Association of the cannabinoid receptor gene (CNR1) with ADHD and post-traumatic stress disorder.
Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder affecting some 5-10% of children and 4-5% of adults. The cannabinoid receptor gene (CNR1) is a positional candidate gene due to its location near an identified ADHD linkage peak on chromosome 6, its role in stress and dopamine regulation, its association with other psychiatric disorders that co-occur with ADHD, and its function in learning and memory. We tested SNP variants at the CNR1 gene in two independent samples-an unselected adolescent sample from Northern Finland, and a family-based sample of trios (an ADHD child and their parents). In addition to using the trios for association study, the parents (with and without ADHD) were used as an additional case/control sample of adults for association tests. ADHD and its co-morbid psychiatric disorders were examined. A significant association was detected for a SNP haplotype (C-G) with ADHD (P = 0.008). A sex by genotype interaction was observed as well with this haplotype posing a greater risk in males than females. An association of an alternative SNP haplotype in this gene was found for post-traumatic stress disorder (PTSD) (P = 0.04 for C-A, and P = 0.01 for C-G). These observations require replication, however, they suggest that the CNR1 gene may be a risk factor for ADHD and possibly PTSD, and that this gene warrants further investigation for a role in neuropsychiatric disorders.
Lu
Ake T
AT
Department of Human Genetics, University of California, Los Angeles, California, USA.
Ogdie
Matthew N
MN
Järvelin
Marjo-Ritta
MR
Moilanen
Irma K
IK
Loo
Sandra K
SK
McCracken
James T
JT
McGough
James J
JJ
Yang
May H
MH
Peltonen
Leena
L
Nelson
Stanley F
SF
Cantor
Rita M
RM
Smalley
Susan L
SL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D015141:Los Angeles / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010290:Parents; D020641:Polymorphism, Single Nucleotide; D043882:Receptors, Cannabinoid / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors; D035781:Siblings; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics*
D043882:Receptors, Cannabinoid