title: Genome-Wide Association Study of Behavioral Disinhibition in a Selected Adolescent Sample.
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.
authors: Department of Psychology, University of Illinois Urbana-Champaign, Champaign, IL, 61820, USA, jderr@illinois.edu.
authors: Jaime
authors: J
authors: Derringer
authors: Robin P
authors: RP
authors: Corley
authors: Brett C
authors: BC
authors: Haberstick
authors: Susan E
authors: SE
authors: Young
authors: Brittany A
authors: BA
authors: Demmitt
authors: Daniel P
authors: DP
authors: Howrigan
authors: Robert M
authors: RM
authors: Kirkpatrick
authors: William G
authors: WG
authors: Iacono
authors: Matt
authors: M
authors: McGue
authors: Matthew C
authors: MC
authors: Keller
authors: Sandra
authors: S
authors: Brown
authors: Susan
authors: S
authors: Tapert
authors: Christian J
authors: CJ
authors: Hopfer
authors: Michael C
authors: MC
authors: Stallings
authors: Thomas J
authors: TJ
authors: Crowley
authors: Soo Hyun
authors: SH
authors: Rhee
authors: Ken
authors: K
authors: Krauter
authors: John K
authors: JK
authors: Hewitt
authors: Matthew B
authors: MB
authors: McQueen
mesh_terms: D000293:Adolescent; D000437:Alcoholism / Q000235:genetics; D000483:Alleles; D000987:Antisocial Personality Disorder / Q000235:genetics*; D019955:Conduct Disorder / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007175:Impulsive Behavior; D016013:Likelihood Functions; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012309:Risk-Taking; D019966:Substance-Related Disorders / Q000235:genetics*
references: JAMA Psychiatry. 2013 Oct;70(10):1076-83
references: 23965950
references: J Am Acad Child Adolesc Psychiatry. 2013 Oct;52(10):1048-1056.e3
references: 24074471
references: Nat Genet. 2013 Oct;45(10):1150-9
references: 23974872
references: Hum Genet. 2013 Oct;132(10):1141-51
references: 23743675
references: Behav Genet. 2013 Sep;43(5):363-73
references: 23942779
references: Addict Biol. 2013 Sep;18(5):846-50
references: 22823124
references: Am J Med Genet. 2000 Oct 9;96(5):684-95
references: 11054778
references: J Abnorm Psychol. 2002 Aug;111(3):411-24
references: 12150417
references: Alcohol Res Health. 2002;26(3):214-8
references: 12875050
references: Arch Gen Psychiatry. 2005 Sep;62(9):1042-51
references: 16143736
references: Hum Mol Genet. 2007 Jan 1;16(1):24-35
references: 17158188
references: Twin Res Hum Genet. 2006 Dec;9(6):941-9
references: 17254434
references: Am J Hum Genet. 2007 Sep;81(3):559-75
references: 17701901
references: J Am Acad Child Adolesc Psychiatry. 2008 Feb;47(2):165-73
references: 18176333
references: Arch Gen Psychiatry. 2008 Mar;65(3):345-55
references: 18316681
references: Drug Alcohol Depend. 2008 May 1;95(1-2):14-22
references: 18243582
references: Alcohol Alcohol. 2008 Sep-Oct;43(5):505-15
references: 18477577
references: Bioinformatics. 2008 Dec 15;24(24):2938-9
references: 18974171
references: Arch Gen Psychiatry. 2009 Jul;66(7):773-84
references: 19581569
references: Genet Epidemiol. 2009 Dec;33(8):700-9
references: 19333968
references: Am J Hum Genet. 2010 Feb 12;86(2):113-25
references: 20060087
references: Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5082-7
references: 20202923
references: Nat Genet. 2010 May;42(5):448-53
references: 20418888
references: Nat Genet. 2010 May;42(5):436-40
references: 20418889
references: Nat Genet. 2010 May;42(5):441-7
references: 20418890
references: Alcohol Clin Exp Res. 2010 May;34(5):840-52
references: 20201924
references: Am J Hum Genet. 2010 Jul 9;87(1):139-45
references: 20598278
references: Psychiatr Genet. 2010 Oct;20(5):207-14
references: 20520587
references: Am J Hum Genet. 2011 Jan 7;88(1):76-82
references: 21167468
references: Am J Hum Genet. 2011 Mar 11;88(3):294-305
references: 21376301
references: Hum Hered. 2011;71(1):67-82
references: 21474944
references: Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):7119-24
references: 21471458
references: Addict Biol. 2011 Jul;16(3):514-8
references: 21668797
references: Behav Genet. 2011 Jul;41(4):459-75
references: 21153693
references: Mol Psychiatry. 2011 Aug;16(8):800-8
references: 20585324
references: Addict Biol. 2012 Jan;17(1):171-80
references: 22004471
references: Mol Psychiatry. 2012 Jan;17(1):2-3
references: 21826059
references: Psychol Med. 2012 Mar;42(3):607-16
references: 21854684
references: Bioinformatics. 2012 Jul 1;28(13):1797-9
references: 22513993
references: Transl Psychiatry. 2011;1:e49
references: 22833195
references: PLoS One. 2012;7(10):e45086
references: 23077488
references: Am J Psychiatry. 2012 Oct;169(10):1073-81
references: 22983309
references: Mol Psychiatry. 2013 Jan;18(1):2-3
references: 22614290
references: Twin Res Hum Genet. 2012 Dec;15(6):767-74
references: 23363460
references: Science. 2013 Jun 21;340(6139):1467-71
references: 23722424
references: Nat Genet. 2000 May;25(1):25-9
references: 10802651
references: Biol Psychiatry. 2014 Jul 1;76(1):66-74
references: 24143882
references: Mol Psychiatry. 2014 Jun;19(6):717-23
references: 23958962
references: Mol Psychiatry. 2014 Jan;19(1):41-9
references: 24166409
references: Mol Psychiatry. 2013 Nov;18(11):1218-24
references: 23089632