Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility

M. Li, X. J. Luo, M. Rietschel, C. M. Lewis, M. Mattheisen, B. Müller-Myhsok, S. Jamain, M. Leboyer, M. Landén, P. M. Thompson, S. Cichon, M. M. Nöthen, T. G. Schulze, P. F. Sullivan, S. E. Bergen, G. Donohoe, D. W. Morris, A. Hargreaves, M. Gill, A. Corvin & 28 others C. Hultman, A. W. Toga, L. Shi, Q. Lin, H. Shi, L. Gan, A. Meyer-Lindenberg, D. Czamara, C. Henry, B. Etain, J. C. Bis, M. A. Ikram, M. Fornage, S. Debette, L. J. Launer, S. Seshadri, S. Erk, H. Walter, A. Heinz, F. Bellivier, J. L. Stein, S. E. Medland, A. Arias Vasquez, D. P. Hibar, B. Franke, N. G. Martin, M. J. Wright, B. Su

Research output: Contribution to journalArticle

Abstract

Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64 888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785A, P=6.32 × 10 -5, odds ratio (OR)=1.090). Risk SNPs were then subjected to further analyses in healthy Europeans for intermediate phenotypes of BD, including hippocampal volume, hippocampal function and cognitive performance. Our results showed that the risk SNPs were significantly associated with hippocampal volume and hippocampal function, with the risk alleles showing a decreased hippocampal volume and diminished activation of the left hippocampus, adding further evidence for their involvement in BD susceptibility. We also found the risk SNPs were strongly associated with CREB1 expression in lymphoblastoid cells (P

Original languageEnglish (US)
Pages (from-to)452-461
Number of pages10
JournalMolecular Psychiatry
Volume19
Issue number4
DOIs
StatePublished - Apr 2014
Externally publishedYes

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Gene Expression Regulation
Bipolar Disorder
Single Nucleotide Polymorphism
Major Depressive Disorder
Phenotype
Cognition
Genes
Hippocampus
Alleles
Odds Ratio

Keywords

  • Association
  • Bipolar disorder
  • CREB1
  • Gene expression
  • Intermediate phenotype
  • Natural selection

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility. / Li, M.; Luo, X. J.; Rietschel, M.; Lewis, C. M.; Mattheisen, M.; Müller-Myhsok, B.; Jamain, S.; Leboyer, M.; Landén, M.; Thompson, P. M.; Cichon, S.; Nöthen, M. M.; Schulze, T. G.; Sullivan, P. F.; Bergen, S. E.; Donohoe, G.; Morris, D. W.; Hargreaves, A.; Gill, M.; Corvin, A.; Hultman, C.; Toga, A. W.; Shi, L.; Lin, Q.; Shi, H.; Gan, L.; Meyer-Lindenberg, A.; Czamara, D.; Henry, C.; Etain, B.; Bis, J. C.; Ikram, M. A.; Fornage, M.; Debette, S.; Launer, L. J.; Seshadri, S.; Erk, S.; Walter, H.; Heinz, A.; Bellivier, F.; Stein, J. L.; Medland, S. E.; Arias Vasquez, A.; Hibar, D. P.; Franke, B.; Martin, N. G.; Wright, M. J.; Su, B.

In: Molecular Psychiatry, Vol. 19, No. 4, 04.2014, p. 452-461.

Research output: Contribution to journalArticle

Li, M, Luo, XJ, Rietschel, M, Lewis, CM, Mattheisen, M, Müller-Myhsok, B, Jamain, S, Leboyer, M, Landén, M, Thompson, PM, Cichon, S, Nöthen, MM, Schulze, TG, Sullivan, PF, Bergen, SE, Donohoe, G, Morris, DW, Hargreaves, A, Gill, M, Corvin, A, Hultman, C, Toga, AW, Shi, L, Lin, Q, Shi, H, Gan, L, Meyer-Lindenberg, A, Czamara, D, Henry, C, Etain, B, Bis, JC, Ikram, MA, Fornage, M, Debette, S, Launer, LJ, Seshadri, S, Erk, S, Walter, H, Heinz, A, Bellivier, F, Stein, JL, Medland, SE, Arias Vasquez, A, Hibar, DP, Franke, B, Martin, NG, Wright, MJ & Su, B 2014, 'Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility', Molecular Psychiatry, vol. 19, no. 4, pp. 452-461. https://doi.org/10.1038/mp.2013.37
Li, M. ; Luo, X. J. ; Rietschel, M. ; Lewis, C. M. ; Mattheisen, M. ; Müller-Myhsok, B. ; Jamain, S. ; Leboyer, M. ; Landén, M. ; Thompson, P. M. ; Cichon, S. ; Nöthen, M. M. ; Schulze, T. G. ; Sullivan, P. F. ; Bergen, S. E. ; Donohoe, G. ; Morris, D. W. ; Hargreaves, A. ; Gill, M. ; Corvin, A. ; Hultman, C. ; Toga, A. W. ; Shi, L. ; Lin, Q. ; Shi, H. ; Gan, L. ; Meyer-Lindenberg, A. ; Czamara, D. ; Henry, C. ; Etain, B. ; Bis, J. C. ; Ikram, M. A. ; Fornage, M. ; Debette, S. ; Launer, L. J. ; Seshadri, S. ; Erk, S. ; Walter, H. ; Heinz, A. ; Bellivier, F. ; Stein, J. L. ; Medland, S. E. ; Arias Vasquez, A. ; Hibar, D. P. ; Franke, B. ; Martin, N. G. ; Wright, M. J. ; Su, B. / Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility. In: Molecular Psychiatry. 2014 ; Vol. 19, No. 4. pp. 452-461.
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AU - Li, M.

AU - Luo, X. J.

AU - Rietschel, M.

AU - Lewis, C. M.

AU - Mattheisen, M.

AU - Müller-Myhsok, B.

AU - Jamain, S.

AU - Leboyer, M.

AU - Landén, M.

AU - Thompson, P. M.

AU - Cichon, S.

AU - Nöthen, M. M.

AU - Schulze, T. G.

AU - Sullivan, P. F.

AU - Bergen, S. E.

AU - Donohoe, G.

AU - Morris, D. W.

AU - Hargreaves, A.

AU - Gill, M.

AU - Corvin, A.

AU - Hultman, C.

AU - Toga, A. W.

AU - Shi, L.

AU - Lin, Q.

AU - Shi, H.

AU - Gan, L.

AU - Meyer-Lindenberg, A.

AU - Czamara, D.

AU - Henry, C.

AU - Etain, B.

AU - Bis, J. C.

AU - Ikram, M. A.

AU - Fornage, M.

AU - Debette, S.

AU - Launer, L. J.

AU - Seshadri, S.

AU - Erk, S.

AU - Walter, H.

AU - Heinz, A.

AU - Bellivier, F.

AU - Stein, J. L.

AU - Medland, S. E.

AU - Arias Vasquez, A.

AU - Hibar, D. P.

AU - Franke, B.

AU - Martin, N. G.

AU - Wright, M. J.

AU - Su, B.

PY - 2014/4

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