The Bipolar Association Case-Control Study (BACCS) and Meta-Analysis: No Association With the 5,10-Methylenetetrahydrofolate Reductase Gene and Bipolar Disorder

Research output: Contribution to journalArticle


  • S Cohen-Woods
  • I Craig
  • D Gaysina
  • J Gray
  • C Gunasinghe
  • N Craddock
  • A Elkin
  • J Kennedy
  • N King
  • A Korszun
  • J Knight
  • M Owen
  • S Parikh
  • J Strauss
  • A Sterne
  • F Tozzi
  • J Perry
  • P Muglia
  • J Vincent
  • P McGuffin
  • A Farmer


Bipolar disorder (BD) is a complex genetic disease for which the underlying pathophysiology has yet to be fully explained. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in folate-mediated one-carbon metabolism and folate deficiency can be associated with psychiatric symptoms. A single base variant in MTHFR gene (C677T) results in the production of a mildly dysfunctional thermolabile enzyme and has recently been implicated in BD. We conducted an association study of this polymorphism in 897 patients with bipolar I or bipolar II disorder, and 1,687 healthy control subjects. We found no evidence for genotypic or allelic association in this sample. We also performed a meta-analysis of our own, and all published data, and report no evidence for association. Our findings suggest that the MTHFR C677T polymorphism is not involved in the genetic etiology of clinically significant BD. (c) 2010 Wiley-Liss, Inc.


Original languageEnglish
Pages (from-to)1298-1304
Number of pages7
JournalAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Issue number7
Publication statusPublished - 1 Oct 2010


  • genetics, MTHFR, bipolar disorder, mood disorder, manic depression