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

Malik Nassan, Paul E Croarkin, Joan L. Luby, Marin D Veldic, Paramjit T. Joshi, Susan L. Mcelroy, Robert M. Post, John T. Walkup, Kelly Cercy, Jennifer R. Geske, Karen D. 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

Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder. / Nassan, Malik; Croarkin, Paul E; Luby, Joan L.; Veldic, Marin D; Joshi, Paramjit T.; Mcelroy, Susan L.; Post, Robert M.; Walkup, John T.; Cercy, Kelly; Geske, Jennifer R.; Wagner, Karen D.; 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, MD, Joshi, PT, Mcelroy, SL, Post, RM, Walkup, JT, Cercy, K, Geske, JR, Wagner, KD, 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 D ; Joshi, Paramjit T. ; Mcelroy, Susan L. ; Post, Robert M. ; Walkup, John T. ; Cercy, Kelly ; Geske, Jennifer R. ; Wagner, Karen D. ; 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 - Nassan, Malik

AU - Croarkin, Paul E

AU - Luby, Joan L.

AU - Veldic, Marin D

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 D.

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

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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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KW - Early onset

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