title: Smoking and caffeine consumption: a genetic analysis of their association.
abstract: Smoking and caffeine consumption show a strong positive correlation, but the mechanism underlying this association is unclear. Explanations include shared genetic/environmental factors or causal effects. This study employed three methods to investigate the association between smoking and caffeine. First, bivariate genetic models were applied to data of 10 368 twins from the Netherlands Twin Register in order to estimate genetic and environmental correlations between smoking and caffeine use. Second, from the summary statistics of meta-analyses of genome-wide association studies on smoking and caffeine, the genetic correlation was calculated by LD-score regression. Third, causal effects were tested using Mendelian randomization analysis in 6605 Netherlands Twin Register participants and 5714 women from the Avon Longitudinal Study of Parents and Children. Through twin modelling, a genetic correlation of r0.47 and an environmental correlation of r0.30 were estimated between current smoking (yes/no) and coffee use (high/low). Between current smoking and total caffeine use, this was r0.44 and r0.00, respectively. LD-score regression also indicated sizeable genetic correlations between smoking and coffee use (r0.44 between smoking heaviness and cups of coffee per day, r0.28 between smoking initiation and coffee use and r0.25 between smoking persistence and coffee use). Consistent with the relatively high genetic correlations and lower environmental correlations, Mendelian randomization provided no evidence for causal effects of smoking on caffeine or vice versa. Genetic factors thus explain most of the association between smoking and caffeine consumption. These findings suggest that quitting smoking may be more difficult for heavy caffeine consumers, given their genetic susceptibility.
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.|EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jorien L
authors.initials: JL
authors.lastname: Treur
authors.affiliation: UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, UK.|MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Taylor
authors.affiliation: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Ware
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Michel G
authors.initials: MG
authors.lastname: Nivard
authors.affiliation: Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
authors.affiliation: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: George
authors.initials: G
authors.lastname: McMahon
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.|EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jouke-Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.|EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Bart M L
authors.initials: BML
authors.lastname: Baselmans
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.|EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.affiliation: UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, UK.|MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Munafò
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.|EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Vink
mesh_terms: D000328:Adult; D002110:Caffeine / Q000008:administration & dosage*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D005260:Female; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology* / Q000235:genetics; D011795:Surveys and Questionnaires; D014427:Twins / Q000235:genetics / Q000706:statistics & numerical data
chemical_list: D000697:Central Nervous System Stimulants; D002110:Caffeine
keywords: ALSPAC; LD-score regression; Mendelian randomization; caffeine; smoking; twin modelling