Sandra Sanchez-Roige1, Nancy J Cox2, Eric O Johnson3, Dana B Hancock4, Lea K Davis5. 1. Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA; Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: sanchezroige@ucsd.edu. 2. Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. 3. GenOmics, Bioinformatics, and Translational Research Center, RTI International, Research Triangle Park, NC 27709, USA; Fellow Program, RTI International, Research Triangle Park, NC 27709, USA. 4. GenOmics, Bioinformatics, and Translational Research Center, RTI International, Research Triangle Park, NC 27709, USA. 5. Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Abstract
PURPOSE: To investigate the role of consumption phenotypes as genetic proxies for alcohol misuse and nicotine dependence. METHODS: We leveraged GWAS data from well-powered studies of consumption, alcohol misuse, and nicotine dependence phenotypes measured in individuals of European ancestry from the UK Biobank (UKB) and other population-based cohorts (largest total N = 263,954), and performed genetic correlations within a medical-center cohort, BioVU (N = 66,915). For alcohol, we used quantitative measures of consumption and misuse via AUDIT from UKB. For smoking, we used cigarettes per day from UKB and non-UKB cohorts comprising the GSCAN consortium, and nicotine dependence via ICD codes from UKB and Fagerström Test for Nicotine Dependence from non-UKB cohorts. RESULTS: In a large phenome-wide association study, we show that smoking consumption and dependence phenotypes show similar strongly negatively associations with a plethora of diseases, whereas alcohol consumption shows patterns of genetic association that diverge from those of alcohol misuse. CONCLUSIONS: Our study suggests that cigarette smoking consumption, which can be easily measured in the general population, may be good a genetic proxy for nicotine dependence, whereas alcohol consumption is not a direct genetic proxy of alcohol misuse.
PURPOSE: To investigate the role of consumption phenotypes as genetic proxies for alcohol misuse and nicotine dependence. METHODS: We leveraged GWAS data from well-powered studies of consumption, alcohol misuse, and nicotine dependence phenotypes measured in individuals of European ancestry from the UK Biobank (UKB) and other population-based cohorts (largest total N = 263,954), and performed genetic correlations within a medical-center cohort, BioVU (N = 66,915). For alcohol, we used quantitative measures of consumption and misuse via AUDIT from UKB. For smoking, we used cigarettes per day from UKB and non-UKB cohorts comprising the GSCAN consortium, and nicotine dependence via ICD codes from UKB and Fagerström Test for Nicotine Dependence from non-UKB cohorts. RESULTS: In a large phenome-wide association study, we show that smoking consumption and dependence phenotypes show similar strongly negatively associations with a plethora of diseases, whereas alcohol consumption shows patterns of genetic association that diverge from those of alcohol misuse. CONCLUSIONS: Our study suggests that cigarette smoking consumption, which can be easily measured in the general population, may be good a genetic proxy for nicotine dependence, whereas alcohol consumption is not a direct genetic proxy of alcohol misuse.
Authors: Kyoko Watanabe; Sven Stringer; Oleksandr Frei; Maša Umićević Mirkov; Christiaan de Leeuw; Tinca J C Polderman; Sophie van der Sluis; Ole A Andreassen; Benjamin M Neale; Danielle Posthuma Journal: Nat Genet Date: 2019-08-19 Impact factor: 38.330
Authors: Hang Zhou; Julia M Sealock; Sandra Sanchez-Roige; Toni-Kim Clarke; Daniel F Levey; Zhongshan Cheng; Boyang Li; Renato Polimanti; Rachel L Kember; Rachel Vickers Smith; Johan H Thygesen; Marsha Y Morgan; Stephen R Atkinson; Mark R Thursz; Mette Nyegaard; Manuel Mattheisen; Anders D Børglum; Emma C Johnson; Amy C Justice; Abraham A Palmer; Andrew McQuillin; Lea K Davis; Howard J Edenberg; Arpana Agrawal; Henry R Kranzler; Joel Gelernter Journal: Nat Neurosci Date: 2020-05-25 Impact factor: 24.884
Authors: Henry R Kranzler; Hang Zhou; Rachel L Kember; Rachel Vickers Smith; Amy C Justice; Scott Damrauer; Philip S Tsao; Derek Klarin; Aris Baras; Jeffrey Reid; John Overton; Daniel J Rader; Zhongshan Cheng; Janet P Tate; William C Becker; John Concato; Ke Xu; Renato Polimanti; Hongyu Zhao; Joel Gelernter Journal: Nat Commun Date: 2019-04-02 Impact factor: 14.919
Authors: Jessica Dennis; Julia Sealock; Rebecca T Levinson; Eric Farber-Eger; Jacob Franco; Sarah Fong; Peter Straub; Donald Hucks; Wen-Liang Song; MacRae F Linton; Pierre Fontanillas; Sarah L Elson; Douglas Ruderfer; Abdel Abdellaoui; Sandra Sanchez-Roige; Abraham A Palmer; Dorret I Boomsma; Nancy J Cox; Guanhua Chen; Jonathan D Mosley; Quinn S Wells; Lea K Davis Journal: Mol Psychiatry Date: 2019-12-03 Impact factor: 13.437
Authors: Raymond K Walters; Renato Polimanti; Emma C Johnson; Jeanette N McClintick; Mark J Adams; Amy E Adkins; Fazil Aliev; Silviu-Alin Bacanu; Anthony Batzler; Sarah Bertelsen; Joanna M Biernacka; Tim B Bigdeli; Li-Shiun Chen; Toni-Kim Clarke; Yi-Ling Chou; Franziska Degenhardt; Anna R Docherty; Alexis C Edwards; Pierre Fontanillas; Jerome C Foo; Louis Fox; Josef Frank; Ina Giegling; Scott Gordon; Laura M Hack; Annette M Hartmann; Sarah M Hartz; Stefanie Heilmann-Heimbach; Stefan Herms; Colin Hodgkinson; Per Hoffmann; Jouke Jan Hottenga; Martin A Kennedy; Mervi Alanne-Kinnunen; Bettina Konte; Jari Lahti; Marius Lahti-Pulkkinen; Dongbing Lai; Lannie Ligthart; Anu Loukola; Brion S Maher; Hamdi Mbarek; Andrew M McIntosh; Matthew B McQueen; Jacquelyn L Meyers; Yuri Milaneschi; Teemu Palviainen; John F Pearson; Roseann E Peterson; Samuli Ripatti; Euijung Ryu; Nancy L Saccone; Jessica E Salvatore; Sandra Sanchez-Roige; Melanie Schwandt; Richard Sherva; Fabian Streit; Jana Strohmaier; Nathaniel Thomas; Jen-Chyong Wang; Bradley T Webb; Robbee Wedow; Leah Wetherill; Amanda G Wills; Jason D Boardman; Danfeng Chen; Doo-Sup Choi; William E Copeland; Robert C Culverhouse; Norbert Dahmen; Louisa Degenhardt; Benjamin W Domingue; Sarah L Elson; Mark A Frye; Wolfgang Gäbel; Caroline Hayward; Marcus Ising; Margaret Keyes; Falk Kiefer; John Kramer; Samuel Kuperman; Susanne Lucae; Michael T Lynskey; Wolfgang Maier; Karl Mann; Satu Männistö; Bertram Müller-Myhsok; Alison D Murray; John I Nurnberger; Aarno Palotie; Ulrich Preuss; Katri Räikkönen; Maureen D Reynolds; Monika Ridinger; Norbert Scherbaum; Marc A Schuckit; Michael Soyka; Jens Treutlein; Stephanie Witt; Norbert Wodarz; Peter Zill; Daniel E Adkins; Joseph M Boden; Dorret I Boomsma; Laura J Bierut; Sandra A Brown; Kathleen K Bucholz; Sven Cichon; E Jane Costello; Harriet de Wit; Nancy Diazgranados; Danielle M Dick; Johan G Eriksson; Lindsay A Farrer; Tatiana M Foroud; Nathan A Gillespie; Alison M Goate; David Goldman; Richard A Grucza; Dana B Hancock; Kathleen Mullan Harris; Andrew C Heath; Victor Hesselbrock; John K Hewitt; Christian J Hopfer; John Horwood; William Iacono; Eric O Johnson; Jaakko A Kaprio; Victor M Karpyak; Kenneth S Kendler; Henry R Kranzler; Kenneth Krauter; Paul Lichtenstein; Penelope A Lind; Matt McGue; James MacKillop; Pamela A F Madden; Hermine H Maes; Patrik Magnusson; Nicholas G Martin; Sarah E Medland; Grant W Montgomery; Elliot C Nelson; Markus M Nöthen; Abraham A Palmer; Nancy L Pedersen; Brenda W J H Penninx; Bernice Porjesz; John P Rice; Marcella Rietschel; Brien P Riley; Richard Rose; Dan Rujescu; Pei-Hong Shen; Judy Silberg; Michael C Stallings; Ralph E Tarter; Michael M Vanyukov; Scott Vrieze; Tamara L Wall; John B Whitfield; Hongyu Zhao; Benjamin M Neale; Joel Gelernter; Howard J Edenberg; Arpana Agrawal Journal: Nat Neurosci Date: 2018-11-26 Impact factor: 24.884
Authors: Mengzhen Liu; Yu Jiang; Robbee Wedow; Yue Li; David M Brazel; Fang Chen; Gargi Datta; Jose Davila-Velderrain; Daniel McGuire; Chao Tian; Xiaowei Zhan; 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 Journal: Nat Genet Date: 2019-01-14 Impact factor: 38.330
Authors: Ke Xu; Boyang Li; Kathleen A McGinnis; Rachel Vickers-Smith; Cecilia Dao; Ning Sun; Rachel L Kember; Hang Zhou; William C Becker; Joel Gelernter; Henry R Kranzler; Hongyu Zhao; Amy C Justice Journal: Nat Commun Date: 2020-10-20 Impact factor: 14.919
Authors: Bryan C Quach; Michael J Bray; Nathan C Gaddis; Mengzhen Liu; Teemu Palviainen; Camelia C Minica; Stephanie Zellers; Richard Sherva; Fazil Aliev; Michael Nothnagel; Kendra A Young; Jesse A Marks; Hannah Young; Megan U Carnes; Yuelong Guo; Alex Waldrop; Nancy Y A Sey; Maria T Landi; Daniel W McNeil; Dmitriy Drichel; Lindsay A Farrer; Christina A Markunas; Jacqueline M Vink; Jouke-Jan Hottenga; William G Iacono; Henry R Kranzler; Nancy L Saccone; Michael C Neale; Pamela Madden; Marcella Rietschel; Mary L Marazita; Matthew McGue; Hyejung Won; Georg Winterer; Richard Grucza; Danielle M Dick; Joel Gelernter; Neil E Caporaso; Timothy B Baker; Dorret I Boomsma; Jaakko Kaprio; John E Hokanson; Scott Vrieze; Laura J Bierut; Eric O Johnson; Dana B Hancock Journal: Nat Commun Date: 2020-11-03 Impact factor: 17.694
Authors: Ryan Bogdan; Arpana Agrawal; Alexander S Hatoum; Emma C Johnson; Sarah M C Colbert; Renato Polimanti; Hang Zhou; Raymond K Walters; Joel Gelernter; Howard J Edenberg Journal: Neuropsychopharmacology Date: 2021-11-08 Impact factor: 8.294
Authors: Vanessa Troiani; Richard C Crist; Glenn A Doyle; Thomas N Ferraro; Donielle Beiler; Stephanie Ranck; Kortney McBryan; Margaret A Jarvis; Jordan S Barbour; John J Han; Ryan J Ness; Wade H Berrettini; Janet D Robishaw Journal: BMC Med Genomics Date: 2021-10-26 Impact factor: 3.063