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RESEARCH PRODUCT

Candidate genetic pathways for attention-deficit/hyperactivity disorder (ADHD) show association to hyperactive/impulsive symptoms in children with ADHD

Richard P. EbsteinPhilip AshersonNanda RommelseMichael GillJoseph A. SergeantEdmund J.s. Sonuga-barkeAlejandro Arias-vasquezJaap OosterlaanCatharina A. HartmanHans-christoph SteinhausenBarbara FrankeIrwin D. WaldmanHerbert RoeyersAribert RothenbergerStephen V. FaraoneRobert D. OadesAna MirandaJan K. BuitelaarTobias BanaschewskiJanita Bralten

subject

Malegenetic pathwaysMedizinSocial SciencesGenome-wide association studyDCN PAC - Perception action and controlSeverity of Illness Index/dk/atira/pure/sustainabledevelopmentgoals/clean_water_and_sanitationneuritic outgrowth2738 Psychiatry and Mental HealthDOPAMINE0302 clinical medicineDevelopmental and Educational PsychologyIsraelChildQUANTITATIVE TRAITS10058 Department of Child and Adolescent PsychiatryGenomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3]EuropePsychiatry and Mental healthattention-deficit/hyperactivity disorder symptomsPhenotypeChild PreschoolFemalemedicine.symptomPsychologySDG 6 - Clean Water and Sanitationmedicine.drugClinical psychologymedicine.medical_specialtyDIAGNOSTIC-APPROACHAdolescentGenotypeLARGE MULTICENTER ADHDIDENTIFIES ASSOCIATIONDEFICIT HYPERACTIVITY DISORDERDCN MP - Plasticity and memoryneurotransmitter systems610 Medicine & healthQuantitative trait locusHyperkinesisImpulsivityMental health [NCEBP 9]Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3]03 medical and health sciencesDopamineRating scalemedicineCriterion validityddc:61Attention deficit hyperactivity disorderHumansddc:610Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie Psychosomatik und Psychotherapie des Kindes- und JugendaltersDCN PAC - Perception action and control NCEBP 9 - Mental healthGENOME-WIDE ASSOCIATIONNITRIC-OXIDE SYNTHASEPsychiatryGenetic Association StudiesMETAANALYSISPsychiatric Status Rating Scales3204 Developmental and Educational Psychologymedicine.disease030227 psychiatryAttention Deficit Disorder with HyperactivityImpulsive BehaviorEtiologyCRITERION VALIDITY030217 neurology & neurosurgery

description

Item does not contain fulltext OBJECTIVE: Because multiple genes with small effect sizes are assumed to play a role in attention-deficit/hyperactivity disorder (ADHD) etiology, considering multiple variants within the same analysis likely increases the total explained phenotypic variance, thereby boosting the power of genetic studies. This study investigated whether pathway-based analysis could bring scientists closer to unraveling the biology of ADHD. METHOD: The pathway was described as a predefined gene selection based on a well-established database or literature data. Common genetic variants in pathways involved in dopamine/norepinephrine and serotonin neurotransmission and genes involved in neuritic outgrowth were investigated in cases from the International Multicentre ADHD Genetics (IMAGE) study. Multivariable analysis was performed to combine the effects of single genetic variants within the pathway genes. Phenotypes were DSM-IV symptom counts for inattention and hyperactivity/impulsivity (n = 871) and symptom severity measured with the Conners Parent (n = 930) and Teacher (n = 916) Rating Scales. RESULTS: Summing genetic effects of common genetic variants within the pathways showed a significant association with hyperactive/impulsive symptoms (pempirical = .007) but not with inattentive symptoms (pempirical = .73). Analysis of parent-rated Conners hyperactive/impulsive symptom scores validated this result (pempirical = .0018). Teacher-rated Conners scores were not associated. Post hoc analyses showed a significant contribution of all pathways to the hyperactive/impulsive symptom domain (dopamine/norepinephrine, pempirical = .0004; serotonin, pempirical = .0149; neuritic outgrowth, pempirical = .0452). CONCLUSION: The present analysis shows an association between common variants in 3 genetic pathways and the hyperactive/impulsive component of ADHD. This study demonstrates that pathway-based association analyses, using quantitative measurements of ADHD symptom domains, can increase the power of genetic analyses to identify biological risk factors involved in this disorder.

yearjournalcountryeditionlanguage
2013-11-01
10.1016/j.jaac.2013.08.020https://hdl.handle.net/2066/125516