title: COMT and MAO-A polymorphisms and obsessive-compulsive disorder: a family-based association study.
abstract: OBJECTIVE
  Obsessive-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.
  
  
  METHODS
  Transmission 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.
  
  
  RESULTS
  OCD, 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.
  
  
  CONCLUSIONS
  The 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.
authors: Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil; Serviço Médico Universitário, Universidade Federal da Bahia (UFBA, Federal University of Bahia), Salvador, BA, Brazil.
authors: Aline Santos
authors: AS
authors: Sampaio
authors: Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Ana Gabriela
authors: AG
authors: Hounie
authors: Universidade de Pernambuco (UPE, University of Pernambuco) Faculdade de Ciências Médicas, Recife, PE, Brazil.
authors: Kátia
authors: K
authors: Petribú
authors: Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Carolina
authors: C
authors: Cappi
authors: Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Ivanil
authors: I
authors: Morais
authors: Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Homero
authors: H
authors: Vallada
authors: Universidade Federal de Sao Paulo (UNIFESP, Federal University of São Paulo), São Paulo, SP, Brazil.
authors: Maria Conceição
authors: MC
authors: do Rosário
authors: British Columbia Mental Health and Addictions Research Institute, Vancouver, BC, Canada; Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: S Evelyn
authors: SE
authors: Stewart
authors: Center for Human Genetics Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: Jesen
authors: J
authors: Fargeness
authors: Department of Psychiatry, University of California, San Francisco, California, United States of America.
authors: Carol
authors: C
authors: Mathews
authors: Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Paul
authors: P
authors: Arnold
authors: Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Gregory L
authors: GL
authors: Hanna
authors: The Frederick W. Thompson Anxiety Disorders Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors: Margaret
authors: M
authors: Richter
authors: Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors: James
authors: J
authors: Kennedy
authors: Programa de Ansiedade e Depressão, Instituto de Psiquiatria, Universidade Federal do Rio de Janeiro (IPUB/UFRJ), Rio de Janeiro, RJ, Brazil.
authors: Leonardo
authors: L
authors: Fontenelle
authors: Department of Statistics, The Institute of Mathematics and Statistics, University of São Paulo, SP, Brazil.
authors: Carlos Alberto
authors: CA
authors: de Bragança Pereira
authors: Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: David L
authors: DL
authors: Pauls
authors: Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Eurípedes Constantino
authors: EC
authors: Miguel
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D004843:Epistasis, Genetic; D005190:Family; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D009771:Obsessive-Compulsive Disorder / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase