title: Genome-wide pathway analysis in attention-deficit/hyperactivity disorder.
abstract: This study aimed to (1) to identify candidate single-nucleotide polymorphisms (SNPs) and mechanisms of attention-deficit/hyperactivity disorder (ADHD) and (2) to generate SNP-to-gene-to-pathway hypotheses. An ADHD genome-wide association study (GWAS) dataset that included 428,074 SNPs in 924 trios (2,758 individuals) of European descent was used in this study. The Identify candidate Causal SNPs and Pathways (ICSNPathway) analysis was applied to the GWAS dataset. ICSNPathway analysis identified 11 candidate SNPs, 6 genes, and 6 pathways, which provided 6 hypothetical biological mechanisms. The strongest hypothetical biological mechanism was that rs2532502 alters the role of CD27 in the context of the pathways of positive regulation of nucleocytoplasmic transport [nominal p < 0.001; false discovery rate (FDR) = 0.028]. The second strongest mechanism was the rs1820204, rs1052571, rs1052576 → CASP9 → mitochondrial pathway (nominal p < 0.001; FDR = 0.032). The third mechanism was the rs1801516 → ATM → CD25 pathway (nominal p < 0.001; FDR = 0.034). By applying the ICSNPathway analysis to the ADHD GWAS data, 11 candidate SNPs, 6 genes that included CD27, CASP9, ATM, CD12orf65, OXER1, and ACRY, and 6 pathways were identified that may contribute to ADHD susceptibility.
authors: Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1 5 ga, Anam-dong, Seongbuk-gu, Seoul, 136-705, Korea, lyhcgh@korea.ac.kr.
authors: Young Ho
authors: YH
authors: Lee
authors: Gwan Gyu
authors: GG
authors: Song
mesh_terms: D001275:ATP Citrate (pro-S)-Lyase / Q000235:genetics / Q000502:physiology; D000293:Adolescent; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000502:physiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D053453:Caspase 9 / Q000235:genetics / Q000502:physiology; D015984:Causality; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology; D008957:Models, Genetic; D010454:Peptide Termination Factors / Q000235:genetics / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D018055:Receptors, Eicosanoid / Q000235:genetics / Q000502:physiology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000502:physiology
chemical_list: D001275:ATP Citrate (pro-S)-Lyase; D064007:Ataxia Telangiectasia Mutated Proteins; D053453:Caspase 9; D024101:Mitochondrial Proteins; D010454:Peptide Termination Factors; D018055:Receptors, Eicosanoid; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C551030:MTRFR protein, human; C504018:OXER1 protein, human; C576324:ATM protein, human; C506433:CASP9 protein, human