Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.
Liu M., Jiang Y., Wedow R., Li Y., Brazel DM., Chen F., Datta G., Davila-Velderrain J., McGuire D., Tian C., Zhan X., 23andMe Research Team None., HUNT All-In Psychiatry None., Choquet H., Docherty AR., Faul JD., Foerster JR., Fritsche LG., Gabrielsen ME., Gordon SD., Haessler J., Hottenga J-J., Huang H., Jang S-K., Jansen PR., Ling Y., Mägi R., Matoba N., McMahon G., Mulas A., Orrù V., Palviainen T., Pandit A., Reginsson GW., Skogholt AH., Smith JA., Taylor AE., Turman C., Willemsen G., Young H., Young KA., Zajac GJM., Zhao W., Zhou W., Bjornsdottir G., Boardman JD., Boehnke M., Boomsma DI., Chen C., Cucca F., Davies GE., Eaton CB., Ehringer MA., Esko T., Fiorillo E., Gillespie NA., Gudbjartsson DF., Haller T., Harris KM., Heath AC., Hewitt JK., Hickie IB., Hokanson JE., Hopfer CJ., Hunter DJ., Iacono WG., Johnson EO., Kamatani Y., Kardia SLR., Keller MC., Kellis M., Kooperberg C., Kraft P., Krauter KS., Laakso M., Lind PA., Loukola A., Lutz SM., Madden PAF., Martin NG., McGue M., McQueen MB., Medland SE., Metspalu A., Mohlke KL., Nielsen JB., Okada Y., Peters U., Polderman TJC., Posthuma D., Reiner AP., Rice JP., Rimm E., Rose RJ., Runarsdottir V., Stallings MC., Stančáková A., Stefansson H., Thai KK., Tindle HA., Tyrfingsson T., Wall TL., Weir DR., Weisner C., Whitfield JB., Winsvold BS., Yin J., Zuccolo L., Bierut LJ., Hveem K., Lee JJ., Munafò MR., Saccone NL., Willer CJ., Cornelis MC., David SP., Hinds DA., Jorgenson E., Kaprio J., Stitzel JA., Stefansson K., Thorgeirsson TE., Abecasis G., Liu DJ., Vrieze S.
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.