) contains susceptibility genes for both bipolar disorder and schizophrenia. Recently, genes called "G72" and "G30" were identified, and polymorphisms of these overlapping genes were reported to be associated with schizophrenia. We studied two series of pedigrees with bipolar disorder: the Clinical Neurogenetics (CNG) pedigrees ( in which linkage to illness had been previously reported at 13q32-33), with 83 samples from 22 multiplex families, and the National Institute of Mental Health (NIMH) Genetics Initiative pedigrees, with 474 samples from 152 families. Sixteen single-nucleotide polymorphisms (SNPs) were genotyped at and around the G72/G30 locus, which covered a 157-kb region encompassing the entire complementary DNA sequences of G72 and G30. We performed transmission/disequilibrium testing (TDT) and haplotype analysis, since a linkage-disequilibrium block was present at this gene locus. In the CNG and NIMH data sets, the results of global TDT of the entire haplotype set were significant and consistent (P = .0004 and P = .008, respectively). In the CNG series, the associated genotypes divided the families into those with linkage and those without linkage ( partitioned by the linkage evidence). Analysis of the decay of haplotype sharing gave a location estimate that included G72/G30 in its 95% confidence interval. Although statistically significant association was not detected for individual SNPs in the NIMH data set, the same haplotype was consistently overtransmitted in both series. These data suggest that a susceptibility variant for bipolar illness exists in the vicinity of the G72/G30 genes. Taken together with the earlier report, this is the first demonstration of a novel gene(s), discovered through a positional approach, independently associated with both bipolar illness and schizophrenia.