2. Academic Validation
  3. COMT and MAO-A polymorphisms and obsessive-compulsive disorder: a family-based association study

COMT and MAO-A polymorphisms and obsessive-compulsive disorder: a family-based association study

  • PLoS One. 2015 Mar 20;10(3):e0119592. doi: 10.1371/journal.pone.0119592.
Aline Santos Sampaio 1,  Ana Gabriela Hounie 2,  Kátia Petribú 3,  Carolina Cappi 2,  Ivanil Morais 2,  Homero Vallada 2,  Maria Conceição do Rosário 4,  S Evelyn Stewart 5,  Jesen Fargeness 6,  Carol Mathews 7,  Paul Arnold 8,  Gregory L Hanna 9,  Margaret Richter 10,  James Kennedy 11,  Leonardo Fontenelle 12,  Carlos Alberto de Bragança Pereira 13,  David L Pauls 14,  Eurípedes Constantino Miguel 2
Affiliations

Affiliations

  • 1 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.
  • 2 Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
  • 3 Universidade de Pernambuco (UPE, University of Pernambuco) Faculdade de Ciências Médicas, Recife, PE, Brazil.
  • 4 Universidade Federal de Sao Paulo (UNIFESP, Federal University of São Paulo), São Paulo, SP, Brazil.
  • 5 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.
  • 6 Center for Human Genetics Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
  • 7 Department of Psychiatry, University of California, San Francisco, California, United States of America.
  • 8 Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • 9 Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, United States of America.
  • 10 The Frederick W. Thompson Anxiety Disorders Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
  • 11 Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
  • 12 Programa de Ansiedade e Depressão, Instituto de Psiquiatria, Universidade Federal do Rio de Janeiro (IPUB/UFRJ), Rio de Janeiro, RJ, Brazil.
  • 13 Department of Statistics, The Institute of Mathematics and Statistics, University of São Paulo, SP, Brazil.
  • 14 Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, Massachusetts, United States of America.
PMID: 25793616 DOI: 10.1371/journal.pone.0119592
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.

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