title: Common polygenic risk for autism spectrum disorder (ASD) is associated with cognitive ability in the general population.
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.
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: T-K
authors.initials: TK
authors.lastname: Clarke
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: M K
authors.initials: MK
authors.lastname: Lupton
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Fernandez-Pujals
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: J
authors.initials: J
authors.lastname: Starr
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: G
authors.initials: G
authors.lastname: Davies
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: S
authors.initials: S
authors.lastname: Cox
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: A
authors.initials: A
authors.lastname: Pattie
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: D C
authors.initials: DC
authors.lastname: Liewald
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: L S
authors.initials: LS
authors.lastname: Hall
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: MacIntyre
authors.affiliation: Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: B H
authors.initials: BH
authors.lastname: Smith
authors.affiliation: Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Hocking
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: S
authors.initials: S
authors.lastname: Padmanabhan
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.|Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.|Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: P A
authors.initials: PA
authors.lastname: Thomson
authors.affiliation: Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.|MRC Human Genetics, MRC IGMM, University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: C
authors.initials: C
authors.lastname: Hayward
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: N K
authors.initials: NK
authors.lastname: Hansell
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: G W
authors.initials: GW
authors.lastname: Montgomery
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: S E
authors.initials: SE
authors.lastname: Medland
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: N G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Wright
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.|Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.|Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.|MRC Human Genetics, MRC IGMM, University of Edinburgh, Edinburgh, Scotland, UK.|Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Porteous
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.|Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.|Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.|MRC Human Genetics, MRC IGMM, University of Edinburgh, Edinburgh, Scotland, UK.|Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: I J
authors.initials: IJ
authors.lastname: Deary
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.|Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: McIntosh
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology* / Q000235:genetics; D000067877:Autism Spectrum Disorder / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D003072:Cognition Disorders / Q000209:etiology*; D015331:Cohort Studies; D016208:Databases, Factual / Q000706:statistics & numerical data; D005192:Family Health; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007361:Intelligence Tests; D016014:Linear Models; D008297:Male; D020412:Multifactorial Inheritance / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012606:Scotland; D012720:Severity of Illness Index; D055815:Young Adult