Common variation contributes to the genetic architecture of social communication traits

St Pourcain, Beate, Whitehouse, Andrew J. O., Ang, Wei Q., Warrington, Nicole M., Glessner, Joseph T., Wang, Kai, Timpson, Nicholas J., Evans, David M., Kemp, John P., Ring,Susan M., McArdle, Wendy L., Golding, Jean, Hakonarson, Hakon, Pennell, Craig E. and Smith, George Davey (2013) Common variation contributes to the genetic architecture of social communication traits. Molecular Autism, 4 1: 34.1-34.12. doi:10.1186/2040-2392-4-34

Author St Pourcain, Beate
Whitehouse, Andrew J. O.
Ang, Wei Q.
Warrington, Nicole M.
Glessner, Joseph T.
Wang, Kai
Timpson, Nicholas J.
Evans, David M.
Kemp, John P.
Ring,Susan M.
McArdle, Wendy L.
Golding, Jean
Hakonarson, Hakon
Pennell, Craig E.
Smith, George Davey
Title Common variation contributes to the genetic architecture of social communication traits
Journal name Molecular Autism   Check publisher's open access policy
ISSN 2040-2392
Publication date 2013
Year available 2013
Sub-type Article (original research)
DOI 10.1186/2040-2392-4-34
Open Access Status DOI
Volume 4
Issue 1
Start page 34.1
End page 34.12
Total pages 13
Place of publication London, United Kingdom
Publisher BioMed Central Ltd.
Collection year 2014
Language eng
Subject 2738 Psychiatry and Mental health
2806 Developmental Neuroscience
1309 Developmental Biology
1312 Molecular Biology
Abstract Background: 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. Methods. We performed a genome-wide association study on parent-reported social communication problems using items of the children's communication checklist (age 10 to 11 years) studying single and/or joint marker effects. Analyses were conducted in a large UK population-based birth cohort (Avon Longitudinal Study of Parents and their Children, ALSPAC, N = 5,584) and followed-up within a sample of children with comparable measures from Western Australia (RAINE, N = 1364). Results: Two of our seven independent top signals (P-discovery <1.0E-05) were replicated (0.009 < P-replication ≤0.02) within RAINE and suggested evidence for association at 6p22.1 (rs9257616, meta-P = 2.5E-07) and 14q22.1 (rs2352908, meta-P = 1.1E-06). 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 (h§ssup§2§esup§(SE) = 0.18(0.066), P = 0.0027). Conclusion: Overall, our study provides both joint and single-SNP-based evidence for the contribution of common polymorphisms to variation in social communication phenotypes.
Keyword Autistic trait
Social communication
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 13 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 19 Mar 2014, 16:07:15 EST by Kylie Hengst on behalf of UQ Diamantina Institute