Common genetic variants on 1p13.2 associate with risk of autism.
K XiaH GuoZ HuG XunL ZuoY PengK WangY HeZ XiongL SunQ PanZ LongX ZouX LiW LiX XuL LuY LiuY HuD TianL LongJ OuY LiuX LiL ZhangY PanJ ChenH PengQ LiuX LuoW SuL WuDesheng LiangH DaiX YanY FengB TangJ LiZ MiedzybrodzkaJ XiaZ ZhangX LuoX ZhangD St ClairJ ZhaoF ZhangPublished in: Molecular psychiatry (2013)
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.
Keyphrases
- autism spectrum disorder
- intellectual disability
- systematic review
- genome wide association study
- copy number
- endothelial cells
- small molecule
- prefrontal cortex
- gene expression
- randomized controlled trial
- transcription factor
- machine learning
- hepatitis c virus
- high throughput
- case control
- genetic diversity
- pluripotent stem cells