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. 2016 May;48(5):552-5.
doi: 10.1038/ng.3529. Epub 2016 Mar 21.

Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population

Elise B Robinson  1   2   3 , Beate St Pourcain  4   5 , Verneri Anttila  1   2   3 , Jack A Kosmicki  1   2   3   6 , Brendan Bulik-Sullivan  1   2   3 , Jakob Grove  7   8   9   10 , Julian Maller  1   2   3 , Kaitlin E Samocha  1   2   3   11 , Stephan J Sanders  12 , Stephan Ripke  1   2   3   13 , Joanna Martin  1   2   3 , Mads V Hollegaard  14 , Thomas Werge  8   15   16 , David M Hougaard  14 ; iPSYCH-SSI-Broad Autism Group; Benjamin M Neale  1   2   3   17 , David M Evans  4   18 , David Skuse  19 , Preben Bo Mortensen  7   8   20 , Anders D Børglum  7   8   9 , Angelica Ronald  21 , George Davey Smith  4 , Mark J Daly  1   2   3
Collaborators, Affiliations

Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population

Elise B Robinson et al. Nat Genet. 2016 May.

Abstract

Almost all genetic risk factors for autism spectrum disorders (ASDs) can be found in the general population, but the effects of this risk are unclear in people not ascertained for neuropsychiatric symptoms. Using several large ASD consortium and population-based resources (total n > 38,000), we find genome-wide genetic links between ASDs and typical variation in social behavior and adaptive functioning. This finding is evidenced through both LD score correlation and de novo variant analysis, indicating that multiple types of genetic risk for ASDs influence a continuum of behavioral and developmental traits, the severe tail of which can result in diagnosis with an ASD or other neuropsychiatric disorder. A continuum model should inform the design and interpretation of studies of neuropsychiatric disease biology.

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Conflict of interest statement

COI

We have no conflicts of interest to report.

Figures

Figure 1
Figure 1
The genetic correlation between ASDs and pediatric social and communication difficulties in the general population Note: Genetic correlations are shown +/− one standard error; p-values indicate probability with which true genetic correlation is zero; PGC= Psychiatric Genomics Consortium; ASD= Autism Spectrum Disorders; iPSYCH= iPSYCH-SSI-Broad Autism project; SCZ=schizophrenia; MDD=major depressive disorder; BPD= bipolar disorder. Genetic correlations were estimated using constrained intercept LD score correlation. The correlations between PGC-ASD and each of PGC-SCZ, PGC-MDD, and PGC-BPD are modified from Bulik-Sullivan and Finucane et al. (2015).
Figure 2
Figure 2
a. The distribution of Vineland scores overlaps between SSC cases and controls Note: SSC= Simons Simplex Collection. The Vineland Composite Standard Score is normed, across ages, at mean 100, standard deviation (SD) 15 in the general population. The SSC case mean (73.3, SD=12.2) is significantly lower than the SSC control mean (103.0, SD=11.3, p<1e-20). b. De novo variation influences a continuum of functional outcomes in ASD cases and controls Note: Natural (loess) association shown for both cases and controls; p-values derived from poisson regression; LoF= Loss of Function; DCM = probably damaging constrained missense; ExAC= Exome Aggregation Consortium.
Figure 2
Figure 2
a. The distribution of Vineland scores overlaps between SSC cases and controls Note: SSC= Simons Simplex Collection. The Vineland Composite Standard Score is normed, across ages, at mean 100, standard deviation (SD) 15 in the general population. The SSC case mean (73.3, SD=12.2) is significantly lower than the SSC control mean (103.0, SD=11.3, p<1e-20). b. De novo variation influences a continuum of functional outcomes in ASD cases and controls Note: Natural (loess) association shown for both cases and controls; p-values derived from poisson regression; LoF= Loss of Function; DCM = probably damaging constrained missense; ExAC= Exome Aggregation Consortium.
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Comment in

References

    1. Gaugler T, et al. Most genetic risk for autism resides with common variation. Nat Genet. 2014;46:881–885. - PMC - PubMed
    1. Krumm N, et al. Excess of rare, inherited truncating mutations in autism. Nat Genet. 2015;47:582–588. - PMC - PubMed
    1. Lee SH, et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet. 2013;45:984–994. - PMC - PubMed
    1. Bulik-Sullivan BK, et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet. 2015;47:291–295. - PMC - PubMed
    1. De Rubeis S, et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature. 2014;515:209–215. - PMC - PubMed

Online Methods References

    1. Bulik-Sullivan B, et al. An atlas of genetic correlations across human diseases and traits. Nat Genet. 2015;47:1236–1241. - PMC - PubMed
    1. Yang J, Lee SH, Goddard ME, Visscher PM. GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet. 2011;88:76–82. - PMC - PubMed
    1. Loh PR, et al. Contrasting regional architectures of schizophrenia and other complex diseases using fast variance components analysis. 2015 - PMC - PubMed
    1. Boyd A, et al. Cohort Profile: The 'Children of the 90s'--the index offspring of the Avon Longitudinal Study of Parents and Children. Int J Epidemiol. 2012 - PMC - PubMed
    1. Fraser A, et al. Cohort Profile: the Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort. Int J Epidemiol. 2013;42:97–110. - PMC - PubMed

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