title: Common variation contributes to the genetic architecture of social communication traits.
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 (h2(SE) = 0.18(0.066), P = 0.0027).
  
  
  CONCLUSIONS
  Overall, our study provides both joint and single-SNP-based evidence for the contribution of common polymorphisms to variation in social communication phenotypes.
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. Beate.StPourcain@bristol.ac.uk.
authors.forename: Beate
authors.initials: B
authors.lastname: St Pourcain
authors.forename: Andrew J O
authors.initials: AJ
authors.lastname: Whitehouse
authors.forename: Wei Q
authors.initials: WQ
authors.lastname: Ang
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Warrington
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Glessner
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.forename: John P
authors.initials: JP
authors.lastname: Kemp
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: Wendy L
authors.initials: WL
authors.lastname: McArdle
authors.forename: Jean
authors.initials: J
authors.lastname: Golding
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Craig E
authors.initials: CE
authors.lastname: Pennell
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
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