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Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Mengzhen Liu | Yu Jiang | Robbee Wedow | Yue Li | David M Brazel | Fang Chen | Gargi Datta | Jose Davila-Velderrain | Daniel McGuire | Chao Tian | Xiaowei Zhan | 23andMe Research Team | HUNT All-In Psychiatry | Hélène Choquet | Anna R Docherty | Jessica D Faul | Johanna R Foerster | Lars G Fritsche | Maiken Elvestad Gabrielsen | Scott D Gordon | Jeffrey Haessler | Jouke-Jan Hottenga | Hongyan Huang | Seon-Kyeong Jang | Philip R Jansen | Yueh Ling | Reedik Mägi | Nana Matoba | George McMahon | Antonella Mulas | Valeria Orrù | Teemu Palviainen | Anita Pandit | Gunnar W Reginsson | Anne Heidi Skogholt | Jennifer A Smith | Amy E Taylor | Constance Turman | Gonneke Willemsen | Hannah Young | Kendra A Young | Gregory J M Zajac | Wei Zhao | Wei Zhou | Gyda Bjornsdottir | Jason D Boardman | Michael Boehnke | Dorret I Boomsma | Chu Chen | Francesco Cucca | Gareth E Davies | Charles B Eaton | Marissa A Ehringer | Tõnu Esko | Edoardo Fiorillo | Nathan A Gillespie | Daniel F Gudbjartsson | Toomas Haller | Kathleen Mullan Harris | Andrew C Heath | John K Hewitt | Ian B Hickie | John E Hokanson | Christian J Hopfer | David J Hunter | William G Iacono | Eric O Johnson | Yoichiro Kamatani | Sharon L R Kardia | Matthew C Keller | Manolis Kellis | Charles Kooperberg | Peter Kraft | Kenneth S Krauter | Markku Laakso | Penelope A Lind | Anu Loukola | Sharon M Lutz | Pamela A F Madden | Nicholas G Martin | Matt McGue | Matthew B McQueen | Sarah E Medland | Andres Metspalu | Karen L Mohlke | Jonas B Nielsen | Yukinori Okada | Ulrike Peters | Tinca J C Polderman | Danielle Posthuma | Alexander P Reiner | John P Rice | Eric Rimm | Richard J Rose | Valgerdur Runarsdottir | Michael C Stallings | Alena Stančáková | Hreinn Stefansson | Khanh K Thai | Hilary A Tindle | Thorarinn Tyrfingsson | Tamara L Wall | David R Weir | Constance Weisner | John B Whitfield | Bendik Slagsvold Winsvold | Jie Yin | Luisa Zuccolo | Laura J Bierut | Kristian Hveem | James J Lee | Marcus R Munafò | Nancy L Saccone | Cristen J Willer | Marilyn C Cornelis | Sean P David | David A Hinds | Eric Jorgenson | Jaakko Kaprio | Jerry A Stitzel | Kari Stefansson | Thorgeir E Thorgeirsson | Gonçalo Abecasis | Dajiang J Liu | Scott Vrieze
Nature genetics | 2019

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures.

Pubmed ID: 30643251 RIS Download

Research resources used in this publication

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Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK093757
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL089897
  • Agency: NICHD NIH HHS, United States
    Id: P01 HD031921
  • Agency: NIA NIH HHS, United States
    Id: U01 AG009740
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM126479
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12013/1
  • Agency: NHGRI NIH HHS, United States
    Id: T32 HG000040
  • Agency: NICHD NIH HHS, United States
    Id: R03 HD097630
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA042755
  • Agency: NICHD NIH HHS, United States
    Id: P2C HD066613
  • Agency: NIMH NIH HHS, United States
    Id: K01 MH109765
  • Agency: NHLBI NIH HHS, United States
    Id: K01 HL125858
  • Agency: Medical Research Council, United Kingdom
    Id: G0902144
  • Agency: NIDCD NIH HHS, United States
    Id: R03 DC013373
  • Agency: NIDA NIH HHS, United States
    Id: R21 DA040177
  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL089897
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK072193
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL119443
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK062370
  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL089856
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA034076
  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG008983
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA036583
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK116738
  • Agency: NIDDK NIH HHS, United States
    Id: U01 DK062370
  • Agency: NIAAA NIH HHS, United States
    Id: R21 AA021223
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA037904
  • Agency: NIDA NIH HHS, United States
    Id: U01 DA046413
  • Agency: NIAAA NIH HHS, United States
    Id: R01 AA023974
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK020572
  • Agency: NIH HHS, United States
    Id: S10 OD020069
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_00011/7
  • Agency: NIDDK NIH HHS, United States
    Id: T32 DK091317
  • Agency: Medical Research Council, United Kingdom
    Id: MR/K023195/1
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH123619

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This is a list of tools and resources that we have found mentioned in this publication.


PLINK (tool)

RRID:SCR_001757

Open source whole genome association analysis toolset, designed to perform range of basic, large scale analyses in computationally efficient manner. Used for analysis of genotype/phenotype data. Through integration with gPLINK and Haploview, there is some support for subsequent visualization, annotation and storage of results. PLINK 1.9 is improved and second generation of the software.

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LOCUSZOOM (tool)

RRID:SCR_009257

Software application designed to facilitate viewing of local association results together with useful information about a locus, such as the location and orientation of the genes it includes, linkage disequilibrium coefficients and local estimates of recombination rates. It was developed by popular demand, as a result of many questions we have had about How did you make the figures in your talk? or How did you make the figures for your GWAS paper? (entry from Genetic Analysis Software)

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