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

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

Molecular psychiatry (2013-11-06)

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, F Zhang

PMID24189344

摘要

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.