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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

Research output: Contribution to journalLetter

  • the 23 and Me Research Team
Original languageEnglish
Pages (from-to)237-244
Number of pages13
JournalNature Genetics
Volume51
Issue number2
Early online date14 Jan 2019
DOIs
DateAccepted/In press - 6 Nov 2018
DateE-pub ahead of print - 14 Jan 2019
DatePublished (current) - 1 Feb 2019

Abstract

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . 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.

    Research areas

  • genome-wide association studies, psychiatric disorders, psychology, public health

    Structured keywords

  • Brain and Behaviour
  • Tobacco and Alcohol

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Springer Nature at https://www.nature.com/articles/s41588-018-0307-5#article-info. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 378 KB, PDF document

  • Supplementary information PDF

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Springer Nature at https://www.nature.com/articles/s41588-018-0307-5#article-info. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 12 KB, PDF document

  • Supplementary information 2 EPS

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Springer Nature at https://www.nature.com/articles/s41588-018-0307-5#article-info. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 10 MB, application/postscript

  • Supplementary information 3 EPS

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Springer Nature at https://www.nature.com/articles/s41588-018-0307-5#article-info. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 9 KB, application/postscript

  • Supplementary information 4 EPS

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Springer Nature at https://www.nature.com/articles/s41588-018-0307-5#article-info. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 10 MB, application/postscript

  • Supplementary information 4A EPS

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Springer Nature at https://www.nature.com/articles/s41588-018-0307-5#article-info. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 10 MB, application/postscript

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