Authors:
St Pourcain B, Whitehouse AJ, Ang W, Warrington N, Glessner J, Wang K, et al.
Authors notes:
Molecular Autism. 2013;4(1):34
Keywords:
ALSPAC, RAINE study, Autistic trait, GWAS, Social communication, Association
Abstract:
Social communication difficulties represent an autistic trait that is highly heritable and persistent during the course of development.
However, little is known about the underlying genetic architecture of this phenotype.
Two of our seven independent top signals were replicated within RAINE and suggested evidence for association at 6p22.1 and 14q22.1.
The signal at 6p22.1 was identified within the olfactory receptor gene cluster within the broader major histocompatibility complex (MHC) region.
The strongest candidate locus within this genomic area was TRIM27.
This gene encodes an ubiquitin E3 ligase, which is an interaction partner of methyl-CpG-binding domain (MBD) proteins, such as MBD3 and MBD4, and rare protein-coding mutations within MBD3 and MBD4 have been linked to autism.
The signal at 14q22.1 was found within a gene-poor region.
Single-variant findings were complemented by estimations of the narrow-sense heritability in ALSPAC suggesting that approximately a fifth of the phenotypic variance in social communication traits is accounted for by joint additive effects of genotyped single nucleotide polymorphisms throughout the genome.
Overall, our study provides both joint and single-SNP-based evidence for the contribution of common polymorphisms to variation in social communication phenotypes.