COMT and MAO-A Polymorphisms and Obsessive-Compulsive Disorder: A Family-Based Association Study

ObjectiveObsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. the catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013) in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. in an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design.MethodsTransmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A) in 783 OCD trios (probands and their parents). Four different OCD phenotypes (from narrow to broad OCD definitions) and a SNP x SNP epistasis were also analyzed.ResultsOCD, broad and narrow phenotypes, were not associated with any of the investigated COMT and MAO-A polymorphisms. in addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A.ConclusionsThe findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. the evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders.Brazilian governmental agenciesConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundo de Aprimoramento Academico (FUAA-Grant for Academic Improvement)Department of Psychiatry University of São Paulo School of MedicineUniv São Paulo, Fac Med, Dept & Inst Psychiat, São Paulo, SP, BrazilUniv Fed Bahia, Serv Med Univ, Salvador, BA, BrazilUniv Pernambuco, Fac Ciencias Med, Recife, PE, BrazilUniversidade Federal de São Paulo, São Paulo, SP, BrazilBritish Columbia Mental Hlth & Addict Res Inst, Vancouver, BC, CanadaMassachusetts Gen Hosp, PNGU, Boston, MA 02114 USAMassachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USAUniv Calif San Francisco, Dept Psychiat, San Francisco, CA USAHosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, CanadaUniv Michigan, Dept Psychiat, Ann Arbor, MI 48109 USASunnybrook Hlth Sci Ctr, Frederick W Thompson Anxiety Disorders Ctr, Toronto, ON M4N 3M5, CanadaUniv Toronto, Ctr Addict & Mental Hlth, Toronto, ON, CanadaUniv Fed Rio de Janeiro, Inst Psiquiatria, IPUB, Programa Ansiedade & Depressao, Rio de Janeiro, BrazilUniv São Paulo, Inst Math & Stat, Dept Stat, São Paulo, SP, BrazilUniversidade Federal de São Paulo, São Paulo, SP, BrazilCNPq: 573974/2008-0FAPESP: 2005/55628-08FAPESP: 2008/57896-8Web of Scienc

Catechol-<i>O</i>-methyltransferase haplotype blocks composed by single nucleotide polymorphisms evaluated.

<p>Two haplotype blocks, with two SNPs each, were defined in Cathecol-<i>O</i>-methyltransferase. Block 1 comprises SNP rs737866 and rs933271 and Block 2 comprises SNPs rs4646316 and rs165774. Darker squares mean the high D prime and high LOD scores. Haplotype blocks were defined with D prime scores higher than 95. When D prime is 100, the number is not shown inside the square. Two haplotype blocks, with two SNPs each, were defined in Cathecol-<i>O</i>-methyltransferase. Data shown in the table refers to each haplotypes allele combination association results.</p