Dataset Information

Association of Polygenic Risk for Attention-Deficit/Hyperactivity Disorder With Co-occurring Traits and Disorders.

ABSTRACT: BACKGROUND:A recent large-scale mega genome-wide association study identified, for the first time, genetic variants at 12 loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). In this study we use a powerful polygenic approach, with polygenic scores derived from the genome-wide association study, to investigate the etiological overlap between ADHD and frequently co-occurring traits and disorders. METHODS:Polygenic risk scores for ADHD derived from the mega genome-wide association study (20,183 cases and 35,191 control subjects) were computed in a large-scale adult population sample (N = 135,726) recruited by the UK Biobank. Regression analyses were conducted to investigate whether polygenic risk for ADHD is associated with related traits and disorders in this population sample. The effects of sex were investigated via inclusion of an interaction term in the models. RESULTS:Polygenic risk for ADHD significantly and positively predicted body mass index (R2 = .45%; p = 5 × 10-129), neuroticism (R2 = .09%; p = 2 × 10-24), depression (R2 = .11%; p = 2 × 10-13), anxiety (R2 = .06%; p = 3 × 10-4), risk taking (R2 = .12%; p = 9 × 10-25), alcohol intake (R2 = .09%; p = 8 × 10-29), smoking (R2 = .33%; p = 4 × 10-21), alcohol dependency (R2 = .21%; p = 5 × 10-6), and negatively predicted verbal-numerical reasoning (R2 = .38%; p = 5 × 10-36). Polygenic risk scores did not significantly predict schizophrenia or bipolar disorder, although this may be because of the small number of diagnostic cases. We found no interaction effects between polygenic risk for ADHD and sex on any phenotypes. CONCLUSIONS:Our findings suggest that common genetic variation underlying risk for clinically diagnosed ADHD also contributes to higher body mass index, neuroticism, anxiety and depressive disorders, alcohol and nicotine use, risk taking, and lower general cognitive ability in the general population. These findings suggest that the co-occurrence of several traits with ADHD is partly explained by the same common genetic variants.

SUBMITTER: Du Rietz E

PROVIDER: S-EPMC6278881 | biostudies-other | 2018 Jul

REPOSITORIES: biostudies-other

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Association of Polygenic Risk for Attention-Deficit/Hyperactivity Disorder With Co-occurring Traits and Disorders.

Du Rietz Ebba E Coleman Jonathan J Glanville Kylie K Choi Shing Wan SW O'Reilly Paul F PF Kuntsi Jonna J

Biological psychiatry. Cognitive neuroscience and neuroimaging 20171214 7

<h4>Background</h4>A recent large-scale mega genome-wide association study identified, for the first time, genetic variants at 12 loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). In this study we use a powerful polygenic approach, with polygenic scores derived from the genome-wide association study, to investigate the etiological overlap between ADHD and frequently co-occurring traits and disorders.<h4>Methods</h4>Polygenic risk scores for ADHD derived from the ...[more]

PMID: 30047479

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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.

Project description:BackgroundAttention-deficit/hyperactivity disorder (ADHD) is often associated with other neurodevelopmental disorders (NDs) and with risky behaviors and adverse health outcomes, including injuries. Treatment with ADHD medication has been associated with reduced risk of injuries. However, it is unknown whether the association is present in individuals with co-occurring NDs. The aim of the present study was to estimate the association between ADHD medication use and unintentional injuries in Sweden in children and adolescents with ADHD, including those with co-occurring NDs.MethodsUsing a linkage of several national registers via the unique personal identification number, we identified individuals with a diagnosis of ADHD and of other NDs, including autism spectrum disorder, intellectual disability, communication disorders, learning disorders and motor disorders. The primary outcome was unintentional injuries. Secondary outcome was traumatic brain injury (TBI). Individuals were followed from January 1st 2006 or their 5th birthday or the date of the first unintentional injury, whichever came last, to December 31st 2013 or their 18th birthday or death, whichever came first. We compared the rate of injuries during periods on-treatment with the rate of injuries during periods off-treatment within the same individual using stratified Cox regression to calculate hazard ratio (HR) with 95% confidence intervals (CIs).ResultsFor children and adolescents with ADHD (N = 9,421) the rate of any unintentional injuries (HR = 0.85; 95% CI = 0.78-0.92) and TBIs (HR = 0.27; 95% CIs = 0.20-0.38) during medicated periods was lower than during non-medicated periods. Similar results were found among individuals with co-occurring NDs (N = 2,986), for unintentional injuries (HR = 0.88; 95% CI = 0.77-1.01) and for TBIs (HR = 0.27; 95% CI = 0.16-0.44).ConclusionsBeneficial effects of ADHD medication may extend beyond reduction of ADHD core symptoms to prevention of unintentional injuries in children and adolescents, including individuals with co-occurring NDs.

Dataset Information

Association of Polygenic Risk for Attention-Deficit/Hyperactivity Disorder With Co-occurring Traits and Disorders.

Publications

Association of Polygenic Risk for Attention-Deficit/Hyperactivity Disorder With Co-occurring Traits and Disorders.

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