Common polygenic risk for autism spectrum disorder (ASD) is associated with cognitive ability in the general population
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 evidenc...
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Published in | Molecular psychiatry Vol. 21; no. 3; pp. 419 - 425 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.03.2016
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
ISSN | 1359-4184 1476-5578 1476-5578 |
DOI | 10.1038/mp.2015.12 |
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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. |
---|---|
AbstractList | 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 super(-7), r super(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 super(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. 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. 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.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. 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 x [10.sup.-7], [r.sup.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.sup.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. 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 x [10.sup.-7], [r.sup.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.sup.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. Molecular Psychiatry (2016) 21, 419-425; doi: 10.1038/mp.2015.12; published online 10 March 2015 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 , r2 =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, r2 =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. 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. |
Audience | Academic |
Author | Starr, J Thomson, P A Smith, B H Hocking, L J Deary, I J McIntosh, A M Fernandez-Pujals, A M Lupton, M K Hall, L S Pattie, A Liewald, D C Clarke, T-K MacIntyre, D J Wright, M J Medland, S E Hayward, C Hansell, N K Padmanabhan, S Martin, N G Davies, G Porteous, D J Cox, S Montgomery, G W |
Author_xml | – sequence: 1 givenname: T-K surname: Clarke fullname: Clarke, T-K email: toni.clarke@ed.ac.uk organization: Division of Psychiatry, University of Edinburgh – sequence: 2 givenname: M K surname: Lupton fullname: Lupton, M K organization: QIMR Berghofer Medical Research Institute – sequence: 3 givenname: A M surname: Fernandez-Pujals fullname: Fernandez-Pujals, A M organization: Division of Psychiatry, University of Edinburgh – sequence: 4 givenname: J surname: Starr fullname: Starr, J organization: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh – sequence: 5 givenname: G surname: Davies fullname: Davies, G organization: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh – sequence: 6 givenname: S surname: Cox fullname: Cox, S organization: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh – sequence: 7 givenname: A surname: Pattie fullname: Pattie, A organization: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh – sequence: 8 givenname: D C surname: Liewald fullname: Liewald, D C organization: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh – sequence: 9 givenname: L S surname: Hall fullname: Hall, L S organization: Division of Psychiatry, University of Edinburgh – sequence: 10 givenname: D J surname: MacIntyre fullname: MacIntyre, D J organization: Division of Psychiatry, University of Edinburgh – sequence: 11 givenname: B H surname: Smith fullname: Smith, B H organization: Division of Applied Health Sciences, University of Aberdeen – sequence: 12 givenname: L J surname: Hocking fullname: Hocking, L J organization: Division of Applied Health Sciences, University of Aberdeen – sequence: 13 givenname: S surname: Padmanabhan fullname: Padmanabhan, S organization: Institute of Cardiovascular and Medical Sciences, University of Glasgow – sequence: 14 givenname: P A surname: Thomson fullname: Thomson, P A organization: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Division of Applied Health Sciences, University of Aberdeen, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh – sequence: 15 givenname: C surname: Hayward fullname: Hayward, C organization: Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, MRC Human Genetics, MRC IGMM, University of Edinburgh – sequence: 16 givenname: N K surname: Hansell fullname: Hansell, N K organization: QIMR Berghofer Medical Research Institute – sequence: 17 givenname: G W surname: Montgomery fullname: Montgomery, G W organization: QIMR Berghofer Medical Research Institute – sequence: 18 givenname: S E surname: Medland fullname: Medland, S E organization: QIMR Berghofer Medical Research Institute – sequence: 19 givenname: N G surname: Martin fullname: Martin, N G organization: QIMR Berghofer Medical Research Institute – sequence: 20 givenname: M J surname: Wright fullname: Wright, M J organization: QIMR Berghofer Medical Research Institute – sequence: 21 givenname: D J surname: Porteous fullname: Porteous, D J organization: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Division of Applied Health Sciences, University of Aberdeen, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, MRC Human Genetics, MRC IGMM, University of Edinburgh, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital – sequence: 22 givenname: I J surname: Deary fullname: Deary, I J organization: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Division of Applied Health Sciences, University of Aberdeen, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, MRC Human Genetics, MRC IGMM, University of Edinburgh, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Department of Psychology, University of Edinburgh – sequence: 23 givenname: A M surname: McIntosh fullname: McIntosh, A M organization: Division of Psychiatry, University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25754080$$D View this record in MEDLINE/PubMed |
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Title | Common polygenic risk for autism spectrum disorder (ASD) is associated with cognitive ability in the general population |
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