Genome-Wide Analysis of Copy Number Variants in Attention Deficit Hyperactivity Disorder: The Role of Rare Variants and Duplications at 15q13.3
Copyright policy )Genome-Wide Analysis of Copy Number Variants in Attention Deficit Hyperactivity Disorder: The Role of Rare Variants and Duplications at 15q13.3
Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Because of its multifactorial etiology, however, identifying the genes involved has been difficult. The authors followed up on recent findings suggesting that rare copy number variants (CNVs) may be important for ADHD etiology.The authors performed a genome-wide analysis of large, rare CNVs (100 kb in size, which segregated into 912 independent loci. Overall, the rate of rare CNVs >100 kb was 1.15 times higher in ADHD case subjects relative to comparison subjects, with duplications spanning known genes showing a 1.2-fold enrichment. In accordance with a previous study, rare CNVs >500 kb showed the greatest enrichment (1.28-fold). CNVs identified in ADHD case subjects were significantly enriched for loci implicated in autism and in schizophrenia. Duplications spanning the CHRNA7 gene at chromosome 15q13.3 were associated with ADHD in single-locus analysis. This finding was consistently replicated in an additional 2,242 ADHD case subjects and 8,552 comparison subjects from four independent cohorts from the United Kingdom, the United States, and Canada. Presence of the duplication at 15q13.3 appeared to be associated with comorbid conduct disorder.These findings support the enrichment of large, rare CNVs in ADHD and implicate duplications at 15q13.3 as a novel risk factor for ADHD. With a frequency of 0.6% in the populations investigated and a relatively large effect size (odds ratio=2.22, 95% confidence interval=1.5–3.6), this locus could be an important contributor to ADHD etiology.
- Cardiff University United Kingdom
- Aalborg University Denmark
- State University of New York at Potsdam United States
- University of Queensland Australia
- University of Massachusetts System United States
alpha7 Nicotinic Acetylcholine Receptor, 150, Gene Dosage, Inheritance Patterns, Social Sciences, Psychiatry and Psychology, ASSOCIATION SCAN, DCN PAC - Perception action and control, *Attention Deficit Disorder with Hyperactivity, Receptors, Nicotinic, Nicotinic, NCMLS 6: Genetics and epigenetic pathways of disease, Medical and Health Sciences, MOLECULAR-GENETICS, Segmental Duplications, Genomic, SCHIZOPHRENIA, Receptors, 2.1 Biological and endogenous factors, Aetiology, Child, CHROMOSOMAL DELETIONS, In Situ Hybridization, In Situ Hybridization, Fluorescence, Pediatric, Psychiatry, Great Britain, Single Nucleotide, New Research, Serious Mental Illness, Segmental Duplications, Causality, Mental Health, Child, Preschool, Genes & Society, Female, DCN PAC - Perception action and control IGMD 3: Genomic disorders and inherited multi-system disorders, CANDIDATE GENE, 570, *Gene Dosage, Canada, Adolescent, DCN MP - Plasticity and memory, NCEBP 9: Mental health, 610, MICRODUPLICATIONS, Polymorphism, Single Nucleotide, Fluorescence, Clinical Research, 2738 Psychiatry and Mental health, 616, Genetics, ADHD, Humans, Genetic Predisposition to Disease, DCN PAC - Perception action and control NCEBP 9 - Mental health, Polymorphism, IGMD 3: Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory, Preschool, QH426, AUTISM SPECTRUM DISORDER, Human Genome, Psychology and Cognitive Sciences, Genetics and Genomics, Attention Deficit Hyperactivity Disorder (ADHD), R1, United Kingdom, United States, NICOTINIC RECEPTOR, Brain Disorders, Attention Deficit Disorder with Hyperactivity, Genomic, RC0321, DEFICIT/HYPERACTIVITY DISORDER, Neuroscience, Genome-Wide Association Study
alpha7 Nicotinic Acetylcholine Receptor, 150, Gene Dosage, Inheritance Patterns, Social Sciences, Psychiatry and Psychology, ASSOCIATION SCAN, DCN PAC - Perception action and control, *Attention Deficit Disorder with Hyperactivity, Receptors, Nicotinic, Nicotinic, NCMLS 6: Genetics and epigenetic pathways of disease, Medical and Health Sciences, MOLECULAR-GENETICS, Segmental Duplications, Genomic, SCHIZOPHRENIA, Receptors, 2.1 Biological and endogenous factors, Aetiology, Child, CHROMOSOMAL DELETIONS, In Situ Hybridization, In Situ Hybridization, Fluorescence, Pediatric, Psychiatry, Great Britain, Single Nucleotide, New Research, Serious Mental Illness, Segmental Duplications, Causality, Mental Health, Child, Preschool, Genes & Society, Female, DCN PAC - Perception action and control IGMD 3: Genomic disorders and inherited multi-system disorders, CANDIDATE GENE, 570, *Gene Dosage, Canada, Adolescent, DCN MP - Plasticity and memory, NCEBP 9: Mental health, 610, MICRODUPLICATIONS, Polymorphism, Single Nucleotide, Fluorescence, Clinical Research, 2738 Psychiatry and Mental health, 616, Genetics, ADHD, Humans, Genetic Predisposition to Disease, DCN PAC - Perception action and control NCEBP 9 - Mental health, Polymorphism, IGMD 3: Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory, Preschool, QH426, AUTISM SPECTRUM DISORDER, Human Genome, Psychology and Cognitive Sciences, Genetics and Genomics, Attention Deficit Hyperactivity Disorder (ADHD), R1, United Kingdom, United States, NICOTINIC RECEPTOR, Brain Disorders, Attention Deficit Disorder with Hyperactivity, Genomic, RC0321, DEFICIT/HYPERACTIVITY DISORDER, Neuroscience, Genome-Wide Association Study
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).253 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 0.1%
Citations provided by BIP!Popularity provided by BIP!