Parent-of-origin effect and risk for attention-deficit/hyperactivity disorder: balancing the evidence against bias and chance findings.
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ABSTRACT:
SUBMITTER: Joober R
PROVIDER: S-EPMC1592570 | biostudies-literature | 2006 Oct
REPOSITORIES: biostudies-literature
Publications
Parent-of-origin effect and risk for attention-deficit/hyperactivity disorder: balancing the evidence against bias and chance findings.
Joober Ridha R Sengupta Sarojini S
American journal of human genetics 20061001 4
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Project description:BackgroundPrevious studies have suggested that there may be a parent-of-origin effect for attention-deficit/hyperactivity disorder(ADHD) candidate genes. The objective of the present study was to investigate parent-of-origin effects using a genome-wide association analysis of the International Multicentre ADHD Genetics (IMAGE) study sample.MethodsFamily-based association analysis for ADHD using 846 ADHD probands and their parents was performed using the PLINK program, and parent-of-origin effects were studied using a Z score for the difference in paternal versus maternal odds ratios.ResultsWe identified 44 single nucleotide polymorphisms (SNPs) showing parent-of-origin effects at a significance level of p < 0.001. The most significant SNP, rs7614907, is at position 3q13.33 in the CDGAP gene (p = 0.000064 for parent-of-origin effect). Furthermore, 2 genes (FAS and PDLIM1) showed moderate parent-of-origin effects (p = 0.00086 for rs9658691 and p = 0.00077 for rs11188249) and strong maternal transmission (p = 0.000059 for rs9658691 and p = 0.0000068 for rs11188249). In addition, ZNF775 showed a moderate parent-of-origin effect (p = 0.00036 for rs7790549) and strong paternal transmission (p = 0.000041 for rs7790549).LimitationsWe only had 1 sample available for analysis.ConclusionThese results suggest several genes or regions with moderate parent-of-origin effects, and these findings will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in ADHD.
| S-EPMC3244498 | biostudies-literature
Project description:BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder sharing genetic risk factors with other common psychiatric disorders. However, intergenerational recurrence patterns of ADHD from parents to sons and daughters are not known. We aimed to examine the risk of ADHD in offspring of parents with ADHD and parents with other psychiatric disorders by parental and offspring sex, using parents without the specific disorders as comparison.MethodsIn a generation study linking data from several population-based registries, all Norwegians born 1967-2011 (n = 2,486,088; Medical Birth Registry of Norway) and their parents were followed to 2015. To estimate intergenerational recurrence risk, we calculated prevalence differences (PD) and the relative risk (RR) of ADHD in offspring by parental ADHD, bipolar disorder (BD), schizophrenia spectrum disorder (SCZ), major depression (MDD), all by parental and offspring sex.ResultsThe absolute prevalence of ADHD in offspring of parents with ADHD was very high, especially in sons of two affected parents (41.5% and 25.1% in sons and daughters, respectively), and far higher than in offspring of parents with BD, SCZ or MDD. Intergenerational recurrence risks were higher for maternal than paternal ADHD (RRmaternal 8.4, 95% confidence interval (CI) 8.2-8.6 vs. RRpaternal 6.2, 6.0-6.4) and this was also true on the absolute scale (PDmaternal 21.1% (20.5-21.7) vs. PDpaternal 14.8% (14.3-15.4)). RRs were higher in daughters, while PDs higher in sons. Parental SCZ, BD and MDD were associated with an approximately doubled risk of offspring ADHD compared to parents without the respective disorders, and estimates did not differ significantly between daughters and sons.ConclusionsThe intergenerational recurrence risks of ADHD were high and higher from mothers with ADHD than fathers with ADHD. Other parental psychiatric disorders also conferred increased risk of offspring ADHD, but far lower, indicating a sex- and diagnosis-specific intergenerational recurrence risk in parents with ADHD.
| S-EPMC8451909 | biostudies-literature
Project description:Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a long-term impact on functioning, productivity and quality of life of patients. This impact is largely due to the symptoms of inattentiveness. However, despite its impairing role in the lives of ADHD patients, inattentiveness has been studied relatively less frequently than have symptoms of impulsivity/hyperactivity and problems with executive function. This review therefore seeks to integrate the neuropsychological theories and current findings in the research fields of neuropsychology, neurophysiology, and neuroimaging, in an attempt to gain a more complete understanding of the role that inattentiveness plays in ADHD, as well as to suggest directions for future studies. The need for a more comprehensive understanding of inattentiveness and ADHD, which integrates findings from each of the three disciplines mentioned above, is emphasized.
| S-EPMC4440572 | biostudies-other
Project description:Attention-deficit hyperactivity disorder (ADHD), like other psychiatric disorders, represents an evolving construct that has been refined and developed over the past several decades in response to research into its clinical nature and structure. The clinical presentation and course of the disorder have been extensively characterised. Efficacious medication-based treatments are available and widely used, often alongside complementary psychosocial approaches. However, their effectiveness has been questioned because they might not address the broader clinical needs of many individuals with ADHD, especially over the longer term. Non-pharmacological approaches to treatment have proven less effective than previously thought, whereas scientific and clinical studies are starting to fundamentally challenge current conceptions of the causes of ADHD in ways that might have the potential to alter clinical approaches in the future. In view of this, we first provide an account of the diagnosis, epidemiology, and treatment of ADHD from the perspective of both the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and the eleventh edition of the International Classification of Diseases. Second, we review the progress in our understanding of the causes and pathophysiology of ADHD on the basis of science over the past decade or so. Finally, using these discoveries, we explore some of the key challenges to both the current models and the treatment of ADHD, and the ways in which these findings can promote new perspectives.
| S-EPMC7880081 | biostudies-literature
Project description:BackgroundAssociations between attention-deficit/hyperactivity disorder (ADHD) and brain morphology have been reported, although with several inconsistencies. These may partly stem from confounding bias, which could distort associations and limit generalizability. We examined how associations between brain morphology and ADHD symptoms change with adjustments for potential confounders typically overlooked in the literature (aim 1), and for the intelligence quotient (IQ) and head motion, which are generally corrected for but play ambiguous roles (aim 2).MethodsParticipants were 10-year-old children from the Adolescent Brain Cognitive Development (N = 7722) and Generation R (N = 2531) Studies. Cortical area, volume, and thickness were measured with MRI and ADHD symptoms with the Child Behavior Checklist. Surface-based cross-sectional analyses were run.ResultsADHD symptoms related to widespread cortical regions when solely adjusting for demographic factors. Additional adjustments for socioeconomic and maternal behavioral confounders (aim 1) generally attenuated associations, as cluster sizes halved and effect sizes substantially reduced. Cluster sizes further changed when including IQ and head motion (aim 2), however, we argue that adjustments might have introduced bias.ConclusionsCareful confounder selection and control can help identify more robust and specific regions of associations for ADHD symptoms, across two cohorts. We provided guidance to minimizing confounding bias in psychiatric neuroimaging.FundingAuthors are supported by an NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200 to HT) for HT, LDA, SL, and the Sophia Foundation S18-20, and Erasmus University and Erasmus MC Fellowship for RLM.
| S-EPMC9708072 | biostudies-literature
Project description:Genetic Investigations of Attention-Deficit/Hyperactivity Disorder
| PRJNA1114309 | ENA
Project description:Genetic Investigations of Attention-Deficit/Hyperactivity Disorder
| PRJNA1114310 | ENA
Project description: Not available
| S-EPMC3796623 | biostudies-literature
Project description:The occurrence of attention deficit-hyperactivity disorder (ADHD) symptoms in patients with cystic fibrosis (CF) is substantially higher than in the general population, and the cystic fibrosis transmembrane conductance regulator (CFTR) is the pathogenic gene of cystic fibrosis, suggesting the potentially critical role of CFTR in ADHD. Here, we identified three heterozygous missense mutations (p.E217G, p.F316L and p.T1220I) in CFTR, segregating with ADHD in two consanguineous families with 6 affected individuals. Using the zebrafish model, we found that the cftr knockout line displays hyperactive, impulsive-like, and attention deficit-like behaviors, reminiscent of human ADHD patients. Single-cell RNA-seq of 7 dpf larvae identified clusters of neuron cells that were sensitive to cftr, especially, the number of dopaminergic neuron cells decreased in the cftr mutant fish. Bulk RNA-seq and proteomic analysis at the early gastrulation period showed that the expression of nerve system genes was abnormal. Notably, we tried to use CFTR activitors Lumacaftor (VX-809) and Ivacaftor (VX-770) to treat the ADHD zebrafish model (established by per1b mutant), and found enhanced CFTR activity could rescue the ADHD-like behaviors. In brief, we uncover the role of CFTR in ADHD pathogenesis and explore novel diagnoses and therapy for ADHD by targeting CFTR.
2024-12-16 | GSE284214 | GEO
Project description:High rates of comorbidity and overlapping diagnostic criteria between pediatric bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) contribute to diagnostic and treatment confusion. To advance what is known about both disorders, we compared effect of emotional stimuli on response control in children with primary BD, primary ADHD and typically developing controls (TDC). Participants included 7-17 year olds with either "narrow-phenotype" pediatric BD (n = 25), ADHD (n = 25) or TDC (n = 25). Groups were matched on participant age and FSIQ. The effect of emotional stimuli on response control was assessed using the Cambridge Neuropsychological Test Automated Battery Affective Go/No-Go task (CANTAB AGN). We found a group by target valence interaction on commission errors [F(2,71) = 5.34, p < 0.01, ƞ p (2) = 0.13] whereby ADHD, but not TDC participants, made more errors on negative than positive words [t(24) = -2.58, p < 0.05, r = 0.47]. In contrast, there was a nonsignificant trend for BD participants to make fewer errors on negative versus positive words compared to ADHD and TDC participants. Between-subjects effects showed that ADHD participants made more errors than TDC, but not BD participants. Our main finding advances what is known about the effect of emotional stimuli on response control in children with ADHD. Our results suggesting a positive affective processing bias in children with ADHD compliment emerging literature show that difficulties with emotional processing and regulation may be core features of ADHD. Further, given the observed pattern of results in children with ADHD compared to BD children, our behavioral results suggest the importance of examining differences in the brain-behavior mechanisms involved in affective processing in children with ADHD compared to BD children.
| S-EPMC6518415 | biostudies-literature