| Title: | Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits |
| Journal: | Nature Communications |
| Published: | 3 Nov 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33144568/ |
| DOI: | https://doi.org/10.1038/s41467-020-19265-z |
| URL: | https://www.nature.com/articles/s41467-020-19265-z.pdf |
| Citations: | 96 (34 in last 2 years) as of 8 Aug 2024 |
Publication 4826
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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 Fagerström 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 (rg = 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.</p>
46 Authors
- Bryan C. Quach
- Michael J. Bray
- Nathan C. Gaddis
- Mengzhen Liu
- Teemu Palviainen
- Camelia C. Minica
- Stephanie Zellers
- Richard Sherva
- Fazil Aliev
- Michael Nothnagel
- Kendra A. Young
- Jesse A. Marks
- Hannah Young
- Megan U. Carnes
- Yuelong Guo
- Alex Waldrop
- Nancy Y. A. Sey
- Maria T. Landi
- Daniel W. McNeil
- Dmitriy Drichel
- Lindsay A. Farrer
- Christina A. Markunas
- Jacqueline M. Vink
- Jouke-Jan Hottenga
- William G. Iacono
- Henry R. Kranzler
- Nancy L. Saccone
- Michael C. Neale
- Pamela Madden
- Marcella Rietschel
- Mary L. Marazita
- Matthew McGue
- Hyejung Won
- Georg Winterer
- Richard Grucza
- Danielle M. Dick
- Joel Gelernter
- Neil E. Caporaso
- Timothy B. Baker
- Dorret I. Boomsma
- Jaakko Kaprio
- John E. Hokanson
- Scott Vrieze
- Laura J. Bierut
- Eric O. Johnson
- Dana B. Hancock
Enabling scientific discoveries that improve human health