Jorim J Tielbeek1, Jacqueline M Vink2, Tinca J C Polderman3, Arne Popma4, Danielle Posthuma3, Karin J H Verweij5. 1. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, VU University, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands; Department of Child and Adolescent Psychiatry, VU University Medical Center, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands. 2. Behavioural Science Institute, Radboud University, Montessorilaan 3, 6525 HR Nijmegen, The Netherlands. 3. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, VU University, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands. 4. Department of Child and Adolescent Psychiatry, VU University Medical Center, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands. 5. Behavioural Science Institute, Radboud University, Montessorilaan 3, 6525 HR Nijmegen, The Netherlands; Department of Biological Psychology/Netherlands Twin Register, VU University, van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands; Department of Psychiatry, Amsterdam Medical Center, University of Amsterdam, Meibergdreef 5, 1105 AZ Amsterdam, The Netherlands. Electronic address: karin.verweij@amc.nl.
Abstract
BACKGROUND: There is high comorbidity between antisocial behaviour (ASB) and substance use, and twin studies have shown that part of the covariation is due to overlapping genetic influences. Here we used measured genetic effects to estimate the genetic correlations of ASB with nicotine, alcohol, and cannabis use. METHODS: We meta-analysed data from two genome-wide association studies for ASB and used existing summary statistics from the largest genome-wide association studies into substance use (ever smoking, cigarettes smoked per day, weekly alcohol consumption, and lifetime cannabis use). We performed cross-trait LD-score regression to estimate genetic correlations between ASB and substance use phenotypes explained by all single nucleotide polymorphisms (SNPs). When significant, we tested whether the signs of the regression coefficients of SNPs from the ASB and substance use phenotypes were in the same direction across multiple p-value thresholds and examined enrichment in overlap of the strongest associated SNPs. RESULTS: We found nominally significant genetic correlations of ASB with lifetime cannabis use (rg = 0.69, p=.016) and cigarettes per day (rg = 0.59, p = 0.036) but not with weekly alcohol consumption or ever smoking. Sign-tests revealed consistent directions of effect of SNPs for ASB and cannabis use for all p-value thresholds except the most stringent one, whereas for ASB with cigarettes per day no consistent evidence was found. We found no evidence of enrichment in overlap of the most associated SNPs across these traits. CONCLUSION: Using measured genetic variants, we found preliminary support for a genetic correlation of ASB with lifetime cannabis use and cigarettes per day.
BACKGROUND: There is high comorbidity between antisocial behaviour (ASB) and substance use, and twin studies have shown that part of the covariation is due to overlapping genetic influences. Here we used measured genetic effects to estimate the genetic correlations of ASB with nicotine, alcohol, and cannabis use. METHODS: We meta-analysed data from two genome-wide association studies for ASB and used existing summary statistics from the largest genome-wide association studies into substance use (ever smoking, cigarettes smoked per day, weekly alcohol consumption, and lifetime cannabis use). We performed cross-trait LD-score regression to estimate genetic correlations between ASB and substance use phenotypes explained by all single nucleotide polymorphisms (SNPs). When significant, we tested whether the signs of the regression coefficients of SNPs from the ASB and substance use phenotypes were in the same direction across multiple p-value thresholds and examined enrichment in overlap of the strongest associated SNPs. RESULTS: We found nominally significant genetic correlations of ASB with lifetime cannabis use (rg = 0.69, p=.016) and cigarettes per day (rg = 0.59, p = 0.036) but not with weekly alcohol consumption or ever smoking. Sign-tests revealed consistent directions of effect of SNPs for ASB and cannabis use for all p-value thresholds except the most stringent one, whereas for ASB with cigarettes per day no consistent evidence was found. We found no evidence of enrichment in overlap of the most associated SNPs across these traits. CONCLUSION: Using measured genetic variants, we found preliminary support for a genetic correlation of ASB with lifetime cannabis use and cigarettes per day.
Authors: Stephanie M Zellers; Robin Corley; Eric Thibodeau; Robert Kirkpatrick; Irene Elkins; William G Iacono; Christian Hopfer; John K Hewitt; Matt McGue; Scott Vrieze Journal: Behav Genet Date: 2020-02-08 Impact factor: 2.805
Authors: Camelia C Minică; Karin J H Verweij; Peter J van der Most; Hamdi Mbarek; Manon Bernard; Kristel R van Eijk; Penelope A Lind; Meng Zhen Liu; Dominique F Maciejewski; Teemu Palviainen; Cristina Sánchez-Mora; Richard Sherva; Michelle Taylor; Raymond K Walters; Abdel Abdellaoui; Timothy B Bigdeli; Susan J T Branje; Sandra A Brown; Miguel Casas; Robin P Corley; George Davey-Smith; Gareth E Davies; Erik A Ehli; Lindsay Farrer; Iryna O Fedko; Iris Garcia-Martínez; Scott D Gordon; Catharina A Hartman; Andrew C Heath; Ian B Hickie; Matthew Hickman; Christian J Hopfer; Jouke Jan Hottenga; René S Kahn; Jaakko Kaprio; Tellervo Korhonen; Henry R Kranzler; Ken Krauter; Pol A C van Lier; Pamela A F Madden; Sarah E Medland; Michael C Neale; Wim H J Meeus; Grant W Montgomery; Ilja M Nolte; Albertine J Oldehinkel; Zdenka Pausova; Josep A Ramos-Quiroga; Vanesa Richarte; Richard J Rose; Jean Shin; Michael C Stallings; Tamara L Wall; Jennifer J Ware; Margaret J Wright; Hongyu Zhao; Hans M Koot; Tomas Paus; John K Hewitt; Marta Ribasés; Anu Loukola; Marco P Boks; Harold Snieder; Marcus R Munafò; Joel Gelernter; Dorret I Boomsma; Nicholas G Martin; Nathan A Gillespie; Jacqueline M Vink; Eske M Derks Journal: Addiction Date: 2018-08-19 Impact factor: 6.526