Association studies of serotonin system candidate genes in early-onset obsessive-compulsive disorder.
BACKGROUND
Family-based evidence for association at serotonin system genes SLC6A4, HTR1B, HTR2A, and brain-derived neurotrophic factor (BDNF) has been previously reported in obsessive-compulsive disorder (OCD). Early-onset OCD is a more familial form of the disorder.


METHODS
We used the transmission-disequilibrium test of association at common polymorphisms in each of these genes in 54 parent-child trios ascertained through probands with early-onset OCD.


RESULTS
No evidence for association was detected at any of the polymorphisms in the entire set of subjects. Nominally significant association was found at the HTR2A rs6311 polymorphism in subjects with tic disorder and OCD (p = .05), replicating a previous finding in Tourette syndrome and OCD. Nominally significant association was also found for the SLC6A4 HT transporter gene-linked polymorphic region (5-HTTLPR) polymorphism for female subjects (p = .03). Neither association would remain significant after statistical correction for multiple testing. Despite no individual study reporting replication, a pooled analysis of five replication studies of the SLC6A4 5-HTTLPR polymorphism supports association (p = .02).


CONCLUSIONS
Low power across individual association studies in OCD may lead to a false acceptance of the null hypothesis. Accumulation of evidence from multiple studies will be necessary to evaluate the potential role for these genes in contributing to susceptibility to OCD.
Dickel
Diane E
DE
Institute of Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.
Veenstra-VanderWeele
Jeremy
J
Bivens
Nancy Chiu
NC
Wu
Xiaolin
X
Fischer
Daniel J
DJ
Van Etten-Lee
Michelle
M
Himle
Joseph A
JA
Leventhal
Bennett L
BL
Cook
Edwin H
EH
Hanna
Gregory L
GL
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000235:genetics* / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012737:Sex Factors; D013981:Tic Disorders / Q000453:epidemiology; D005879:Tourette Syndrome / Q000453:epidemiology / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D004247:DNA