Genome-wide association study in Finnish twins highlights the connection between nicotine addiction and neurotrophin signaling pathway

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Hällfors , J , Palviainen , T , Surakka , I , Gupta , R , Buchwald , J , Raevuori , A , Ripatti , S , Korhonen , T , Jousilahti , P , Madden , P A F , Kaprio , J & Loukola , A 2019 , ' Genome-wide association study in Finnish twins highlights the connection between nicotine addiction and neurotrophin signaling pathway ' , Addiction Biology , vol. 24 , no. 3 , pp. 549-561 . https://doi.org/10.1111/adb.12618

Title: Genome-wide association study in Finnish twins highlights the connection between nicotine addiction and neurotrophin signaling pathway
Author: Hällfors, Jenni; Palviainen, Teemu; Surakka, Ida; Gupta, Richa; Buchwald, Jadwiga; Raevuori, Anu; Ripatti, Samuli; Korhonen, Tellervo; Jousilahti, Pekka; Madden, Pamela A. F.; Kaprio, Jaakko; Loukola, Anu
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Department of Public Health
University of Helsinki, Centre of Excellence in Complex Disease Genetics
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2019-05
Language: eng
Number of pages: 13
Belongs to series: Addiction Biology
ISSN: 1355-6215
URI: http://hdl.handle.net/10138/301645
Abstract: The heritability of nicotine dependence based on family studies is substantial. Nevertheless, knowledge of the underlying genetic architecture remains meager. Our aim was to identify novel genetic variants responsible for interindividual differences in smoking behavior. We performed a genome-wide association study on 1715 ever smokers ascertained from the population-based Finnish Twin Cohort enriched for heavy smoking. Data imputation used the 1000 Genomes Phase I reference panel together with a whole genome sequence-based Finnish reference panel. We analyzed three measures of nicotine addiction-smoking quantity, nicotine dependence and nicotine withdrawal. We annotated all genome-wide significant SNPs for their functional potential. First, we detected genome-wide significant association on 16p12 with smoking quantity (P = 8.5 x 10(-9)), near CLEC19A. The lead-SNP stands 22 kb from a binding site for NF-kappa B transcription factors, which play a role in the neurotrophin signaling pathway. However, the signal was not replicated in an independent Finnish population-based sample, FINRISK (n = 6763). Second, nicotine withdrawal showed association on 2q21 in an intron of TMEM163 (P = 2.1 x 10(-9)), and on 11p15 (P = 6.6 x 10(-8)) in an intron of AP2A2, and P = 4.2 x 10(-7) for a missense variant in MUC6, both involved in the neurotrophin signaling pathway). Third, association was detected on 3p22.3 for maximum number of cigarettes smoked per day (P = 3.1 x 10(-8)) near STAC. Associating CLEC19A and TMEM163 SNPs were annotated to influence gene expression or methylation. The neurotrophin signaling pathway has previously been associated with smoking behavior. Our findings further support the role in nicotine addiction.
Subject: Finnish population-based imputation reference panel
genome-wide association analysis
neurotrophin signaling pathway
nicotine addiction
nicotine withdrawal
smoking behavior
smoking quantity
NF-KAPPA-B
MIXED-MODEL
DEPENDENCE
EFFICIENT
RECEPTORS
VARIANTS
CLATHRIN
LINKAGE
CLUSTER
LOCUS
1182 Biochemistry, cell and molecular biology
3142 Public health care science, environmental and occupational health
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