Genome-wide association meta-analysis of nicotine metabolism and cigarette consumption measures in smokers of European descent.

Molecular Psychiatry
Jadwiga BuchwaldRachel F Tyndale

Abstract

Smoking behaviors, including amount smoked, smoking cessation, and tobacco-related diseases, are altered by the rate of nicotine clearance. Nicotine clearance can be estimated using the nicotine metabolite ratio (NMR) (ratio of 3'hydroxycotinine/cotinine), but only in current smokers. Advancing the genomics of this highly heritable biomarker of CYP2A6, the main metabolic enzyme for nicotine, will also enable investigation of never and former smokers. We performed the largest genome-wide association study (GWAS) to date of the NMR in European ancestry current smokers (n = 5185), found 1255 genome-wide significant variants, and replicated the chromosome 19 locus. Fine-mapping of chromosome 19 revealed 13 putatively causal variants, with nine of these being highly putatively causal and mapping to CYP2A6, MAP3K10, ADCK4, and CYP2B6. We also identified a putatively causal variant on chromosome 4 mapping to TMPRSS11E and demonstrated an association between TMPRSS11E variation and a UGT2B17 activity phenotype. Together the 14 putatively causal SNPs explained ~38% of NMR variation, a substantial increase from the ~20 to 30% previously explained. Our additional GWASs of nicotine intake biomarkers showed that cotinine and smoking intensi...Continue Reading

References

Jan 1, 1997·Journal of the American Academy of Child and Adolescent Psychiatry·S MilbergerJ Jones
Feb 21, 2002·Journal of Epidemiology and Community Health·E VartiainenP Puska
Apr 12, 2002·American Journal of Epidemiology·Harvey CheckowayPhillip D Swanson
Jul 2, 2004·Clinical Pharmacology and Therapeutics·Delia DempseyNeal L Benowitz
Mar 27, 2007·Bioinformatics·Yurii S AulchenkoCornelia M van Duijn
Jun 19, 2008·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Marc E MooneyDorothy K Hatsukami
Nov 21, 2008·Pharmacogenomics·Ana RossiniLuis Felipe Ribeiro Pinto
Feb 3, 2009·Handbook of Experimental Pharmacology·Neal L BenowitzPeyton Jacob
Apr 14, 2009·Human Molecular Genetics·Minori KogaTadao Arinami
Oct 23, 2009·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·K MuraiT Kamataki
Apr 27, 2010·Nature Genetics·Jason Z LiuJonathan Marchini
Jun 1, 2010·BMC Bioinformatics·Reedik Mägi, Andrew P Morris
Jun 18, 2010·The New England Journal of Medicine·Neal L Benowitz
Jul 17, 2010·Bioinformatics·Randall J PruimCristen J Willer
Dec 21, 2010·American Journal of Human Genetics·Jian YangPeter M Visscher
Mar 9, 2011·IEEE Transactions on Visualization and Computer Graphics·Leland Wilkinson
May 17, 2011·The American Journal of Psychiatry·Michele L PergadiaPamela A F Madden
Jul 13, 2011·Journal of the National Cancer Institute·Catherine A WassenaarRachel F Tyndale
Jan 10, 2012·Pharmacogenetics and Genomics·Gang ChenPhilip Lazarus
Jun 19, 2012·Nature Genetics·Xiang Zhou, Matthew Stephens
Nov 20, 2012·Annual Review of Clinical Psychology·Sherry A McKee, Andrea H Weinberger
Feb 2, 2013·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Andy Z X ZhuRachel F Tyndale
May 16, 2013·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Gideon St HelenNeal L Benowitz
Jul 9, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ikuo YamamiyaMasato Chiba
Jul 12, 2014·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Meghan J ChenowethRachel F Tyndale
Feb 3, 2015·Nature Genetics·Brendan K Bulik-SullivanBenjamin M Neale
May 28, 2015·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Julie-Anne TannerRachel F Tyndale
Sep 26, 2015·PLoS Genetics·Anu LoukolaJaakko Kaprio
Feb 3, 2016·Scientific Reports·Jennifer J WareMarcus R Munafò
Apr 25, 2016·Drug and Alcohol Dependence·Noah R GubnerMaciej L Goniewicz
Apr 27, 2016·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·James W BaurleyAndrew W Bergen
Aug 5, 2016·Cancer Research·Yesha M PatelLoïc Le Marchand
Oct 8, 2016·Trends in Pharmacological Sciences·Meghan J Chenoweth, Rachel F Tyndale
Dec 2, 2017·Journal of Personalized Medicine·Julie-Anne Tanner, Rachel F Tyndale

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Citations

Dec 17, 2020·Expert Opinion on Drug Metabolism & Toxicology·Yadira X Perez-Paramo, Philip Lazarus
Apr 6, 2021·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Rafael MaldonadoElena Martín-García
May 2, 2021·The Journal of Biological Chemistry·Sharon E Murphy
Apr 7, 2021·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Kevin ButlerBernard Le Foll
Jul 25, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Joanna M BiernackaVictor M Karpyak
Apr 25, 2021·Genes, Brain, and Behavior·Rohan H C PalmerRobert W Williams
Jul 28, 2021·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Andrew W BergenJames W Baurley
Aug 4, 2021·Twin Research and Human Genetics : the Official Journal of the International Society for Twin Studies·Adrian I CamposMiguel E Rentería

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