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

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.