Article
Genome wide association study on nicotine dependence
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Authors
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Kirstin Mittelstraß
- GSF-Forschungszentrum für Umwelt und Gesundheit, 85764 Neuherberg
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Georg Winterer
- University of Düsseldorf, 40629 Düsseldorf
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Norman Klopp
- GSF-Forschungszentrum für Umwelt und Gesundheit, 85764 Neuherberg
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Thomas Illig
- GSF-Forschungszentrum für Umwelt und Gesundheit, 85764 Neuherberg
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Hermann Brenner
- DKFZ-Deutsches Krebsforschungszentrum, 69115 Heidelberg
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Lutz Breitling
- DKFZ-Deutsches Krebsforschungszentrum, 69115 Heidelberg
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Andreas Gal
- University of Hamburg Medical Center Eppendorf, 22529 Hamburg
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Dan Rujescu
- LMU-München, 80336 München
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Heinz-Erich Wichmann
- GSF-Forschungszentrum für Umwelt und Gesundheit, 85764 Neuherberg
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Norbert Dahmen
- University of Mainz, 55131 Mainz
| Published: | September 6, 2007 |
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Outline
Text
The aim of the study is to identify DNA variants being associated with nicotine-related behaviour. Nicotine dependence is the leading preventable cause of death and morbidity causing a huge public health problem. The World Health Organization (WHO) estimates that 150 million people currently alive will die from their tobacco use in the next 25 years. Although environmental factors, such as peer smoking and tobacco industry advertising are clearly important in smoking initiation [Ref. 6], there is abundant evidence for a genetic component. There are both overlapping and unique genetic influences on smoking initiation, nicotine dependence, and smoking persistence [Ref. 2], [Ref. 3], [Ref. 4]. In a summary of data, Sullivan and Kendler [Ref. 5] estimated that additive genetic effects account for 56% of the variance in liability to initiate smoking. A genetic component has also been found for age at smoking onset [Ref. 1]. There is also a genetic component for smoking persistence in different age groups [Ref. 4].
In a first step of this project, 1,644 subjects in the age range of 45 to 69 years of the KORA S3/F3 cohort were genotyped by Affymetrix 500K chips. The resulting SNPs were classified according to the quantity of nicotine consumption and other relevant phenotypes such as the Fagerstrom Test for Nicotine Dependence (FTND).
Based on strength of association with nicotine consumption and knowledge about potential pathways 1500 SNPs were chosen for validation. These SNPs are currently being genotyped in an independent cohort of 1400 persons of the KORA S3/F3 and S4 studies as a first control filter using the Illumina Golden Gate technique. Significantly associated SNPs will be replicated and assessed for specificity in well characterized clinical samples and also analysed in respect to intermediate phenotypes.
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