title: Genome-wide association study of conduct disorder symptomatology.
abstract: Conduct disorder (CD) is one of the most prevalent childhood psychiatric conditions, and is associated with a number of serious concomitant and future problems. CD symptomatology is known to have a considerable genetic component, with heritability estimates in the range of 50%. Despite this, there is a relative paucity of studies aimed at identifying genes involved in the susceptibility to CD. In this study, we report results from a genome-wide association study of CD symptoms. CD symptoms were retrospectively reported by a psychiatric interview among a sample of cases and controls, in which cases met the criteria for alcohol dependence. Our primary phenotype was the natural log transformation of the number of CD symptoms that were endorsed, with data available for 3963 individuals who were genotyped on the Illumina Human 1M beadchip array. Secondary analyses are presented for case versus control status, in which caseness was established as endorsing three or more CD symptoms (N = 872 with CD and N = 3091 without CD). We find four markers that meet the criteria for genome-wide significance (P<5 × 10(-8)) with the CD symptom count, two of which are located in the gene C1QTNF7 (C1q and tumor necrosis factor-related protein 7). There were six additional SNPs in the gene that yielded converging evidence of association. These data provide the first evidence of a specific gene that is associated with CD symptomatology. None of the top signals resided in traditional candidate genes, underscoring the importance of a genome-wide approach for identifying novel variants involved in this serious childhood disorder.
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA. ddick@vcu.edu
authors.forename: D M
authors.initials: DM
authors.lastname: Dick
authors.forename: F
authors.initials: F
authors.lastname: Aliev
authors.forename: R F
authors.initials: RF
authors.lastname: Krueger
authors.forename: A
authors.initials: A
authors.lastname: Edwards
authors.forename: A
authors.initials: A
authors.lastname: Agrawal
authors.forename: M
authors.initials: M
authors.lastname: Lynskey
authors.forename: P
authors.initials: P
authors.lastname: Lin
authors.forename: M
authors.initials: M
authors.lastname: Schuckit
authors.forename: V
authors.initials: V
authors.lastname: Hesselbrock
authors.forename: J
authors.initials: J
authors.lastname: Nurnberger
authors.forename: L
authors.initials: L
authors.lastname: Almasy
authors.forename: B
authors.initials: B
authors.lastname: Porjesz
authors.forename: H J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: K
authors.initials: K
authors.lastname: Bucholz
authors.forename: J
authors.initials: J
authors.lastname: Kramer
authors.forename: S
authors.initials: S
authors.lastname: Kuperman
authors.forename: L
authors.initials: L
authors.lastname: Bierut
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D019955:Conduct Disorder / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D017831:Diagnosis, Dual (Psychiatry) / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies