我国科学家采用GWAS在1号染色体上发现儿童孤独症相关基因变异

近期，我国科学家采用全基因组关联研究(GWAS)方法，成功在1号染色体位置发现了和孤独症发病相关的基因变异。相关文章发表于2013年11月05日的《molecular Psychiatry》杂志上。

该研究采用全基因组关联研究(GWAS)方法，成功在1号染色体位置发现了和孤独症发病相关的基因变异，并鉴定了几个可能的易感基因。这不仅为孤独症的致病机制研究提供了重要依据，也为其诊断和早期干预带来了新希望。

该研究成果是中南大学医学遗传学国家重点实验室研究员夏昆与湘雅二医院精神卫生研究所教授赵靖平联合承担的“973”计划项目——“儿童孤独症遗传基础及其致病的机制研究”的最新进展。

近年来，中南大学团队就孤独症遗传基础及其致病机制的前沿科学问题开展了大量研究并取得了一系列成果。2011年获得国内首个孤独症的“973”计划项目，由夏昆担任首席科学家，现已建成国内最大的孤独症临床及遗传资源样本库。

原文摘要：

Common genetic variants on 1p13.2 associate with risk of autism

K Xia, H Guo, Z Hu, G Xun, L Zuo, Y Peng, K Wang, Y He, Z Xiong, L Sun, Q Pan, Z Long, X Zou, X Li, W Li, X Xu, L Lu, Y Liu, Y Hu, D Tian, L Long, J Ou, Y Liu, X Li, L Zhang, Y Pan, J Chen, H Peng, Q Liu, X Luo,W Su, L Wu, D Liang, H Dai, X Yan, Y Feng, B Tang, J Li, Z Miedzybrodzka, J Xia, Z Zhang, X Luo, X Zhang, D St Clair, J Zhao andF Zhang

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 × 10−8), non-synonymous rs6537835 (P=3.26 × 10−8) and rs1877455 (P=8.70 × 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.