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RESEARCH PRODUCT
Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations
Wai ChenNan M. LairdJoseph A. SergeantTobias BanaschewskiHans-christoph SteinhausenHerbert RoeyersRichard P. EbsteinPhilip AshersonJulian MallerAribert RothenbergerAna MirandaEdmund J.s. Sonuga-barkeMichael GillMark J. DalyMark J. DalyChristoph LangeChristoph LangeEric TaylorRobert D. OadesJessica Lasky-suKaixin ZhouFernando MulasBarbara FrankeBenjamin M. NealeRichard AnneyStephen V. FaraoneAlejandro Arias VasquezJan K. Buitelaarsubject
MaleCandidate geneGenetics and epigenetic pathways of disease [NCMLS 6]2804 Cellular and Molecular NeuroscienceMedizinGenome-wide association studyNeuroinformatics [DCN 3]Genome2738 Psychiatry and Mental Health0302 clinical medicinePerception and Action [DCN 1]Cluster AnalysisGenetics(clinical)Genetics (clinical)Genetics0303 health sciences10058 Department of Child and Adolescent PsychiatryCadherinsPedigreePsychiatry and Mental healthFemaleFunctional Neurogenomics [DCN 2]CDH13AlgorithmsGenetic Markers2716 Genetics (clinical)GenotypeQuantitative Trait Loci610 Medicine & healthSingle-nucleotide polymorphismBiologyQuantitative trait locusPolymorphism Single NucleotideMental health [NCEBP 9]Genetic determinismGenomic disorders and inherited multi-system disorders [IGMD 3]03 medical and health sciencesCellular and Molecular NeuroscienceCognitive neurosciences [UMCN 3.2]medicineADHDAttention deficit hyperactivity disorderHumansGenetic Predisposition to Diseaseddc:610Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie Psychosomatik und Psychotherapie des Kindes- und JugendaltersGene030304 developmental biologyProbabilityModels GeneticGenome Humancandidate genefamily-based associationmedicine.diseaseIntronsHaplotypesGenetic defects of metabolism [UMCN 5.1]Attention Deficit Disorder with Hyperactivitygenome-wide association030217 neurology & neurosurgeryGenome-Wide Association Studydescription
Contains fulltext : 70192.pdf (Publisher’s version ) (Closed access) Attention deficit hyperactivity disorder (ADHD) is a complex condition with environmental and genetic etiologies. Up to this point, research has identified genetic associations with candidate genes from known biological pathways. In order to identify novel ADHD susceptibility genes, 600,000 SNPs were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. We generated six quantitative phenotypes from 18 ADHD symptoms to be used in genome-wide association analyses. With the PBAT screening algorithm, we identified 2 SNPs, rs6565113 and rs552655 that met the criteria for significance within a specified phenotype. These SNPs are located in intronic regions of genes CDH13 and GFOD1, respectively. CDH13 has been implicated previously in substance use disorders. We also evaluated the association of SNPs from a list of 37 ADHD candidate genes that was specified a priori. These findings, along with association P-values with a magnitude less than 10(-5), are discussed in this manuscript. Seventeen of these candidate genes had association P-values lower then 0.01: SLC6A1, SLC9A9, HES1, ADRB2, HTR1E, DDC, ADRA1A, DBH, DRD2, BDNF, TPH2, HTR2A, SLC6A2, PER1, CHRNA4, SNAP25, and COMT. Among the candidate genes, SLC9A9 had the strongest overall associations with 58 association test P-values lower than 0.01 and multiple association P-values at a magnitude of 10(-5) in this gene. In sum, these findings identify novel genetic associations at viable ADHD candidate genes and provide confirmatory evidence for associations at previous candidate genes. Replication of these results is necessary in order to confirm the proposed genetic variants for ADHD.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2008-01-01 | American Journal of Medical Genetics Part B: Neuropsychiatric Genetics |