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

Abstract

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.

Unr defines a novel class of nucleoplasmic reticulum involved in mRNA translation

“…Unr has been implicated in the control of cell death (Dormoy-Raclet et al, 2007), cell differention (Elatmani et al, 2011) and cell migration (Kobayashi et al, 2013). In humans, recent studies identified important roles for Unr in the promotion of melanoma cell invasion and metastasis (Wurth et al, 2016), as well as in disorders, such as autism or Diamond-Blackfan anemia (Sanders et al, 2012;Xia et al, 2014;Horos and von Lindern, 2012). Unr has also been characterized as being a critical regulator of embryonic development.…”

Potential serum biomarkers from a metabolomics study of autism

“…Some of these rare single point genetic mutations, or even common genetic variants, have also been associated inconsistently with autism. 4,9,15,16 At present, the diagnosis of autism relies mainly on some observational tools that may involve a great variability. Few biomarkers are established for autism.…”

Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of Autism

“…Xia et al used two Chinese cohorts for 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 and related haplotypes; all were mapped to a previously reported linkage region (1p13.2) with autism [26]. Kovac et al identified two single nucleotide polymorphisms (SNPs).…”

“…Manual examination of this list identified ANK3 as the most likely candidate gene [25]. Xia et al suggested TRIM33 and NRAS-CSDE1 as candidate genes for autism, and may provide a novel insight into the etiology of autism [26].…”