title: Externalizing behaviors are associated with SNPs in the CHRNA5/CHRNA3/CHRNB4 gene cluster.
abstract: There is strong evidence for shared genetic factors contributing to childhood externalizing disorders and substance abuse. Externalizing disorders often precede early substance experimentation, leading to the idea that individuals inherit a genetic vulnerability to generalized disinhibitory psychopathology. Genetic variation in the CHRNA5/CHRNA3/CHRNB4 gene cluster has been associated with early substance experimentation, nicotine dependence, and other drug behaviors. This study examines whether the CHRNA5/CHRNA3/CHRNB4 locus is correlated also with externalizing behaviors in three independent longitudinally assessed adolescent samples. We developed a common externalizing behavior phenotype from the available measures in the three samples, and tested for association with 10 SNPs in the gene cluster. Significant results were detected in two of the samples, including rs8040868, which remained significant after controlling for smoking quantity. These results expand on previous work focused mainly on drug behaviors, and support the hypothesis that variation in the CHRNA5/CHRNA3/CHRNB4 locus is associated with early externalizing behaviors.
authors: Department of Integrative Physiology, University of Colorado-Boulder, CO 80309, USA.
authors: Sarah H
authors: SH
authors: Stephens
authors: Nicole R
authors: NR
authors: Hoft
authors: Isabel R
authors: IR
authors: Schlaepfer
authors: Susan E
authors: SE
authors: Young
authors: Robin C
authors: RC
authors: Corley
authors: Matthew B
authors: MB
authors: McQueen
authors: Christian
authors: C
authors: Hopfer
authors: Thomas
authors: T
authors: Crowley
authors: Michael
authors: M
authors: Stallings
authors: John
authors: J
authors: Hewitt
authors: Marissa A
authors: MA
authors: Ehringer
mesh_terms: D000293:Adolescent; D002653:Child Behavior Disorders / Q000235:genetics* / Q000523:psychology; D005190:Family; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D005810:Multigene Family / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000235:genetics / Q000523:psychology; D019966:Substance-Related Disorders / Q000235:genetics* / Q000523:psychology
chemical_list: D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human; C447159:CHRNB4 protein, human