Evidence
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
Nat Genet. 2023 Nov 30. doi: 10.1038/s41588-023-01593-7. Online ahead of print.
ABSTRACT
Attention deficit hyperactivity disorder (ADHD) is a complex disorder that manifests variability in long-term outcomes and clinical presentations. The genetic contributions to such heterogeneity are not well understood. Here we show several genetic links to clinical heterogeneity in ADHD in a case-only study of 14,084 diagnosed individuals. First, we identify one genome-wide significant locus by comparing cases with ADHD and autism spectrum disorder (ASD) to cases with ADHD but not ASD. Second, we show that cases with ASD and ADHD, substance use disorder and ADHD, or first diagnosed with ADHD in adulthood have unique polygenic score (PGS) profiles that distinguish them from complementary case subgroups and controls. Finally, a PGS for an ASD diagnosis in ADHD cases predicted cognitive performance in an independent developmental cohort. Our approach uncovered evidence of genetic heterogeneity in ADHD, helping us to understand its etiology and providing a model for studies of other disorders.
PMID:38036780 | DOI:10.1038/s41588-023-01593-7
![Google](https://www.google.com/images/branding/googlelogo/2x/googlelogo_light_color_92x30dp.png)
![Google Keep](https://www.gstatic.com/images/branding/product/1x/keep_48dp.png)
![Share on Linkedin](https://psychiatryai.com/wp-content/uploads/2023/10/linkedin-logo-png-2048-1.png)
Estimated reading time: 3 minute(s)
Latest: Psychiatryai.com #RAISR4D Evidence
![](/wp-content/uploads/2024/04/bd462cc11bcf0bd0d0d6f1d0f8b7cd04-modified-1.png)
Cool Evidence: Engaging Young People and Students in Real-World Evidence
![](/wp-content/uploads/2024/04/bd462cc11bcf0bd0d0d6f1d0f8b7cd04-modified-1.png)
Real-Time Evidence Search [Psychiatry]
![](/wp-content/uploads/2024/04/pubmed.png)
AI Research
![](/wp-content/uploads/2024/05/Il5nR_nf_400x400-modified-1.png)
Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
🌐 90 Days
AI Virtual Reality Related Evidence Matrix
Dissecting the polygenic contribution of attention-deficit/hyperactivity disorder and autism spectrum disorder on school performance by their relationship with educational attainment Associations of polygenic risk scores differentiating attention-deficit hyperactivity disorder from autism spectrum disorder with cognitive and cortical alterations in Schizophrenia patients Associations of polygenic risk scores differentiating attention-deficit hyperactivity disorder from autism spectrum disorder with cognitive and cortical alterations in Schizophrenia patients The role of co-occurring conditions and genetics in the associations of eating disorders with attention-deficit/hyperactivity disorder and autism spectrum disorder The role of co-occurring conditions and genetics in the associations of eating disorders with attention-deficit/hyperactivity disorder and autism spectrum disorder Adult symptoms of ASD in relation to excessive internet use: The roles of ADHD symptoms and negative mood Systematic review and meta-analysis: relative age in attention-deficit/ hyperactivity disorder and autism spectrum disorder Systematic review and meta-analysis: relative age in attention-deficit/ hyperactivity disorder and autism spectrum disorder Association between maternal antidepressant use during pregnancy and the risk of autism spectrum disorder and attention deficit hyperactivity disorder in offspring Objective measurement of movement variability using wearable sensors predicts ASD outcomes in infants at high likelihood for ASD and ADHD Objective measurement of movement variability using wearable sensors predicts ASD outcomes in infants at high likelihood for ASD and ADHD Longitudinal study on all-cause and suicide mortality among individuals with attention deficit hyperactivity disorder Longitudinal study on all-cause and suicide mortality among individuals with attention deficit hyperactivity disorder Longitudinal study on all-cause and suicide mortality among individuals with attention deficit hyperactivity disorder Use of Clonidine in Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder Comorbidity: Report of 3 Cases Do Wechsler intelligence scales predict academic achievement in children with ADHD or autism? A systematic review and meta-analysis Do Wechsler intelligence scales predict academic achievement in children with ADHD or autism? A systematic review and meta-analysis Using polygenic scores in combination with symptom rating scales to identify attention-deficit/hyperactivity disorder Sexually Transmitted Diseases and Attention-Deficit/Hyperactivity Disorder: A Systematic Literature Review Comorbid ADHD and Pediatric Sickle Cell Disease: Prevalence and Risk Factors Adenosinergic System and Nucleoside Transporters in Attention Deficit Hyperactivity Disorder: Current Findings Investigating the increased risk of schizophrenia and bipolar disorders in relatives of ADHD probands using colocalization analysis of common genetic variants Growing evidence of pharmacotherapy effectiveness in managing attention-deficit/hyperactivity disorder in young children with or without autism spectrum disorder: a minireview Attention-deficit/hyperactivity disorder and subsequent diagnoses of major psychiatric disorders: a nationwide population-based study A comparison of visual attention to pictures in the Autism Diagnostic Observation Schedule in children and adolescents with ADHD and/or autism A comparison of visual attention to pictures in the Autism Diagnostic Observation Schedule in children and adolescents with ADHD and/or autism Association of prenatal and postnatal exposure to air pollution with clinically diagnosed attention deficit hyperactivity disorder: a systematic review Social challenges, autism spectrum disorder, and attention deficit/hyperactivity disorder in youth with neurofibromatosis type I Sleep problems and circadian rhythm functioning in autistic children, autism with co-occurring attention deficit hyperactivity disorder, and typically developing children: A comparative study Prevalence and Correlates of Poor Safety Awareness and Accidental Injury in AASD, ADHD, ASD + ADHD, and Neurotypical Youth Samples Exploring Neuroimaging Association Scores in adulthood ADHD and middle-age trajectories Links Among Attention-Deficit/Hyperactivity Disorder Symptoms and Psycholinguistic Abilities Are Different for Children With and Without Developmental Language Disorder Decreased gray matter volume in the anterior cerebellar of attention deficit/hyperactivity disorder comorbid oppositional defiant disorder children with associated cerebellar-cerebral hyperconnectivity: insights from a combined structural MRI… Risk of Neurodevelopmental Disorders in Offspring of Parents with Major Depressive Disorder: A Birth Cohort Study The symptomatology of Attention-Deficit/Hyperactivity Disorder and the genetic control of vitamin D levels Incremental Validity of Trait Impulsivity, Dysfunctional Emotional Regulation, and Affect Lability in the Predictions of Attention Deficit Hyperactivity Disorder and Oppositional Defiant Disorder Symptoms in Adults "I Found Comfort in Exercising": Exploring Experiences With Exercise for Adults With Attention-Deficit/Hyperactivity Disorder "I Found Comfort in Exercising": Exploring Experiences With Exercise for Adults With Attention-Deficit/Hyperactivity Disorder Insomnia Polygenic Component on Attention Deficit-Hyperactivity Disorder: Exploring this Association Using Genomic Data from Brazilian Families Main focus of parents of children with attention deficit hyperactivity disorder and the effectiveness of early clinical screening Gene - maltreatment interplay in adult ADHD symptoms: main role of a gene-environment correlation effect in a Brazilian population longitudinal study Sex differences in attention-deficit hyperactivity disorder diagnosis and clinical care: a national study of population healthcare records in Wales Prospective and Cross-Sectional Factors Predicting Caregiver Motivation to Vaccinate Children with Attention-Deficit/Hyperactivity Disorder against COVID-19: A Follow-Up Study Prospective and Cross-Sectional Factors Predicting Caregiver Motivation to Vaccinate Children with Attention-Deficit/Hyperactivity Disorder against COVID-19: A Follow-Up Study Attention-deficit/hyperactivity disorder (ADHD) in cultural context II: a comparison of the links between ADHD symptoms and waiting-related responses in Hong Kong and UK Method for Testing Etiologic Heterogeneity Among Non-Competing Diagnoses, Applied to Impact of Perinatal Exposures on Autism and Attention Deficit Hyperactivity Disorder Vitamins B(9) and B(12) in children with attention deficit hyperactivity disorder (ADHD) The Development and Content Validation of a Clinical Screening Scale to Identify Attention-Deficit Hyperactivity Disorder Cases Based on the Gender Perspective: An e-Delphi Study Cognitive disengagement syndrome and attention deficit hyperactivity disorder: An examination of relationships with alexithymia and emotion regulation difficulties Use of Citicoline in Attention-Deficit/Hyperactivity Disorder: A Pilot Study Proteome-wide association studies have predicted that the protein abundance of LSM6, GMPPB, ICA1L, and CISD2 is associated with attention-deficit/hyperactivity disorder Proteome-wide association studies have predicted that the protein abundance of LSM6, GMPPB, ICA1L, and CISD2 is associated with attention-deficit/hyperactivity disorder Push-Pull Mechanism of Attention and Emotion in Children with Attention Deficit Hyperactivity Disorder "Your Child Should Not Return": Preschool Expulsion Among Children With Attention-Deficit/Hyperactivity Disorder as an Early Indicator of Later Risks Prisoners with Attention Deficit Hyperactivity Disorder: co-morbidities and service pathways The influence of COVID-19 on attention-deficit/hyperactivity disorder diagnosis and treatment rates across age, gender, and socioeconomic status: A 20-year national cohort study Antibiotic use and risk of autism spectrum disorder and attention-deficit/hyperactivity disorder: a population-based cohort study Pre-attentive and Attentive Auditory Event-related Potentials in Children With Attention-Deficit Hyperactivity Disorder and Autism Characterizing Genetic Pathways Unique to Autism Spectrum Disorder at Multiple Levels of Biological Analysis Cognitive Correlates of Risky Decision-Making in Individuals with and without ADHD: A Meta-analysis Distinct structural brain network properties in children with familial versus non-familial attention-deficit/hyperactivity disorder (ADHD) Similarities and differences of neuropsychological functions, metacognitive abilities and resilience in Cognitive Disengagement Syndrome (CDS) and Attention Deficit/Hyperactivity Disorder (ADHD) Global Sensory Features are Linked to Executive and Attentional Impairments in Autism Spectrum Disorders Clinical and genetic characteristics of a child with Sotos syndrome and attention-deficit/hyperactivity disorder: A case report
Evidence Blueprint
Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
☊ AI-Driven Related Evidence Nodes
(recent articles with at least 5 words in title)
More Evidence
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder
🌐 365 Days
AI Virtual Reality Related Evidence Matrix
Dissecting the polygenic contribution of attention-deficit/hyperactivity disorder and autism spectrum disorder on school performance by their relationship with educational attainment Causal association of attention-deficit/hyperactivity disorder and autism spectrum disorder with post-traumatic stress disorder Sleep in Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder Evaluation and Management of Attention-Deficit/ Hyperactivity Disorder (ADHD) in Children and Adolescents Autistic spectrum disorders, attention deficit disorders, hyperactivity and emotional dysregulation: masking and approach Associations of polygenic risk scores differentiating attention-deficit hyperactivity disorder from autism spectrum disorder with cognitive and cortical alterations in Schizophrenia patients Associations of polygenic risk scores differentiating attention-deficit hyperactivity disorder from autism spectrum disorder with cognitive and cortical alterations in Schizophrenia patients Prevalence of comorbidity of autism and ADHD and associated characteristics in school population: EPINED study The role of co-occurring conditions and genetics in the associations of eating disorders with attention-deficit/hyperactivity disorder and autism spectrum disorder The role of co-occurring conditions and genetics in the associations of eating disorders with attention-deficit/hyperactivity disorder and autism spectrum disorder Paraphilic fantasies and behavior in attention deficit/hyperactivity disorder and their association with hypersexuality Adult symptoms of ASD in relation to excessive internet use: The roles of ADHD symptoms and negative mood Systematic review and meta-analysis: relative age in attention-deficit/ hyperactivity disorder and autism spectrum disorder Systematic review and meta-analysis: relative age in attention-deficit/ hyperactivity disorder and autism spectrum disorder What is adult ADHD after all? Quality of Life Among Caregivers of Children with Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder: A Cross Sectional Study Motor proficiency of persons with attention deficit hyperactivity disorder or autism spectrum disorder diagnosed in adulthood Variations in Anxiety and Related Psychiatric Comorbidity Levels Among Youths With Individual Diagnoses of Autism Spectrum Disorder or Attention Deficit Hyperactivity Disorder and Those With Both Diagnoses Motor proficiency of persons with attention deficit hyperactivity disorder or autism spectrum disorder diagnosed in adulthood Profiling Autism and Attention Deficit Hyperactivity Disorder Traits in Children with SYNGAP1-Related Intellectual Disability A Nomogram for Predicting ADHD and ASD in Child and Adolescent Mental Health Services (CAMHS) Attention-deficit/hyperactivity disorder Symptoms of ADHD and Autism Spectrum Disorder Interactively Predict Children's Verbal Fluency Substance Use Disorder in Adults with ADHD in South Dakota Management of sleep disorders in autism spectrum disorder with co-occurring attention-deficit hyperactivity disorder: update for clinicians Association between maternal antidepressant use during pregnancy and the risk of autism spectrum disorder and attention deficit hyperactivity disorder in offspring Objective measurement of movement variability using wearable sensors predicts ASD outcomes in infants at high likelihood for ASD and ADHD Objective measurement of movement variability using wearable sensors predicts ASD outcomes in infants at high likelihood for ASD and ADHD A comparative study on dietary diversity and gut microbial diversity in children with autism spectrum disorder, attention-deficit hyperactivity disorder, their neurotypical siblings, and non-related neurotypical volunteers: a cross-sectional study Are We Measuring ADHD or Anxiety? Examining the Factor Structure and Discriminant Validity of the Adult ADHD Self-Report Scale in an Adult Anxiety Disorder Population Rare X-linked variants carry predominantly male risk in autism, Tourette syndrome, and ADHD Longitudinal study on all-cause and suicide mortality among individuals with attention deficit hyperactivity disorder Longitudinal study on all-cause and suicide mortality among individuals with attention deficit hyperactivity disorder Longitudinal study on all-cause and suicide mortality among individuals with attention deficit hyperactivity disorder Risky driving behavior among individuals with Autism, ADHD, and typically developing persons Use of Clonidine in Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder Comorbidity: Report of 3 Cases ASD and ADHD: Divergent activating patterns of prefrontal cortex in executive function tasks? The Association between Threatened Miscarriage and Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder in Offspring by Age 14 Years Parenting Stress in Autistic and ADHD Children: Implications of Social Support and Child Characteristics Attention-deficit hyperactivity disorder medication use is associated with testosterone hypofunction-results from a national claims database analysis Do Wechsler intelligence scales predict academic achievement in children with ADHD or autism? A systematic review and meta-analysis Do Wechsler intelligence scales predict academic achievement in children with ADHD or autism? A systematic review and meta-analysis Adult Symptoms of ASD and ADHD in Relation to Alcohol Use: Potential Roles of Transdiagnostic Features Determining cutoff scores on the Conners' adult ADHD rating scales that can definitively rule out the presence of ADHD in a clinical sample Polygenic risk for major depression, attention deficit hyperactivity disorder, neuroticism, and schizophrenia are correlated with experience of intimate partner violence Reducing Risk in the Treatment of Attention-Deficit/Hyperactivity Disorder Among Adults With Comorbidities Comorbidity of autism spectrum and attention deficit/hyperactivity disorder symptoms and their associations with 1-year mental health outcomes in adolescents and young adults Attention Deficit Hyperactivity Disorder (ADHD) Causes and Diagnosis in Adults: A Review Using polygenic scores in combination with symptom rating scales to identify attention-deficit/hyperactivity disorder Word-Finding Difficulties as a Prominent Early Finding in a Later Diagnosis of Attention Deficit Hyperactivity Disorder Sexually Transmitted Diseases and Attention-Deficit/Hyperactivity Disorder: A Systematic Literature Review Assessment of ADHD Subtypes Using Motion Tracking Recognition Based on Stroop Color-Word Tests Novel pharmacological targets for GABAergic dysfunction in ADHD Comorbid ADHD and Pediatric Sickle Cell Disease: Prevalence and Risk Factors The emerging evidence on the association between symptoms of ADHD and gaming disorder: A systematic review and meta-analysis Autism and attention-deficit/hyperactivity disorder in children with Dravet syndrome: A population-based study Language Skills in Children with Attention Deficit Hyperactivity Disorder and Developmental Language Disorder: A Systematic Review Adenosinergic System and Nucleoside Transporters in Attention Deficit Hyperactivity Disorder: Current Findings Social Functioning in Children and Adolescents with ADHD and Autism Spectrum Disorder: A Cross-Disorder Comparison Associations between ADHD and risk of six psychiatric disorders: a Mendelian randomization study Investigating the increased risk of schizophrenia and bipolar disorders in relatives of ADHD probands using colocalization analysis of common genetic variants Assessment of Diagnosis Timing of Attention-Deficit/Hyperactivity Disorder in Working-Age Workers with Psychiatric Diseases Using Large Claims Data Growing evidence of pharmacotherapy effectiveness in managing attention-deficit/hyperactivity disorder in young children with or without autism spectrum disorder: a minireview Attention-deficit/hyperactivity disorder and subsequent diagnoses of major psychiatric disorders: a nationwide population-based study