Common genetic variants on 1p13.2 associate with risk of autism
Common genetic variants on 1p13.2 associate with risk of autism
复制标题
1p13.2 上的常见遗传变异与自闭症风险相关。
DOI：
10.1038/mp.2013.146
复制
发表时间：
2014-11-01
影响因子：
11
通讯作者：
Zhang, F.
中科院分区：
文献类型：
--
作者：
Xia, K.;Guo, H.;Zhang, F.
自闭症是一种高度可遗传的神经发育障碍，已知的遗传变异，大多是罕见的，只占病例的一小部分。在这里，我们报告了一项关于自闭症的全基因组关联研究，使用了两个中国队列作为基因发现(n=2150)和三个欧洲祖先群体的数据集，用于顶级关联信号的复制分析。Meta分析发现3个单核苷酸多态rs936938(P=4.49×10(-8))、非同义rs6537835(P=3.26×10(-8))和rs1877455(P=8.70×10(-8))，以及相关的单倍型AMPD1-NRAS-CSDE1、TRIM33和TRIM33-BCAS2与自闭症相关；所有这些都被定位到先前报道的与自闭症相关的连锁区域(1p13.2)。对CSDE1、NRAS和TRIM33基因表达的顺式调节作用，以及自闭症患者和非自闭症患者之间死后大脑前额叶皮质CSDE1和TRIM33的差异表达，进一步支持了这些遗传关联。我们的研究提示TRIM33和NRAS-CSDE1是自闭症的候选基因，并可能为自闭症的病因学提供新的见解。
Autism is a highly heritable neurodevelopmental disorder, and known genetic variants, mostly rare, account only for a small proportion of cases. Here we report a genome-wide association study on autism using two Chinese cohorts as gene discovery (n = 2150) and three data sets of European ancestry populations for replication analysis of top association signals. Meta-analysis identified three single-nucleotide polymorphisms, rs936938 (P = 4.49 x 10(-8) ), non-synonymous rs6537835 (P = 3.26 x 10(-8)) and rs1877455 (P = 8.70 x 10(-8)), and related haplotypes, AMPD1-NRAS-CSDE1, TRIM33 and TRIM33-BCAS2, associated with autism; all were mapped to a previously reported linkage region (1p13.2) with autism. These genetic associations were further supported by a cis-acting regulatory effect on the gene expressions of CSDE1, NRAS and TRIM33 and by differential expression of CSDE1 and TRIM33 in the human prefrontal cortex of post-mortem brains between subjects with and those without autism. Our study suggests TRIM33 and NRAS-CSDE1 as candidate genes for autism, and may provide a novel insight into the etiology of autism.