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

• Published in: Molecular psychiatry Vol. 19; no. 11; pp. 1212 - 1219
• Main Authors: Xia, K, Guo, H, Hu, Z, Xun, G, Zuo, L, Peng, Y, Wang, K, He, Y, Xiong, Z, Sun, L, Pan, Q, Long, Z, Zou, X, Li, X, Li, W, Xu, X, Lu, L, Liu, Y, Hu, Y, Tian, D, Long, L, Ou, J, Zhang, L, Pan, Y, Chen, J, Peng, H, Liu, Q, Luo, X, Su, W, Wu, L, Liang, D, Dai, H, Yan, X, Feng, Y, Tang, B, Li, J, Miedzybrodzka, Z, Xia, J, Zhang, Z, Zhang, X, St Clair, D, Zhao, J, Zhang, F
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2014; Nature Publishing Group
• Subjects: 631/208/726/649; 692/420/2489/144; 692/699/476/1312; African Americans; Asian Continental Ancestry Group - genetics; Autism; Autistic Disorder - genetics; Autistic Disorder - metabolism; Behavioral Sciences; Between-subjects design; Biological Psychology; China; Chromosomes, Human, Pair 1 - genetics; Cohort Studies; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Etiology; European Continental Ancestry Group - genetics; Genetic aspects; Genetic diversity; Genetic Predisposition to Disease; Genetic variation; Genome-wide association studies; Genome-Wide Association Study; Genomes; GTP Phosphohydrolases - genetics; GTP Phosphohydrolases - metabolism; Haplotypes; Humans; Identification and classification; Medicine; Medicine & Public Health; Membrane Proteins - genetics; Membrane Proteins - metabolism; Meta-Analysis as Topic; Neurodevelopmental disorders; Neurosciences; original-article; Pharmacotherapy; Polymorphism, Single Nucleotide; Prefrontal cortex; Prefrontal Cortex - metabolism; Psychiatry; Risk; Risk factors; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Single-nucleotide polymorphism; Systematic review; Transcription Factors - genetics; Transcription Factors - metabolism; China; human genetics; common genetic variants; association fine mapping; autism; genome-wide association study
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2013.146

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.