This project aims to study developmental trajectories for autism-related social traits within the general population and to investigate their genetic and environmental determinants. Autism-related traits have been shown to be highly heritable and recent research has provided evidence that even high-risk loci for autism show association with autism spectrum traits in unrelated members of the general population suggesting the presence of underlying Autism Quantitative trait locus.

The proposed study will investigate the Strength and Difficulties Questionnaire (SDQ) Peer Problem scale (PPS) that has been assessed at six different time points during child and adolescent development (6 to 16 years) in members from the Avon Longitudinal Study of Parents, a large UK population-based birth cohort. This scale has been shown to reflect most of the variation in social functioning that is also assessed by more specialised instruments like the Autism Spectrum Screening Questionnaire.

Developmental PPS trajectories will be established using two complementary approaches: Growth Mixture Modelling (GMM) will identify latent classes of trajectories, and a longitudinal mixed model (LMM) approach is proposed to infer trajectories for each single individual based on continuous data. Cross-sectional data, latent classes identified from GMM and longitudinal trajectory properties will be subjected to genome-wide association analysis in all children of the ALSPAC cohort for which phenotype and single nucleotide polymorphism information (Illumina 610k chip) is available (~7000 by the end of 2010). Joint genetic effects that may act in combination to increase susceptibility for social problems will be assessed using pathway analysis that will be implemented using an empirical permutation-based approach. Replication of single and joint GWAS signals will be attempted in a Australian birth cohort (RAINE) for which similar measures on social problems (6 to 16 years; Child Behaviour checklist) and genome-wide data are available (N=1100). In addition, we will embark on an epidemiological approach to uncover environmental risk factors that are associate with PPS trajectories. This research will study both perinatal and postnatal influences as risk factor for persistent social problems in later life. It will be investigated whether ADHD as measured by the SDQ, depression as measured the SMFQ (10,13,14,17 years) and parental influences such as Parental Warmth and maternal depression are antecedents of social problems within later life.

This work will be in addition supervised by David Skuse (UCL).