Case-control study and transmission disequilibrium test provide consistent evidence for association between schizophrenia and genetic variation in the 22q11 gene ZDHHC8
Case-control study and transmission disequilibrium test provide consistent evidence for association between schizophrenia and genetic variation in the 22q11 gene ZDHHC8
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病例对照研究和传递不平衡检验为精神分裂症与 22q11 基因 ZDHHC8 遗传变异之间的关联提供了一致的证据。
DOI：
10.1093/hmg/ddh322
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发表时间：
2004-12-01
影响因子：
3.5
通讯作者：
He, L
中科院分区：
文献类型：
--
作者：
Chen, WY;Shi, YY;He, L
在基于家族的连锁不平衡(LD)研究中，22q11基因ZDHHC8的遗传变异被认为与精神分裂症有关，ZDHHC8编码一种假定的跨膜棕榈酰转移酶。最近发现的单核苷酸多态(SNP)rs175174(A/G)通过调节ZDHHC8基因内含子4的保留来调节全功能转录本的水平。在这项工作中，我们对ZDHHC8基因座内的三个遗传变异进行了基因分型，并对中国汉族人群的群体样本和家系样本进行了关联研究。这三个大约5.5kb的多态在LD中被检测到。我们的结果为ZDHHC8基因座内的变异与精神分裂症的关联提供了令人信服的支持证据，但在SNP rs175174上发现了不同的危险等位基因。病例组G等位基因频率显著高于对照组(69.47：59.96%；P=0.000018)，家系传递不平衡检验证实该等位基因过度传递(传递/未传递=87：54；P=0.0055)。两个样本组甚至具有相同的风险单倍型，频率相似。我们目前的数据显示，在相同的实验条件下，从同一实验室的病例对照样本和基于家庭的样本中获得了一致的关联结果。尽管存在潜在的遗传异质性，我们的独立发现进一步支持22q11区域可能包含候选精神分裂症易感基因。
Genetic variants in the 22q11 gene ZDHHC8, which encodes a putative transmembrane palmitoyltransferase, has been associated to schizophrenia in family-based linkage disequilibrium (LD) studies. The single nucleotide polymorphism (SNP) rs175174 (A/G), which had the strongest association, has been shown recently to regulate the level of the fully functional transcript by modulating the retention of intron 4 of ZDHHC8. In this work, we genotyped three genetic variants within the ZDHHC8 locus and conducted association studies in both population- and family-based samples of the Han Chinese population. The three polymorphisms spanning approximately 5.5 Kb were detected to be in significant LD. Our results provided compelling supportive evidence for association of the variants within the ZDHHC8 locus with schizophrenia but revealed different risk allele at SNP rs175174. The G allele was significantly more common in cases than in controls (69.47 : 59.96%; P=0.000018) and excess transmission of the same allele was confirmed in the family-based transmission disequilibrium test (transmitted/non-transmitted=87 : 54; P=0.0055). Both sample sets even shared the same risk haplotype with similar frequency. Our current data presents consistent association results obtained from both case-control and family-based samples in a same laboratory under the same experimental condition. Despite the potential genetic heterogeneity, our independent findings further support that the 22q11 region is likely to harbor candidate schizophrenia susceptibility genes.