RT Journal Article
SR Electronic
T1 Expanding the Genetic Architecture of Nicotine Dependence and its Shared Genetics with Multiple Traits: Findings from the Nicotine Dependence GenOmics (iNDiGO) Consortium
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.15.898858
DO 10.1101/2020.01.15.898858
A1 Bryan C. Quach
A1 Michael J. Bray
A1 Nathan C. Gaddis
A1 Mengzhen Liu
A1 Teemu Palviainen
A1 Camelia C. Minica
A1 Stephanie Zellers
A1 Richard Sherva
A1 Fazil Aliev
A1 Michael Nothnagel
A1 Kendra A. Young
A1 Jesse A. Marks
A1 Hannah Young
A1 Megan U. Carnes
A1 Yuelong Guo
A1 Alex Waldrop
A1 Nancy Y.A. Sey
A1 Maria T. Landi
A1 Daniel W. McNeil
A1 Dmitriy Drichel
A1 Lindsay A. Farrer
A1 Christina A. Markunas
A1 Jacqueline M. Vink
A1 Jouke-Jan Hottenga
A1 William G. Iacono
A1 Henry R. Kranzler
A1 Nancy L. Saccone
A1 Michael C. Neale
A1 Pamela Madden
A1 Marcella Rietschel
A1 Mary L. Marazita
A1 Matthew McGue
A1 Hyejung Won
A1 Georg Winterer and the German Nicotine Cohort Study
A1 Richard Grucza
A1 Danielle M. Dick
A1 Joel Gelernter
A1 Neil E. Caporaso
A1 Timothy B. Baker
A1 Dorret I. Boomsma
A1 Jaakko Kaprio
A1 John E. Hokanson
A1 Scott Vrieze
A1 Laura J. Bierut
A1 Eric O. Johnson
A1 Dana B. Hancock
YR 2020
UL http://biorxiv.org/content/early/2020/07/09/2020.01.15.898858.abstract
AB Cigarette smoking is the leading cause of preventable morbidity and mortality. Knowledge is evolving on genetics underlying initiation, regular smoking, nicotine dependence (ND), and cessation. We performed a genome-wide association study using the Fagerström Test for ND (FTND) in 58,000 smokers of European or African ancestry. Five genome-wide significant loci, including two novel loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416) were identified, and loci reported for other smoking traits were extended to ND. Using the heaviness of smoking index (HSI) in the UK Biobank (N=33,791), rs2714700 was consistently associated, but rs1862416 was not associated, likely reflecting ND features not captured by the HSI. Both variants were cis-eQTLs (rs2714700 for MAGI2-AS3 in hippocampus, rs1862416 for TENM2 in lung), and expression of genes spanning ND-associated variants was enriched in cerebellum. SNP-based heritability of ND was 8.6%, and ND was genetically correlated with 17 other smoking traits (rg=0.40–0.95) and co-morbidities. Our results emphasize the FTND as a composite phenotype that expands genetic knowledge of smoking, including loci specific to ND.Competing Interest StatementL.J.B. and the spouse of N.L.S. are listed as inventors on U.S. Patent 8,080,371, 'Markers for Addiction' covering the use of certain SNPs in determining the diagnosis, prognosis, and treatment of addiction. Y.G. is an employee of GeneCentric Therapeutics. Although unrelated to this research, H.R.K. is an advisory board member for Dicerna and a member of the American Society of Clinical Psychopharmacology's Alcohol Clinical Trials Initiative, which was supported in the last 3 years by AbbVie, Alkermes, Ethypharm, Indivior, Lilly, Lundbeck, Otsuka, Pfizer, Arbor and Amygdala Neurosciences. H.R.K. and J.G. are named as inventors on PCT patent application #15/878,640 entitled: "Genotype-guided dosing of opioid agonists," filed January 24, 2018. J.K. consulted for Pfizer in 2012-2015 on ND. All other authors declare no conflict of interest.