Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Shared genetic background between children and adults with attention deficit/hyperactivity disorder.

ABSTRACT: Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and jointly, and by comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children, and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.

SUBMITTER: Rovira P

PROVIDER: S-EPMC7419307 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Shared genetic architecture between attention-deficit/hyperactivity disorder and lifespan.

Project description:There is evidence linking ADHD to a reduced life expectancy. The mortality rate in individuals with ADHD is twice that of the general population and it is associated with several factors, such as unhealthy lifestyle behaviors, social adversity, and mental health problems that may in turn increase mortality rates. Since ADHD and lifespan are heritable, we used data from genome-wide association studies (GWAS) of ADHD and parental lifespan, as proxy of individual lifespan, to estimate their genetic correlation, identify genetic loci jointly associated with both phenotypes and assess causality. We confirmed a negative genetic correlation between ADHD and parental lifespan (rg = -0.36, P = 1.41e-16). Nineteen independent loci were jointly associated with both ADHD and parental lifespan, with most of the alleles that increased the risk for ADHD being associated with shorter lifespan. Fifteen loci were novel for ADHD and two were already present in the original GWAS on parental lifespan. Mendelian randomization analyses pointed towards a negative causal effect of ADHD liability on lifespan (P = 1.54e-06; Beta = -0.07), although these results were not confirmed by all sensitivity analyses performed, and further evidence is required. The present study provides the first evidence of a common genetic background between ADHD and lifespan, which may play a role in the reported effect of ADHD on premature mortality risk. These results are consistent with previous epidemiological data describing reduced lifespan in mental disorders and support that ADHD is an important health condition that could negatively affect future life outcomes.

| S-EPMC10209393 | biostudies-literature

Polygenic risk score analysis revealed shared genetic background in attention deficit hyperactivity disorder and narcolepsy.

Project description:Attention deficit hyperactive disorder (ADHD) is a highly heritable neurodevelopmental disorder, and excessive daytime sleepiness is frequently observed in ADHD patients. Excessive daytime sleepiness is also a core symptom of narcolepsy and essential hypersomnia (EHS), which are also heritable conditions. Psychostimulants are effective for the symptomatic control of ADHD (primary recommended intervention) and the two sleep disorders (frequent off-label use). However, the common biological mechanism for these disorders has not been well understood. Using a previously collected genome-wide association study of narcolepsy and EHS, we calculated polygenic risk scores (PRS) for each individual. We investigated a possible genetic association between ADHD and narcolepsy traits in the Hamamatsu Birth Cohort for mothers and children (HBC study) (n = 876). Gene-set enrichment analyses were used to identify common pathways underlying these disorders. Narcolepsy PRS were significantly associated with ADHD traits both in the hyperactivity domain (e.g., P-value threshold < 0.05, β [SE], 5.815 [1.774]; P = 0.002) and inattention domain (e.g., P-value threshold < 0.05, β [SE], 5.734 [1.761]; P = 0.004). However, EHS PRS was not significantly associated with either domain of ADHD traits. Gene-set enrichment analyses revealed that pathways related to dopaminergic signaling, immune systems, iron metabolism, and glial cell function involved in both ADHD and narcolepsy. Findings indicate that ADHD and narcolepsy are genetically related, and there are possible common underlying biological mechanisms for this relationship. Future studies replicating these findings would be warranted to elucidate the genetic vulnerability for daytime sleepiness in individuals with ADHD.

| S-EPMC7429956 | biostudies-literature

Common and Unique Genetic Background between Attention-Deficit/Hyperactivity Disorder and Excessive Body Weight.

Project description:Comorbidity studies show that children with ADHD have a higher risk of being overweight and obese than healthy children. This study aimed to assess the genetic alternations that differ between and are shared by ADHD and excessive body weight (EBW). The sample consisted of 743 Polish children aged between 6 and 17 years. We analyzed a unique set of genes and polymorphisms selected for ADHD and/or obesity based on gene prioritization tools. Polymorphisms in the KCNIP1, SLC1A3, MTHFR, ADRA2A, and SLC6A2 genes proved to be associated with the risk of ADHD in the studied population. The COMT gene polymorphism was one that specifically increased the risk of EBW in the ADHD group. Using the whole-exome sequencing technique, we have shown that the ADHD group contains rare and protein-truncating variants in the FBXL17, DBH, MTHFR, PCDH7, RSPH3, SPTBN1, and TNRC6C genes. In turn, variants in the ADRA2A, DYNC1H1, MAP1A, SEMA6D, and ZNF536 genes were specific for ADHD with EBW. In this way, we confirmed, at the molecular level, the existence of genes specifically predisposing to EBW in ADHD patients, which are associated with the biological pathways involved in the regulation of the reward system, intestinal microbiome, and muscle metabolism.

| S-EPMC8464917 | biostudies-literature

Shared and distinct resting functional connectivity in children and adults with attention-deficit/hyperactivity disorder.

Project description:Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood, with a shift of symptoms including less hyperactivity/impulsivity and more co-morbidity of affective disorders in ADHDadult. Many studies have questioned the stability in diagnosing of ADHD from childhood to adulthood, and the shared and distinct aberrant functional connectivities (FCs) between ADHDchild and ADHDadult remain unidentified. We aim to explore shared and distinct FC patterns in ADHDchild and ADHDadult, and further investigated the cross-cohort predictability using the identified FCs. After investigating the ADHD-discriminative FCs from healthy controls (HCs) in both child (34 ADHDchild, 28 HCs) and adult (112 ADHDadult,77 HCs) cohorts, we identified both shared and distinct aberrant FC patterns between cohorts and their association with clinical symptoms. Moreover, the cross-cohort predictability using the identified FCs were tested. The ADHD-HC classification accuracies were 84.4% and 81.0% for children and male adults, respectively. The ADHD-discriminative FCs shared in children and adults lie in the intra-network within default mode network (DMN) and the inter-network between DMN and ventral attention network, positively correlated with total scores of ADHD symptoms. Particularly, inter-network FC between somatomotor network and dorsal attention network was uniquely impaired in ADHDchild, positively correlated with hyperactivity index; whereas the aberrant inter-network FC between DMN and limbic network exhibited more adult-specific ADHD dysfunction. And their cross-cohort predictions were 70.4% and 75.6% between each other. This work provided imaging evidence for symptomatic changes and pathophysiological continuity in ADHD from childhood to adulthood, suggesting that FCs may serve as potential biomarkers for ADHD diagnosis.

| S-EPMC7026417 | biostudies-literature

Identification of Genetic Loci Shared Between Attention-Deficit/Hyperactivity Disorder, Intelligence, and Educational Attainment.

Project description:BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is consistently associated with lower levels of educational attainment. A recent large genome-wide association study identified common gene variants associated with ADHD, but most of the genetic architecture remains unknown.MethodsWe analyzed independent genome-wide association study summary statistics for ADHD (19,099 cases and 34,194 controls), educational attainment (N = 842,499), and general intelligence (N = 269,867) using a conditional/conjunctional false discovery rate (FDR) statistical framework that increases power of discovery by conditioning the FDR on overlapping associations. The genetic variants identified were characterized in terms of function, expression, and biological processes.ResultsWe identified 58 linkage disequilibrium-independent ADHD-associated loci (conditional FDR < 0.01), of which 30 were shared between ADHD and educational attainment or general intelligence (conjunctional FDR < 0.01) and 46 were novel risk loci for ADHD.ConclusionsThese results expand on previous genetic and epidemiological studies and support the hypothesis of a shared genetic basis between these phenotypes. Although the clinical utility of the identified loci remains to be determined, they can be used as resources to guide future studies aiming to disentangle the complex etiologies of ADHD, educational attainment, and general intelligence.

| S-EPMC7255939 | biostudies-literature

Genetic Investigations of Attention-Deficit/Hyperactivity Disorder

Project description:Genetic Investigations of Attention-Deficit/Hyperactivity Disorder

| PRJNA1114309 | ENA

Genetic Investigations of Attention-Deficit/Hyperactivity Disorder

Project description:Genetic Investigations of Attention-Deficit/Hyperactivity Disorder

| PRJNA1114310 | ENA

Association between atopic dermatitis and attention deficit hyperactivity disorder in U.S. children and adults.

Project description:BackgroundAtopic dermatitis (AD) is associated with chronic itch, allergic disease and sleep disturbance, all of which might increase the risk of attention deficit (hyperactivity) disorder (ADD/ADHD). Previous analyses have found a consistent association between AD and ADD/ADHD, although the underlying factors contributing to such an association remain underexplored. Additionally, the relationship has been underexplored in adults.ObjectivesTo determine if childhood and adult AD and AD severity are associated with ADD/ADHD and to delineate the factors contributing to such an association.MethodsWe analysed data on 354 416 children aged 2-17 years and 34 613 adults age 18+ years from 19 U.S. population-based surveys, including the National Health Interview Survey 1997-2013 and the National Survey of Children's Health 2003/4 and 2007/8.ResultsIn multivariate models adjusting for age, sex, sociodemographics, allergic disease and healthcare utilization, AD was associated with ADD/ADHD in both children [adjusted odds ratio (95% confidence interval), 1·14 (1·03-1·26)] and adults [1·61 (1·25-2·06)]. Children with both severe AD and only 0-3 nights of adequate sleep per week had much higher odds of ADD/ADHD [16·83 (7·02-40·33)] than those with 0-3 nights of adequate sleep per week [1·83 (1·47-2·26)] or mild-moderate AD alone [1·56 (1·22-1·99)]. AD was most strongly associated with severe ADHD. AD unaccompanied by other allergic disease was also associated with increased risk of ADD/ADHD in children. Among children with AD, history of anaemia, headaches and obesity were associated with even higher odds of ADD/ADHD. Asthma, insomnia and headaches increased the odds of ADHD in adults with AD, although underweight body mass index was protective.ConclusionsAtopic dermatitis is associated with increased odds of ADD/ADHD in adults and children. Several factors increase the risk of ADHD in adults and children with AD.

| S-EPMC5216180 | biostudies-literature

Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder.

Project description:Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20-50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting criteria for ADHD. This review will provide an overview on all available studies [family based, twin, candidate gene, linkage, and genome wide association (GWA) studies] shedding light on the role of shared genetic underpinnings of ADHD and ASD. It is concluded that family and twin studies do provide support for the hypothesis that ADHD and ASD originate from partly similar familial/genetic factors. Only a few candidate gene studies, linkage studies and GWA studies have specifically addressed this co-occurrence, pinpointing to some promising pleiotropic genes, loci and single nucleotide polymorphisms (SNPs), but the research field is in urgent need for better designed and powered studies to tackle this complex issue. We propose that future studies examining shared familial etiological factors for ADHD and ASD use a family-based design in which the same phenotypic (ADHD and ASD), candidate endophenotypic, and environmental measurements are obtained from all family members. Multivariate multi-level models are probably best suited for the statistical analysis.

| S-EPMC2839489 | biostudies-literature

Genetic and environmental influences on the relation between attention problems and attention deficit hyperactivity disorder.

Project description:The assessment of symptoms of ADHD in children is usually based on a clinical interview or a behavior checklist. The aim of the present study is to investigate the extent to which these instruments measure an underlying construct and to estimate the genetic and environmental influences on individual differences in ADHD.Maternal ratings were collected on 10,916 twins from 5,458 families. Child Behavior Checklist (CBCL) ratings were available for 10,018, 6,565, and 5,780 twins at the ages 7, 10, and 12, respectively. The Conners Rating Scale (4,887 twins) and the DSM interview (1,006 twins) were completed at age 12. The magnitude of genetic and environmental influences on the variance of the three measures of ADHD and the covariance among the three measures of ADHD was obtained.Phenotypic correlations range between .45 and .77. Variances and covariances of the measurements were explained mainly by genetic influences. The model that provided the best account of the data included an independent pathway for additive and dominant genetic effects. The genetic correlations among the measures collected at age 12 varied between .63 and 1.00.The genetic overlap between questionnaire ratings and the DSM-IV diagnosis of ADHD is high. Clinical and research implications of these findings are presented.

| S-EPMC2226020 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data