Obsessive-compulsive disorder (OCD) is characterized by recurring obsessions and/or compulsions and has been estimated to affect nearly 5 million people in the United States (Karno et al., 1988). Evidence for a strong genetic component in OCD comes from ... Obsessive-compulsive disorder (OCD) is characterized by recurring obsessions and/or compulsions and has been estimated to affect nearly 5 million people in the United States (Karno et al., 1988). Evidence for a strong genetic component in OCD comes from twin studies, family genetics studies, and segregation analyses, as reviewed by Alsobrook et al. (2002). Zhang et al. (2002) suggested that hoarding is likely to be an evolutionarily conserved trait that, in times of adversity, was associated with increased survival and reproductive fitness. However, extreme forms of this trait are associated with marked disability and poor response to treatment (Black et al., 1998; Mataix-Cols et al., 1999).
Karayiorgou et al. (1997, 1999) found an association between OCD and catechol-O-methyltransferase (COMT; 116790); the homozygous low activity genotype of the COMT gene was associated with risk for OCD in males. Alsobrook et al. (2002) used a family-based ... Karayiorgou et al. (1997, 1999) found an association between OCD and catechol-O-methyltransferase (COMT; 116790); the homozygous low activity genotype of the COMT gene was associated with risk for OCD in males. Alsobrook et al. (2002) used a family-based genetic design in haplotype relative risk (HRR) and transmission-disequilibrium (TDT) analyses of the association between OCD and COMT. Fifty-six OCD probands and their parents were genotyped for the COMT locus. Analysis of allele and genotype frequencies between the proband genotypes and the control (parental nontransmitted) genotypes failed to replicate the previous finding of gender divergence and gave no evidence of overall association; furthermore, no linkage was detected by TDT. However, further analysis of the COMT allele frequencies by proband gender gave evidence of a mildly significant association with the low activity COMT allele in female probands (p = 0.049), but not in male probands. Walitza et al. (2002) performed an association analysis of the -1438G-A promoter polymorphism in the HTR2A gene (182135.0002) in 55 children and adolescents with OCD and in 223 controls consisting of unrelated students. Statistically significant differences in genotype (p less than 0.05) and allele frequencies (p less than 0.05) were observed that suggested an association of the -1438A allele with OCD. Ozaki et al. (2003) described association between an ile425-to-val (I425V; 182138.0002) polymorphism of the serotonin transporter gene (SLC6A4) and OCD and some other 'serotonin-related disorders' in 2 unrelated families. Of 7 family members with the mutation, 6 had OCD and 1 had obsessive-compulsive personality disorder; several of them also met diagnostic criteria for other disorders, including Asperger syndrome (see 608638), social phobia, anorexia nervosa (see 606788), tic disorder, and alcohol (103780) and other substance abuse/dependence. The 4 most clinically affected individuals had both the I425V mutation and the L allele of SLC6A4 (182138.0001), suggesting a gene dose effect given that the L allele transcribes more efficiently. Hu et al. (2006) found that the gain-of-function homozygous L(A)L(A) genotype of SLC6A4 was approximately twice as common in 169 whites with obsessive-compulsive disorder than in 253 ethnically matched controls. Hu et al. (2006) performed a replication study in 175 trios consisting of probands with OCD and their parents. The L(A) allele was 2-fold overtransmitted to the patients with OCD. The SLC6A4 L(A)L(A) genotype exerted a moderate (1.8-fold) effect on risk of OCD, thus establishing a role for the HTT gene in OCD. For a possible association between variation in expression of the NTRK3 gene and hoarding, see 191316.