title: Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.
abstract: OBJECTIVE
  Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association.
  
  
  METHODS
  DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects.
  
  
  RESULTS
  Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04).
  
  
  CONCLUSIONS
  These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder.
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Malik
authors.initials: M
authors.lastname: Nassan
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Croarkin
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Joan L
authors.initials: JL
authors.lastname: Luby
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Marin
authors.initials: M
authors.lastname: Veldic
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Children's National Medical Center, Washington, DC, USA.
authors.forename: Paramjit T
authors.initials: PT
authors.lastname: Joshi
authors.affiliation: Linder Center of HOPE, Mason, OH, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: McElroy
authors.affiliation: Bipolar Collaborative Network, Bethesda, MD, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Post
authors.affiliation: Department of Psychiatry, Weil Cornell Medical College, New York, NY, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Walkup
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Cercy
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Geske
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Wagner
authors.affiliation: Universidad Autonoma de Nuevo Leon, Neuvo Leon, Mexico.
authors.forename: Alfredo B
authors.initials: AB
authors.lastname: Cuellar-Barboza
authors.affiliation: Linder Center of HOPE, Mason, OH, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Casuto
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.|Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Catharina
authors.initials: C
authors.lastname: Lavebratt
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.|Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
authors.affiliation: The REACH Institute, New York, NY, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Jensen
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.|Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Biernacka
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D014481:United States
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: BDNF; Val66Met; association; bipolar disorder; brain-derived neurotrophic factor; early onset