title: Variants in estrogen receptor alpha gene are associated with phenotypical expression of obsessive-compulsive disorder.
abstract: Compelling data from animal and clinical studies suggest that sex steroids may play a role in the etiopathology of obsessive-compulsive disorder (OCD). The aim of this study was to investigate whether variants in estrogen receptor genes ESR1 and ESR2 may contribute to the genetic susceptibility to OCD, through a case-control association study using an extensive linkage disequilibrium-mapping approach. Twenty tag single-nucleotide polymorphisms (tagSNPs) covering the ESR2 region and nine tagSNPS from regions of ESR1 reported to be related to transcriptional control were genotyped in 229 OCD patients and 279 controls. SNP association and haplotype analysis were performed. The association of these genes and OCD subphenotypes was tested, considering early-onset OCD, comorbid tic and affective disorders, and OCD symptom dimensions. No significant difference in the distribution of alleles or genotypes was detected between controls and OCD subjects. Nevertheless, on analyzing OCD subphenotypes, SNP rs34535804 in ESR1 and a five SNPs haplotype, located at the 5' end of intron 1 of ESR1, were associated with the presence of contamination obsessions and cleaning compulsions. Specifically, carriers of the ACCCG haplotype, a combination of functional alleles related to higher ER alpha expression, showed a reduced risk of suffering from these symptoms. Our results suggest that the ESR1 gene may contribute to the genetic vulnerability to certain OCD manifestations. The dissection of OCD into more homogeneous subphenotypes may well help to identify susceptibility genes for the disorder.
authors.affiliation: OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain. mpalonso@bellvitgehospital.cat
authors.forename: P
authors.initials: P
authors.lastname: Alonso
authors.forename: M
authors.initials: M
authors.lastname: Gratacòs
authors.forename: C
authors.initials: C
authors.lastname: Segalàs
authors.forename: G
authors.initials: G
authors.lastname: Escaramís
authors.forename: E
authors.initials: E
authors.lastname: Real
authors.forename: M
authors.initials: M
authors.lastname: Bayés
authors.forename: J
authors.initials: J
authors.lastname: Labad
authors.forename: A
authors.initials: A
authors.lastname: Pertusa
authors.forename: J
authors.initials: J
authors.lastname: Vallejo
authors.forename: X
authors.initials: X
authors.lastname: Estivill
authors.forename: J M
authors.initials: JM
authors.lastname: Menchón
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D055815:Young Adult
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha