Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits

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http://hdl.handle.net/10138/330761

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Quach , B C , Bray , M J , Gaddis , N C , Liu , M , Palviainen , T , Minica , C C , Zellers , S , Sherva , R , Aliev , F , Nothnagel , M , Young , K A , Marks , J A , Young , H , Carnes , M U , Guo , Y , Waldrop , A , Sey , N Y A , Landi , M T , McNeil , D W , Drichel , D , Farrer , L A , Markunas , C A , Vink , J M , Hottenga , J-J , Iacono , W G , Kranzler , H R , Saccone , N L , Neale , M C , Madden , P , Rietschel , M , Marazita , M L , McGue , M , Won , H , Winterer , G , Grucza , R , Dick , D M , Gelernter , J , Caporaso , N E , Baker , T B , Boomsma , D I , Kaprio , J , Hokanson , J E , Vrieze , S , Bierut , L J , Johnson , E O & Hancock , D B 2020 , ' Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits ' , Nature Communications , vol. 11 , no. 1 , 5562 . https://doi.org/10.1038/s41467-020-19265-z

Title: Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits
Author: Quach, Bryan C.; Bray, Michael J.; Gaddis, Nathan C.; Liu, Mengzhen; Palviainen, Teemu; Minica, Camelia C.; Zellers, Stephanie; Sherva, Richard; Aliev, Fazil; Nothnagel, Michael; Young, Kendra A.; Marks, Jesse A.; Young, Hannah; Carnes, Megan U.; Guo, Yuelong; Waldrop, Alex; Sey, Nancy Y. A.; Landi, Maria T.; McNeil, Daniel W.; Drichel, Dmitriy; Farrer, Lindsay A.; Markunas, Christina A.; Vink, Jacqueline M.; Hottenga, Jouke-Jan; Iacono, William G.; Kranzler, Henry R.; Saccone, Nancy L.; Neale, Michael C.; Madden, Pamela; Rietschel, Marcella; Marazita, Mary L.; McGue, Matthew; Won, Hyejung; Winterer, Georg; Grucza, Richard; Dick, Danielle M.; Gelernter, Joel; Caporaso, Neil E.; Baker, Timothy B.; Boomsma, Dorret I.; Kaprio, Jaakko; Hokanson, John E.; Vrieze, Scott; Bierut, Laura J.; Johnson, Eric O.; Hancock, Dana B.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2020-11-03
Language: eng
Number of pages: 13
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/330761
Abstract: Cigarette smoking is the leading cause of preventable morbidity and mortality. Genetic variation contributes to initiation, regular smoking, nicotine dependence, and cessation. We present a Fagerstrom Test for Nicotine Dependence (FTND)-based genome-wide association study in 58,000 European or African ancestry smokers. We observe five genome-wide significant loci, including previously unreported loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416), and extend loci reported for other smoking traits to nicotine dependence. Using the heaviness of smoking index from UK Biobank (N=33,791), rs2714700 is consistently associated; rs1862416 is not associated, likely reflecting nicotine dependence features not captured by the heaviness of smoking index. Both variants influence nearby gene expression (rs2714700/MAGI2-AS3 in hippocampus; rs1862416/TENM2 in lung), and expression of genes spanning nicotine dependence-associated variants is enriched in cerebellum. Nicotine dependence (SNP-based heritability = 8.6%) is genetically correlated with 18 other smoking traits (r(g)=0.40-1.09) and co-morbidities. Our results highlight nicotine dependence-specific loci, emphasizing the FTND as a composite phenotype that expands genetic knowledge of smoking. There is strong genetic evidence for cigarette smoking behaviors, yet little is known on nicotine dependence (ND). Here, the authors perform a genome-wide association study on ND in 58,000 smokers, identifying five genome-wide significant loci.
Subject: GENOME-WIDE ASSOCIATION
TOBACCO DEPENDENCE
LUNG-CANCER
FAGERSTROM TEST
WISCONSIN INVENTORY
SMOKING-CESSATION
VARIANTS
EXPRESSION
INSIGHTS
LOCI
1184 Genetics, developmental biology, physiology
3142 Public health care science, environmental and occupational health
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