Dataset Information

Genetic risk for attention-deficit/hyperactivity disorder contributes to neurodevelopmental traits in the general population.

ABSTRACT:

Background

Attention-deficit/hyperactivity disorder (ADHD) can be viewed as the extreme end of traits in the general population. Epidemiological and twin studies suggest that ADHD frequently co-occurs with and shares genetic susceptibility with autism spectrum disorder (ASD) and ASD-related traits. The aims of this study were to determine whether a composite of common molecular genetic variants, previously found to be associated with clinically diagnosed ADHD, predicts ADHD and ASD-related traits in the general population.

Methods

Polygenic risk scores were calculated in the Avon Longitudinal Study of Parents and Children (ALSPAC) population sample (N = 8229) based on a discovery case-control genome-wide association study of childhood ADHD. Regression analyses were used to assess whether polygenic scores predicted ADHD traits and ASD-related measures (pragmatic language abilities and social cognition) in the ALSPAC sample. Polygenic scores were also compared in boys and girls endorsing any (rating ? 1) ADHD item (n = 3623).

Results

Polygenic risk for ADHD showed a positive association with ADHD traits (hyperactive-impulsive, p = .0039; inattentive, p = .037). Polygenic risk for ADHD was also negatively associated with pragmatic language abilities (p = .037) but not with social cognition (p = .43). In children with a rating ? 1 for ADHD traits, girls had a higher polygenic score than boys (p = .003).

Conclusions

These findings provide molecular genetic evidence that risk alleles for the categorical disorder of ADHD influence hyperactive-impulsive and attentional traits in the general population. The results further suggest that common genetic variation that contributes to ADHD diagnosis may also influence ASD-related traits, which at their extreme are a characteristic feature of ASD.

SUBMITTER: Martin J

PROVIDER: S-EPMC4183378 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Publications

Genetic risk for attention-deficit/hyperactivity disorder contributes to neurodevelopmental traits in the general population.

Martin Joanna J Hamshere Marian L ML Stergiakouli Evangelia E O'Donovan Michael C MC Thapar Anita A

Biological psychiatry 20140225 8

<h4>Background</h4>Attention-deficit/hyperactivity disorder (ADHD) can be viewed as the extreme end of traits in the general population. Epidemiological and twin studies suggest that ADHD frequently co-occurs with and shares genetic susceptibility with autism spectrum disorder (ASD) and ASD-related traits. The aims of this study were to determine whether a composite of common molecular genetic variants, previously found to be associated with clinically diagnosed ADHD, predicts ADHD and ASD-relat ...[more]

PMID: 24673882

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Project description:ImportanceAttention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder that shows clinical and genetic overlap with other childhood neurodevelopmental disorders. Levels of ADHD symptoms typically decline across childhood and adolescence, although they remain elevated for some individuals. The determinants of symptom persistence and decline are not yet fully understood.ObjectivesTo test the hypothesis that genetic risk variant load for ADHD (indexed by polygenic risk scores [PRS]), but not for other psychiatric disorders, is associated with population-based ADHD symptom trajectories across childhood and adolescence, and to examine whether higher genetic liability for ADHD is correlated with total number of additional neurodevelopmental disorders (multimorbidity) in childhood.Design, setting, and participantsThe Avon Longitudinal Study of Parents and Children, an ongoing prospective population-based cohort study, has been collecting data on 14 701 children, including 9757 with data on symptoms of ADHD at multiple time points, since September 6, 1990. The primary exposure variables, PRS, were generated using results of a genome-wide association study from the Psychiatric Genomics Consortium. Childhood multimorbidity scores (ages 7-9 years) were measured by total impairments in 4 domains known to share genetic liability with ADHD: IQ, social communication, pragmatic language, and conduct. Data analysis was conducted from March 1 to September 8, 2016.Main outcomes and measuresAttention-deficit/hyperactivity disorder symptom trajectories from ages 4 to 17 years (7 time points).ResultsAmong 9757 children with data on symptoms of ADHD at multiple time points (age range, 4-17 years; 4968 boys and 4789 girls), 4 ADHD symptom trajectories were identified: low (82.6%), intermediate (7.7%), childhood-limited (5.8%), and persistent (3.9%). Mean (SE) PRS for ADHD were higher in children in the persistent trajectory (0.254 [0.069]) compared with each of the other 3 trajectories (low, -0.018 [0.014], χ21 = 14.67, P < .001, odds ratio, 1.31; intermediate, 0.054 [0.055], χ21 = 4.70, P = .03, odds ratio, 1.22; and childhood-limited, 0.017 [0.060], χ21 = 6.50, P = .01, odds ratio, 1.27). Findings were specific to PRS for ADHD; PRS for other psychiatric conditions did not differ across trajectories. The proportion of children with multimorbidity was also highest in those in the persistent trajectory (42.5%; 95% CI, 33.9%-51.1%; P < .001) and was associated with persistence of ADHD symptoms independent of PRS.Conclusions and relevancePersistence of ADHD symptoms across childhood and adolescence in the general population is associated with higher PRS for ADHD. Childhood multimorbidity was also associated with persistence of ADHD symptoms and may help to identify children with ADHD whose symptoms are most likely to continue into adolescence.

Project description:BackgroundAttention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are generally considered early-onset disorders so most research has therefore tended to focus on children. Differences between ADHD/ASD in adult life and childhood have been noted, but few population-based studies have examined them in adulthood. Furthermore, the interpretation of findings is hampered by changes in measure and from parent report to self-report.MethodWe examined continuous/trait measures of parent- and self-rated ADHD and ASD in adulthood (age 25 years) in a UK prospective longitudinal sample ALPSAC (the Avon Longitudinal Study of Parents and Children), using many of the same measures that parents reported on in childhood (N = 6,064). Our aim was to investigate these traits in this population for mean-level sex differences, overlaps with other cognitive, learning and communication problems and their associations with polygenic risk scores (PRS) for neuropsychiatric disorders (ADHD, ASD, schizophrenia, depression and anxiety).ResultsADHD and ASD traits in adulthood, as in childhood, showed associations with childhood cognitive, learning and communication problems and adult communication/language measures, although less so for self-ratings than parent-ratings. Males had higher ADHD and ASD trait levels, but this was not as marked as in childhood. In adulthood, ADHD (both parent- and self-rated) and ASD (parent-rated) symptoms showed associations with ADHD PRS; self-reported ADHD also showed association with depression PRS, whereas self-reported ASD did not show strong PRS associations.ConclusionsOur findings suggest that in young adults, ADHD and ASD symptoms have similar characteristics as they do in childhood. Associations with other cognitive, learning and communication problems, and ADHD PRS were somewhat less pronounced for self-reported adult ADHD and ASD symptoms, suggesting that even at age 25, parent reports, where available, could be clinically useful.

Project description:BackgroundThe genetic architecture of ADHD is complex, with rare and common variants involved. Common genetic variants (as indexed by a composite risk score) associated with clinical ADHD significantly predict ADHD and autistic-like behavioural traits in children from the general population, suggesting that ADHD lies at the extreme of normal trait variation. ADHD and other neurodevelopmental disorders share neurocognitive difficulties in several domains (e.g. impaired cognitive ability and executive functions). We hypothesised that ADHD composite genetic risk scores derived from clinical ADHD cases would also contribute to variation in neurocognitive abilities in the general population.MethodsChildren (N = 6,832) from a UK population cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), underwent neurocognitive testing. Parent-reported measures of their children's ADHD and autistic-like traits were used to construct a behavioural latent variable of 'neurodevelopmental traits'. Composite genetic risk scores for ADHD were calculated for ALSPAC children based on findings from an independent ADHD case-control genome-wide association study. Structural equation modelling was used to assess associations between ADHD composite genetic risk scores and IQ, working memory, inhibitory control and facial emotion recognition, as well as the latent 'neurodevelopmental trait' measure.ResultsThe results confirmed that neurocognitive and neurodevelopmental traits are correlated in children in the general population. Composite genetic risk scores for ADHD were independently associated with lower IQ (β = -.05, p < .001) and working memory performance (β = -.034, p = .013), even after accounting for the relationship with latent neurodevelopmental behavioural trait scores. No associations were found between composite genetic risk scores and inhibitory control or emotion recognition (p > .05).ConclusionsThese findings suggest that common genetic variants relevant to clinically diagnosed ADHD have pleiotropic effects on neurocognitive traits as well as behavioural dimensions in the general population. This further suggests that the well-recognised association between cognition and neurodevelopmental behavioural traits is underpinned at a biological level.

Project description:Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD) are two of the most represented neurodevelopmental conditions in childhood. The diagnostic shift introduced by the DSM-5, allowing a combined diagnosis of ADHD and ASD, poses different clinical challenges related to diagnostic overshadowing, accuracy of clinical judgment and potential delay in an ASD diagnosis in children presenting with ADHD. Here we tried to disentangle the clinical phenotype and specificity of the two co-occurring conditions in relation to autism traits and empathy, by comparing children with ASD with and without comorbid ADHD with children presenting ADHD only and children with typical development. The child versions of the Autism Quotient (C-AQ) and Empathy Quotient (C-EQ) were administered to a total sample of 198 male children between 6 and 14 years old with age appropriate language skills and normal intelligence. Univariate analysis demonstrated no significant differences in the C-AQ total and subscale scores as well as the C-EQ between children with ASD and children with ASD + ADHD, while children with ADHD alone presented an intermediate phenotype between ASD and TD. Furthermore, a receiver operating characteristic (ROC) analysis was applied to discriminate among the different phenotypes. We found that the C-AQ and C-EQ were accurate at distinguishing with satisfactory reliability between: (a) ASD vs. non- ASD (N-ASD) groups comprising both ADHD and TD children (Area Under the Curve AUC 88% for C-AQ and 81% for C-EQ); (b) ASD and TD (AUC 92% for C-AQ and 95% for C-EQ); (c) ASD and ADHD (AUC 80% for C-AQ and 68% for C-EQ). Our data confirm the reliability of the C-AQ and C-EQ as behavioral markers to differentiate ASD (regardless of comorbid ADHD) from an ADHD condition and TD. Interestingly, in our sample an ADHD condition does not increase the severity of the clinical phenotype in terms of autism traits distribution and empathy, suggesting that the psychological measures detected by the two quantitative instruments are independent of ADHD traits. This evidence will contribute to the translational efforts in developing better tailored treatments and preventive strategies.

Dataset Information

Genetic risk for attention-deficit/hyperactivity disorder contributes to neurodevelopmental traits in the general population.

Background

Methods

Results

Conclusions

Publications

Genetic risk for attention-deficit/hyperactivity disorder contributes to neurodevelopmental traits in the general population.

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