Manuel Mattheisen

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

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  • Menxing Li, Institut for Læring og Filosofi, Denmark
  • X-J Luo
  • ,
  • M Rietschel
  • ,
  • C M Lewis
  • ,
  • Manuel Mattheisen
  • B Müller-Myhsok
  • ,
  • S Jamain
  • ,
  • M Leboyer
  • ,
  • M Landén
  • ,
  • P M Thompson
  • ,
  • S Cichon
  • ,
  • M M Nöthen
  • ,
  • T G Schulze
  • ,
  • Neal P Sullivan, Department of Chemical and Biochemical Engineering, Denmark
  • S E Bergen
  • ,
  • G Donohoe
  • ,
  • D W Morris
  • ,
  • A Hargreaves
  • ,
  • M Gill
  • ,
  • A Corvin
  • ,
  • C Hultman
  • ,
  • A W Toga
  • ,
  • Lijuan Shi, Kemisk Institut, Denmark
  • 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
  • ,
  • Jonathan Stein, 2012 Institut for Farmakologi og Farmakoterapi, Denmark
  • S E Medland
  • ,
  • A Arias Vasquez
  • ,
  • D P Hibar
  • ,
  • B Franke
  • ,
  • N G Martin
  • ,
  • M J Wright
  • ,
  • B Su
  • ,
  • MooDS Bipolar Consortium
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 rs6785[A], 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
JournalMolecular Psychiatry
ISSN1359-4184
DOIs
Publication statusPublished - 9 Apr 2013
Externally publishedYes

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