Genome-Wide Association Study of Behavioral Disinhibition in a Selected Adolescent Sample

Jaime Derringer; Robin P. Corley; Brett C. Haberstick; Susan E. Young; Brittany A. Demmitt; Daniel P. Howrigan; Robert M. Kirkpatrick; William G. Iacono; Matt McGue; Matthew C. Keller; Sandra Brown; Susan Tapert; Christian J. Hopfer; Michael C. Stallings; Thomas J. Crowley; Soo Hyun Rhee; Ken Krauter; John K. Hewitt; Matthew B. McQueen

doi:10.1007/s10519-015-9705-y

Genome-Wide Association Study of Behavioral Disinhibition in a Selected Adolescent Sample

Jaime Derringer, Robin P. Corley, Brett C. Haberstick, Susan E. Young, Brittany A. Demmitt, Daniel P. Howrigan, Robert M. Kirkpatrick, William G. Iacono, Matt McGue, Matthew C. Keller, Sandra Brown, Susan Tapert, Christian J. Hopfer, Michael C. Stallings, Thomas J. Crowley, Soo Hyun Rhee, Ken Krauter, John K. Hewitt, Matthew B. McQueen

Psychology (Twin Cities)

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Behavioral disinhibition (BD) is a quantitative measure designed to capture the heritable variation encompassing risky and impulsive behaviors. As a result, BD represents an ideal target for discovering genetic loci that predispose individuals to a wide range of antisocial behaviors and substance misuse that together represent a large cost to society as a whole. Published genome-wide association studies (GWAS) have examined specific phenotypes that fall under the umbrella of BD (e.g. alcohol dependence, conduct disorder); however no GWAS has specifically examined the overall BD construct. We conducted a GWAS of BD using a sample of 1,901 adolescents over-selected for characteristics that define high BD, such as substance and antisocial behavior problems, finding no individual locus that surpassed genome-wide significance. Although no single SNP was significantly associated with BD, restricted maximum likelihood analysis estimated that 49.3 % of the variance in BD within the Caucasian sub-sample was accounted for by the genotyped SNPs (p = 0.06). Gene-based tests identified seven genes associated with BD (p ≤ 2.0 × 10⁻⁶). Although the current study was unable to identify specific SNPs or pathways with replicable effects on BD, the substantial sample variance that could be explained by all genotyped SNPs suggests that larger studies could successfully identify common variants associated with BD.

Original language	English (US)
Pages (from-to)	375-381
Number of pages	7
Journal	Behavior genetics
Volume	45
Issue number	4
DOIs	https://doi.org/10.1007/s10519-015-9705-y
State	Published - Jul 9 2015

Bibliographical note

Funding Information:
The Center on Antisocial Drug Dependence (CADD) data reported here were funded by grants from the National Institute on Drug Abuse (P60 DA011015, R01 DA012845, R01 DA021913, R01 DA021905). The Minnesota Center for Twin and Family Research (MCTFR) was supported in part by USPHS Grants from the National Institute on Alcohol Abuse and Alcoholism (AA09367 and AA11886), the National Institute on Drug Abuse (DA05147, DA13240, and DA024417), and the National Institute of Mental Health (MH066140). 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). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000092.v1.p1 through dbGaP accession number phs000092.v1.p. Jaime Derringer was supported by the National Institute of Mental Health (T32 MH016880).

Publisher Copyright:
© 2015, Springer Science+Business Media New York.

Keywords

Behavioral disinhibition
GWAS
Heritability
Pathway analysis

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10.1007/s10519-015-9705-y

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Derringer, J., Corley, R. P., Haberstick, B. C., Young, S. E., Demmitt, B. A., Howrigan, D. P., Kirkpatrick, R. M., Iacono, W. G., McGue, M., Keller, M. C., Brown, S., Tapert, S., Hopfer, C. J., Stallings, M. C., Crowley, T. J., Rhee, S. H., Krauter, K., Hewitt, J. K., & McQueen, M. B. (2015). Genome-Wide Association Study of Behavioral Disinhibition in a Selected Adolescent Sample. Behavior genetics, 45(4), 375-381. https://doi.org/10.1007/s10519-015-9705-y

Derringer, J, Corley, RP, Haberstick, BC, Young, SE, Demmitt, BA, Howrigan, DP, Kirkpatrick, RM, Iacono, WG, McGue, M, Keller, MC, Brown, S, Tapert, S, Hopfer, CJ, Stallings, MC, Crowley, TJ, Rhee, SH, Krauter, K, Hewitt, JK & McQueen, MB 2015, 'Genome-Wide Association Study of Behavioral Disinhibition in a Selected Adolescent Sample', Behavior genetics, vol. 45, no. 4, pp. 375-381. https://doi.org/10.1007/s10519-015-9705-y

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abstract = "Behavioral disinhibition (BD) is a quantitative measure designed to capture the heritable variation encompassing risky and impulsive behaviors. As a result, BD represents an ideal target for discovering genetic loci that predispose individuals to a wide range of antisocial behaviors and substance misuse that together represent a large cost to society as a whole. Published genome-wide association studies (GWAS) have examined specific phenotypes that fall under the umbrella of BD (e.g. alcohol dependence, conduct disorder); however no GWAS has specifically examined the overall BD construct. We conducted a GWAS of BD using a sample of 1,901 adolescents over-selected for characteristics that define high BD, such as substance and antisocial behavior problems, finding no individual locus that surpassed genome-wide significance. Although no single SNP was significantly associated with BD, restricted maximum likelihood analysis estimated that 49.3 % of the variance in BD within the Caucasian sub-sample was accounted for by the genotyped SNPs (p = 0.06). Gene-based tests identified seven genes associated with BD (p ≤ 2.0 × 10−6). Although the current study was unable to identify specific SNPs or pathways with replicable effects on BD, the substantial sample variance that could be explained by all genotyped SNPs suggests that larger studies could successfully identify common variants associated with BD.",

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note = "Funding Information: The Center on Antisocial Drug Dependence (CADD) data reported here were funded by grants from the National Institute on Drug Abuse (P60 DA011015, R01 DA012845, R01 DA021913, R01 DA021905). The Minnesota Center for Twin and Family Research (MCTFR) was supported in part by USPHS Grants from the National Institute on Alcohol Abuse and Alcoholism (AA09367 and AA11886), the National Institute on Drug Abuse (DA05147, DA13240, and DA024417), and the National Institute of Mental Health (MH066140). 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). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000092.v1.p1 through dbGaP accession number phs000092.v1.p. Jaime Derringer was supported by the National Institute of Mental Health (T32 MH016880). Publisher Copyright: {\textcopyright} 2015, Springer Science+Business Media New York.",

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Genome-Wide Association Study of Behavioral Disinhibition in a Selected Adolescent Sample

Abstract

Bibliographical note

Keywords

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