Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Mar;21(3):419-25.
doi: 10.1038/mp.2015.12. Epub 2015 Mar 10.

Common polygenic risk for autism spectrum disorder (ASD) is associated with cognitive ability in the general population

T-K Clarke  1 , M K Lupton  2 , A M Fernandez-Pujals  1 , J Starr  3 , G Davies  3 , S Cox  3 , A Pattie  3 , D C Liewald  3 , L S Hall  1 , D J MacIntyre  1 , B H Smith  4 , L J Hocking  4 , S Padmanabhan  5 , P A Thomson  3   4   5   6 , C Hayward  6   7 , N K Hansell  2 , G W Montgomery  2 , S E Medland  2 , N G Martin  2 , M J Wright  2 , D J Porteous  3   4   5   6   7   8 , I J Deary  3   4   5   6   7   8   9 , A M McIntosh  1   3
Affiliations

Common polygenic risk for autism spectrum disorder (ASD) is associated with cognitive ability in the general population

T-K Clarke et al. Mol Psychiatry. 2016 Mar.

Abstract

Cognitive impairment is common among individuals diagnosed with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). It has been suggested that some aspects of intelligence are preserved or even superior in people with ASD compared with controls, but consistent evidence is lacking. Few studies have examined the genetic overlap between cognitive ability and ASD/ADHD. The aim of this study was to examine the polygenic overlap between ASD/ADHD and cognitive ability in individuals from the general population. Polygenic risk for ADHD and ASD was calculated from genome-wide association studies of ASD and ADHD conducted by the Psychiatric Genetics Consortium. Risk scores were created in three independent cohorts: Generation Scotland Scottish Family Health Study (GS:SFHS) (n=9863), the Lothian Birth Cohorts 1936 and 1921 (n=1522), and the Brisbane Adolescent Twin Sample (BATS) (n=921). We report that polygenic risk for ASD is positively correlated with general cognitive ability (beta=0.07, P=6 × 10(-7), r(2)=0.003), logical memory and verbal intelligence in GS:SFHS. This was replicated in BATS as a positive association with full-scale intelligent quotient (IQ) (beta=0.07, P=0.03, r(2)=0.005). We did not find consistent evidence that polygenic risk for ADHD was associated with cognitive function; however, a negative correlation with IQ at age 11 years (beta=-0.08, Z=-3.3, P=0.001) was observed in the Lothian Birth Cohorts. These findings are in individuals from the general population, suggesting that the relationship between genetic risk for ASD and intelligence is partly independent of clinical state. These data suggest that common genetic variation relevant for ASD influences general cognitive ability.

PubMed Disclaimer

Conflict of interest statement

AMM has received financial support from Pfizer (formerly Wyeth), Janssen and Lilly. AMM has done consultancy work for Roche Pharmaceuticals. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Proportion of variance explained in cognitive test performance explained by autism spectrum disorder polygenic risk score derived using five different P-value thresholds in the Generation Scotland: Scottish Family Health Study (GS:SFHS). Only tests significantly associated with polygenic risk score are presented. LM, logical memory; MHV, Mill Hill vocabulary; VF, verbal fluency.
Figure 2
Figure 2
Forest plot showing effect size of polygenic risk for autism on general cognitive ability in the Generation Scotland Scottish Family Health Study (GS:SFHS), Lothian Birth Cohort (LBC; LBC1936 and LBC1921) and full-scale IQ in Brisbane Adolescent Twin Sample (BATS). CI, confidence interval; seTE, standard errors; TE, treatment effect (standardized regression coefficients); W(fixed), weight of individual studies in fixed-effect meta-analysis.
See this image and copyright information in PMC

References

    1. 1Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 2011; 68: 1095–1102. - PMC - PubMed
    1. 2Larsson H, Dilshad R, Lichtenstein P, Barker ED. Developmental trajectories of DSM-IV symptoms of attention-deficit/hyperactivity disorder: genetic effects, family risk and associated psychopathology. J Child Psychol Psychiatry 2011; 52: 954–963. - PubMed
    1. 3Lichtenstein P, Carlstrom E, Rastam M, Gillberg C, Anckarsater H. The genetics of autism spectrum disorders and related neuropsychiatric disorders in childhood. Am J Psychiatry 2010; 167: 1357–1363. - PubMed
    1. 4Sherman DK, McGue MK, Iacono WG. Twin concordance for attention deficit hyperactivity disorder: a comparison of teachers' and mothers' reports. Am J Psychiatry 1997; 154: 532–535. - PubMed
    1. 5Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet 2013; 45: 984–994. - PMC - PubMed

Publication types

MeSH terms