Test of association between GABRA2 (SNP rs279871) and adolescent conduct/alcohol use disorders utilizing a sample of clinic referred youth with serious substance and conduct problems, controls and available first degree relatives.
Recent findings have linked the GABRA2 gene with antisocial personality disorder and alcohol dependence (AD) in adults and conduct disorder (CD), but not AD symptoms, in children and adolescents. We sought to replicate previous findings and test for an association between a single nucleotide polymorphism (SNP) in the GABRA2 gene (rs279871) and CD among adolescents.


METHODS
Adolescent patients (n=371), 13-18 years old, were recruited from a university substance abuse treatment program. Patient siblings (n=245), parents of patients (n=355), adolescent controls (n=185), siblings of controls (n=163) and parents of controls (n=263) were included in these analyses (total sample n=1582). Case-control (using only Caucasian and Hispanic probands) and family-based association tests were completed to test for association between rs279871 and several a priori CD and AD phenotypes.


RESULTS
For case-control association tests, rs279871 was significantly associated with CD (p=0.02) but not AD phenotypes; the result did not survive strict correction for multiple testing. All family-based association tests were non-significant (CD p=0.48; CD symptom count age corrected within sex p=0.91; AD p=0.84; alcohol use disorder p=0.52).


CONCLUSIONS
Consistent with previous findings, the results do not support the association between GABRA2 SNP rs279871 and AD in adolescents. Our results also do not support an association between rs279871 and CD; the study limitations are reviewed.
Division of Substance Dependence, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA. joseph.sakai@ucdenver.edu
Joseph T
JT
Sakai
Michael C
MC
Stallings
Thomas J
TJ
Crowley
Heather L
HL
Gelhorn
Matthew B
MB
McQueen
Marissa A
MA
Ehringer
D000293:Adolescent; D000428:Alcohol Drinking / Q000235:genetics*; D000437:Alcoholism / Q000150:complications / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005190:Family; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000235:genetics / Q000534:rehabilitation; D009679:Nuclear Family; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D000297:Psychology, Adolescent; D011963:Receptors, GABA-A / Q000235:genetics*; D035781:Siblings; D019966:Substance-Related Disorders / Q000150:complications / Q000235:genetics / Q000534:rehabilitation
C484841:GABRA2 protein, human; D011963:Receptors, GABA-A