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

the 23 and Me Research Team

doi:10.1038/s41588-018-0307-5

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

the 23 and Me Research Team

Research output: Contribution to journal › Letter (Academic Journal) › peer-review

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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.

Original language	English
Pages (from-to)	237-244
Number of pages	8
Journal	Nature Genetics
Volume	51
Issue number	2
Early online date	14 Jan 2019
DOIs	https://doi.org/10.1038/s41588-018-0307-5
Publication status	Published - 1 Feb 2019

Research Groups and Themes

Brain and Behaviour
Tobacco and Alcohol
Physical and Mental Health

Keywords

genome-wide association studies
psychiatric disorders
psychology
public health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41588-018-0307-5

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Supplementary information 2 EPS
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, 10.8 MB
Supplementary information 3 EPS
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, 9.91 KB
Supplementary information 4 EPS
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, 10.4 MB
Supplementary information 4A EPS
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, 10.4 MB

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Cite this

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title = "Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use",

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. ",

keywords = "genome-wide association studies, psychiatric disorders, psychology, public health",

author = "Mengzhen Liu and Yu Jiang and Robbee Wedow and Yue Li and Brazel, {David M} and Fang Chen and Gargi Datta and Jose Davila-Velderrain and Daniel McGuire and Chao Tian and Xiaowei Zhan and H{\'e}l{\`e}ne Choquet and Docherty, {Anna R} and Faul, {Jessica D} and Foerster, {Johanna R} and Fritsche, {Lars G} and Gabrielsen, {Maiken Elvestad} and Gordon, {Scott D} and Jeffrey Haessler and Jouke-Jan Hottenga and Hongyan Huang and Seon-Kyeong Jang and Jansen, {Philip R} and Yueh Ling and Reedik M{\"a}gi and Nana Matoba and George McMahon and Antonella Mulas and Valeria Orr{\`u} and Teemu Palviainen and Anita Pandit and Reginsson, {Gunnar W} and Skogholt, {Anne Heidi} and Smith, {Jennifer A} and Taylor, {Amy E} and Constance Turman and Gonneke Willemsen and Hannah Young and Young, {Kendra A} and Zajac, {Gregory J M} and Wei Zhao and Wei Zhou and Gyda Bjornsdottir and Boardman, {Jason D} and Davies, {Gareth E} and Medland, {Sarah E} and Weir, {David R} and Luisa Zuccolo and Munaf{\`o}, {Marcus R} and Cornelis, {Marilyn C} and {the 23 and Me Research Team}",

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AU - Liu, Mengzhen

AU - Jiang, Yu

AU - Wedow, Robbee

AU - Li, Yue

AU - Brazel, David M

AU - Chen, Fang

AU - Datta, Gargi

AU - Davila-Velderrain, Jose

AU - McGuire, Daniel

AU - Tian, Chao

AU - Zhan, Xiaowei

AU - Choquet, Hélène

AU - Docherty, Anna R

AU - Faul, Jessica D

AU - Foerster, Johanna R

AU - Fritsche, Lars G

AU - Gabrielsen, Maiken Elvestad

AU - Gordon, Scott D

AU - Haessler, Jeffrey

AU - Hottenga, Jouke-Jan

AU - Huang, Hongyan

AU - Jang, Seon-Kyeong

AU - Jansen, Philip R

AU - Ling, Yueh

AU - Mägi, Reedik

AU - Matoba, Nana

AU - McMahon, George

AU - Mulas, Antonella

AU - Orrù, Valeria

AU - Palviainen, Teemu

AU - Pandit, Anita

AU - Reginsson, Gunnar W

AU - Skogholt, Anne Heidi

AU - Smith, Jennifer A

AU - Taylor, Amy E

AU - Turman, Constance

AU - Willemsen, Gonneke

AU - Young, Hannah

AU - Young, Kendra A

AU - Zajac, Gregory J M

AU - Zhao, Wei

AU - Zhou, Wei

AU - Bjornsdottir, Gyda

AU - Boardman, Jason D

AU - Davies, Gareth E

AU - Medland, Sarah E

AU - Weir, David R

AU - Zuccolo, Luisa

AU - Munafò, Marcus R

AU - Cornelis, Marilyn C

AU - the 23 and Me Research Team

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

KW - genome-wide association studies

KW - psychiatric disorders

KW - psychology

KW - public health

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U2 - 10.1038/s41588-018-0307-5

DO - 10.1038/s41588-018-0307-5

M3 - Letter (Academic Journal)

C2 - 30643251

SN - 1061-4036

VL - 51

SP - 237

EP - 244

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

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

Abstract

Research Groups and Themes

Keywords

UN SDGs

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Professor Marcus R Munafo

Dr Amy E Taylor

Cite this

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

Abstract

Research Groups and Themes

Keywords

UN SDGs

Access to Document

Handle.net

Other files and links

Fingerprint

Profiles

Professor Marcus R Munafo

Dr Amy E Taylor

Cite this