Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder

Malik Nassan, Paul E. Croarkin, Joan L. Luby, Marin Veldic, Paramjit T. Joshi, Susan L. Mcelroy, Robert M. Post, John T. Walkup, Kelly Cercy, Jennifer R. Geske, Karen Wagner, Alfredo B. Cuellar-Barboza, Leah Casuto, Catharina Lavebratt, Martin Schalling, Peter S. Jensen, Joanna M. Biernacka, Mark A. Frye

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objectives: 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.

Original languageEnglish (US)
Pages (from-to)645-652
Number of pages8
JournalBipolar Disorders
Volume17
Issue number6
DOIs
StatePublished - Sep 1 2015

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Brain-Derived Neurotrophic Factor
Bipolar Disorder
Odds Ratio
Alleles
Age of Onset
Quality Control
Logistic Models

Keywords

  • Association
  • BDNF
  • Bipolar disorder
  • Brain-derived neurotrophic factor
  • Early onset
  • Val66Met

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Nassan, M., Croarkin, P. E., Luby, J. L., Veldic, M., Joshi, P. T., Mcelroy, S. L., ... Frye, M. A. (2015). Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder. Bipolar Disorders, 17(6), 645-652. https://doi.org/10.1111/bdi.12323

Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder. / Nassan, Malik; Croarkin, Paul E.; Luby, Joan L.; Veldic, Marin; Joshi, Paramjit T.; Mcelroy, Susan L.; Post, Robert M.; Walkup, John T.; Cercy, Kelly; Geske, Jennifer R.; Wagner, Karen; Cuellar-Barboza, Alfredo B.; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S.; Biernacka, Joanna M.; Frye, Mark A.

In: Bipolar Disorders, Vol. 17, No. 6, 01.09.2015, p. 645-652.

Research output: Contribution to journalArticle

Nassan, M, Croarkin, PE, Luby, JL, Veldic, M, Joshi, PT, Mcelroy, SL, Post, RM, Walkup, JT, Cercy, K, Geske, JR, Wagner, K, Cuellar-Barboza, AB, Casuto, L, Lavebratt, C, Schalling, M, Jensen, PS, Biernacka, JM & Frye, MA 2015, 'Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder', Bipolar Disorders, vol. 17, no. 6, pp. 645-652. https://doi.org/10.1111/bdi.12323
Nassan, Malik ; Croarkin, Paul E. ; Luby, Joan L. ; Veldic, Marin ; Joshi, Paramjit T. ; Mcelroy, Susan L. ; Post, Robert M. ; Walkup, John T. ; Cercy, Kelly ; Geske, Jennifer R. ; Wagner, Karen ; Cuellar-Barboza, Alfredo B. ; Casuto, Leah ; Lavebratt, Catharina ; Schalling, Martin ; Jensen, Peter S. ; Biernacka, Joanna M. ; Frye, Mark A. / Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder. In: Bipolar Disorders. 2015 ; Vol. 17, No. 6. pp. 645-652.
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abstract = "Objectives: 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.",
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AU - Luby, Joan L.

AU - Veldic, Marin

AU - Joshi, Paramjit T.

AU - Mcelroy, Susan L.

AU - Post, Robert M.

AU - Walkup, John T.

AU - Cercy, Kelly

AU - Geske, Jennifer R.

AU - Wagner, Karen

AU - Cuellar-Barboza, Alfredo B.

AU - Casuto, Leah

AU - Lavebratt, Catharina

AU - Schalling, Martin

AU - Jensen, Peter S.

AU - Biernacka, Joanna M.

AU - Frye, Mark A.

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