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Mol Psychiatry DOI:10.1038/mp.2016.198

ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties.

Publication TypeJournal Article
Year of Publication2018
AuthorsSt Pourcain, B, Robinson, EB, Anttila, V, Sullivan, BB, Maller, J, Golding, J, Skuse, D, Ring, S, Evans, DM, Zammit, S, Fisher, SE, Neale, BM, Anney, RJL, Ripke, S, Hollegaard, MV, Werge, T, Ronald, A, Grove, J, Hougaard, DM, Børglum, AD, Mortensen, PB, Daly, MJ, Davey Smith, G
Corporate AuthorsiPSYCH-SSI-Broad Autism Group
JournalMol Psychiatry
Volume23
Issue2
Pages263-270
Date Published2018 02
ISSN1476-5578
KeywordsAdolescent, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Child, Child Development Disorders, Pervasive, Communication, Female, Genome-Wide Association Study, Humans, Language, Longitudinal Studies, Male, Multifactorial Inheritance, Risk Factors, Schizophrenia, Social Behavior, Verbal Behavior
Abstract

Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic influences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children, N⩽5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic influences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD- and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptoms.

DOI10.1038/mp.2016.198
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/28044064?dopt=Abstract

Alternate JournalMol. Psychiatry
PubMed ID28044064
PubMed Central IDPMC5382976
Grant ListK01 MH099286 / MH / NIMH NIH HHS / United States
102215 / / Wellcome Trust / United Kingdom
MC_PC_15018 / / Medical Research Council / United Kingdom
MC_UU_12013/4 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom
G0801418 / / Medical Research Council / United Kingdom
U01 MH094432 / MH / NIMH NIH HHS / United States
MR/L010305/1 / / Medical Research Council / United Kingdom