Genome-wide association study of conduct disorder symptomatology

D. M. Dick, F. Aliev, R. F. Krueger, A. Edwards, A. Agrawal, M. Lynskey, P. Lin, M. Schuckit, V. Hesselbrock, J. Nurnberger, L. Almasy, B. Porjesz, H. J. Edenberg, K. Bucholz, J. Kramer, S. Kuperman, L. Bierut

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

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 (N872 with CD and N3091 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.

Original languageEnglish (US)
Pages (from-to)800-808
Number of pages9
JournalMolecular psychiatry
Volume16
Issue number8
DOIs
StatePublished - Aug 2011

Bibliographical note

Funding Information:
Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422). SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392), and the Family Study of Cocaine Dependence (FSCD; R01 DA013423). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract ‘High throughput genotyping for studying the genetic contributions to human disease’ (HHSN268200782096C). This project also was supported by a 2007 NARSAD Young Investigator Award to Danielle M. Dick.

Keywords

  • GWAS
  • association analysis
  • conduct disorder
  • genetics

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