Universität zu Köln

Winterer, Georg, Mittelstrass, Kirstin, Giegling, Ina, Lamina, Claudia ORCID: 0000-0002-5398-5806, Fehr, Christoph, Brenner, Hermann ORCID: 0000-0002-6129-1572, Breitling, Lutz P., Nitz, Barbara ORCID: 0000-0001-6289-7237, Raum, Elke, Mueller, Heiko, Gallinat, Juergen, Gal, Andreas, Heim, Katharina, Prokisch, Holger ORCID: 0000-0003-2379-6286, Meitinger, Thomas ORCID: 0000-0002-8838-8403, Hartmann, Annette M., Moeller, Hans-Juergen, Gieger, Christian ORCID: 0000-0001-6986-9554, Wichmann, H-Erich, Illig, Thomas, Dahmen, Norbert and Rujescu, Dan (2010). Risk Gene Variants for Nicotine Dependence in the CHRNA5-CHRNA3-CHRNB4 Cluster Are Associated With Cognitive Performance. Am. J. Med. Genet. B, 153B (8). S. 1448 - 1459. HOBOKEN: WILEY. ISSN 1552-485X

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Abstract

Recent studies strongly support an association of the nicotinic acetylcholine receptor gene cluster CHRNA5-CHRNA3-CHRNB4 with nicotine dependence (ND). However, the precise genotype-phenotype relationship is still unknown. Clinical and epidemiological data on smoking behavior raise the possibility that the relevant gene variants may indirectly contribute to the development of ND by affecting cognitive performance in some smokers who consume nicotine for reasons of co nition enhancement.'' Here, we tested seven single nucleotide polymorphisms (SNPs) rs684513, rs637137, rs16969968, rs578776, rs1051730, rs3743078, rs3813567 from the CHRNA5-CHRNA3-CHRNB4 gene cluster for association with ND, measures of cognitive performance and gene expression. As expected, we found all SNPs being associated with ND in three independent cohorts (KORA, NCOOP, ESTHER) comprising 5,561 individuals. In an overlapping sample of 2,186 subjects we found three SNPs (rs16969968, rs1051730, rs3743078) being associated with cognitive domains from the Wechsler-Adult-Intelligence Scale (WAIS-R)-most notably in the performance subtest object assembly'' and the verbal subtest similarities.'' In a refined analysis of a subsample of 485 subjects, two of these three SNPs (rs16969968, rs1051730) were associated with n-back task performance/Continuous Performance Test. Furthermore, two CHRNA5 risk alleles (rs684513, rs637137) were associated with CHRNA5 mRNA expression levels in whole blood in a subgroup of 190 subjects. We here report for the first time an association of CHRNA5-CHRNA3-CHRNB4 gene variants with cognition possibly mediating in part risk for developing ND. The observed phenotype-genotype associations may depend on altered levels of gene expression. (C) 2010 Wiley-Liss, Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Winterer, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Mittelstrass, Kirstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Giegling, Ina UNSPECIFIED UNSPECIFIED UNSPECIFIED Lamina, Claudia UNSPECIFIED orcid.org/0000-0002-5398-5806 UNSPECIFIED Fehr, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Brenner, Hermann UNSPECIFIED orcid.org/0000-0002-6129-1572 UNSPECIFIED Breitling, Lutz P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nitz, Barbara UNSPECIFIED orcid.org/0000-0001-6289-7237 UNSPECIFIED Raum, Elke UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Heiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Gallinat, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Gal, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Heim, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Prokisch, Holger UNSPECIFIED orcid.org/0000-0003-2379-6286 UNSPECIFIED Meitinger, Thomas UNSPECIFIED orcid.org/0000-0002-8838-8403 UNSPECIFIED Hartmann, Annette M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Moeller, Hans-Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Gieger, Christian UNSPECIFIED orcid.org/0000-0001-6986-9554 UNSPECIFIED Wichmann, H-Erich UNSPECIFIED UNSPECIFIED UNSPECIFIED Illig, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Dahmen, Norbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Rujescu, Dan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-491050
DOI:	10.1002/ajmg.b.31126
Journal or Publication Title:	Am. J. Med. Genet. B
Volume:	153B
Number:	8
Page Range:	S. 1448 - 1459
Date:	2010
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1552-485X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENOME-WIDE ASSOCIATION; YOUNG-WOMEN SMOKE; LUNG-CANCER; SUSCEPTIBILITY LOCUS; CIGARETTE-SMOKING; PRION PROTEIN; CHRM2 GENE; FOLLOW-UP; ATTENTION; COMT Multiple languages Genetics & Heredity; Psychiatry Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49105