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

Pourcain, Beaté St; Robinson, Elise; Anttila, Verneri; Sullivan, Bernard; Maller, Julian; Golding, Jean; Skuse, David; Ring, Sue; Evans, David M.; Zammit, Stanley; Fisher, Simon E.; Neale, Benjamin M.; Anney, Richard; Ripke, Stephan; Hollegaard, Mads V.; Werge, Thomas; Ronald, Angelica; Grove, Jakob; Hougaard, David M.; Børglum, Anders D.; Mortensen, Preben Bo; Daly, Mark J.; Smith, George Davey

doi:10.1038/mp.2016.198

Cited by 119 publications

(141 citation statements)

References 54 publications

Supporting

Mentioning

122

Contrasting

Order By: Relevance

“…Another key question is whether the SCDC‐measured traits we observed in adolescent girls are truly autistic in nature, or whether they represent a different type of social impairment, for example, arising from the onset of internalising problems, ADHD or psychosis risk (St Pourcain, Eaves, et al., ; St Pourcain, Robinson et al., ). Several strands of evidence support the notion that the female social variability we observed in adolescence is related to autism.…”

Section: Discussionmentioning

confidence: 97%

The development of autistic social traits across childhood and adolescence in males and females

Mandy¹,

Pellicano

Pourcain

et al. 2018

Child Psychology Psychiatry

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 97%

The development of autistic social traits across childhood and adolescence in males and females

Mandy¹,

Pellicano

Pourcain

et al. 2018

Child Psychology Psychiatry

View full text Add to dashboard Cite

show abstract

“…Here, we extend previous work relating participation and polygenic risk for schizophrenia and autism in ALSPAC 13 , 14 by: (i) investigating polygenic scores for other factors which could influence participation in the ALSPAC mothers and children; (ii) investigating the potential impact of selection bias by comparing associations between genetic factors and measured phenotypes in the largest sample with genetic data and a more selected subsample; and (iii) conducting genome-wide association studies of participation measures.…”

Section: Introductionmentioning

confidence: 90%

Exploring the association of genetic factors with participation in the Avon Longitudinal Study of Parents and Children

Taylor

Jones

Sallis

et al. 2018

International Journal of Epidemiology

193

184

View full text Add to dashboard Cite

BackgroundIt is often assumed that selection (including participation and dropout) does not represent an important source of bias in genetic studies. However, there is little evidence to date on the effect of genetic factors on participation.MethodsUsing data on mothers (N = 7486) and children (N = 7508) from the Avon Longitudinal Study of Parents and Children, we: (i) examined the association of polygenic risk scores for a range of sociodemographic and lifestyle characteristics and health conditions related to continued participation; (ii) investigated whether associations of polygenic scores with body mass index (BMI; derived from self-reported weight and height) and self-reported smoking differed in the largest sample with genetic data and a subsample who participated in a recent follow-up; and (iii) determined the proportion of variation in participation explained by common genetic variants, using genome-wide data.ResultsWe found evidence that polygenic scores for higher education, agreeableness and openness were associated with higher participation; and polygenic scores for smoking initiation, higher BMI, neuroticism, schizophrenia, attention-deficit hyperactivity disorder (ADHD) and depression were associated with lower participation. Associations between the polygenic score for education and self-reported smoking differed between the largest sample with genetic data [odds ratio (OR) for ever smoking per standard deviation (SD) increase in polygenic score: 0.85, 95% confidence interval (CI): 0.81, 0.89} and subsample (OR: 0.96, 95% CI: 0.89, 1.03). In genome-wide analysis, single nucleotide polymorphism based heritability explained 18–32% of variability in participation.ConclusionsGenetic association studies, including Mendelian randomization, can be biased by selection, including loss to follow-up. Genetic risk for dropout should be considered in all analyses of studies with selective participation.

show abstract

“…A number of studies have used a polygenic risk score or similar approaches to show overlap in common genetic variation between schizophrenia and developmental outcomes in the general population, and have shown that alleles which increase risk for schizophrenia also associate with, for example, poorer cognitive function and impaired social and communication difficulties, similar to those seen in people with autism spectrum disorders. While the overlaps are not large, neither are they trivial (genetic correlations between 0.18 and 0.37) and support the involvement of alleles that increase risk for schizophrenia in a wider set of developmental traits.…”

Section: Comparative Genetic Architecture Of Schizophrenia and Other mentioning

confidence: 99%

Schizophrenia and the neurodevelopmental continuum:evidence from genomics

2017

View full text Add to dashboard Cite

The idea that disturbances occurring early in brain development contribute to the pathogenesis of schizophrenia, often referred to as the neurodevelopmental hypothesis, has become widely accepted. Despite this, the disorder is viewed as being distinct nosologically, and by implication pathophysiologically and clinically, from syndromes such as autism spectrum disorders, attention-deficit/hyperactivity disorder (ADHD) and intellectual disability, which typically present in childhood and are grouped together as "neurodevelopmental disorders". An alternative view is that neurodevelopmental disorders, including schizophrenia, rather than being etiologically discrete entities, are better conceptualized as lying on an etiological and neurodevelopmental continuum, with the major clinical syndromes reflecting the severity, timing and predominant pattern of abnormal brain development and resulting functional abnormalities. It has also been suggested that, within the neurodevelopmental continuum, severe mental illnesses occupy a gradient of decreasing neurodevelopmental impairment as follows: intellectual disability, autism spectrum disorders, ADHD, schizophrenia and bipolar disorder. Recent genomic studies have identified large numbers of specific risk DNA changes and offer a direct and robust test of the predictions of the neurodevelopmental continuum model and gradient hypothesis. These findings are reviewed in detail. They not only support the view that schizophrenia is a disorder whose origins lie in disturbances of brain development, but also that it shares genetic risk and pathogenic mechanisms with the early onset neurodevelopmental disorders (intellectual disability, autism spectrum disorders and ADHD). They also support the idea that these disorders lie on a gradient of severity, implying that they differ to some extent quantitatively as well as qualitatively. These findings have important implications for nosology, clinical practice and research.

show abstract

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

Cited by 119 publications

References 54 publications

The development of autistic social traits across childhood and adolescence in males and females

The development of autistic social traits across childhood and adolescence in males and females

Exploring the association of genetic factors with participation in the Avon Longitudinal Study of Parents and Children

Schizophrenia and the neurodevelopmental continuum:evidence from genomics

Contact Info

Product

Resources

About