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7. Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms

Author

Jami, Eshim S, Hammerschlag, Anke R, Ip, Hill F, Allegrini, Andrea G, Benyamin, Beben, Border, Richard, Diemer, Elizabeth W, Jiang, Chang, Karhunen, Ville, Lu, Yi, Lu, Qing, Mallard, Travis T, Mishra, Pashupati P, Nolte, Ilja M, Palviainen, Teemu, Peterson, Roseann E, Sallis, Hannah M, Shabalin, Andrey A, Tate, Ashley E, Thiering, Elisabeth, Vilor-Tejedor, Natàlia, Wang, Carol, Zhou, Ang, Adkins, Daniel E, Alemany, Silvia, Ask, Helga, Chen, Qi, Corley, Robin P, Ehli, Erik A, Evans, Luke M, Havdahl, Alexandra, Hagenbeek, Fiona A, Hakulinen, Christian, Henders, Anjali K, Hottenga, Jouke Jan, Korhonen, Tellervo, Mamun, Abdullah, Marrington, Shelby, Neumann, Alexander, Rimfeld, Kaili, Rivadeneira, Fernando, Silberg, Judy L, van Beijsterveldt, Catharina E, Vuoksimaa, Eero, Whipp, Alyce M, Tong, Xiaoran, Andreassen, Ole A, Boomsma, Dorret I, Brown, Sandra A, Burt, S Alexandra, Copeland, William, Dick, Danielle M, Harden, K Paige, Harris, Kathleen Mullan, Hartman, Catharina A, Heinrich, Joachim, Hewitt, John K, Hopfer, Christian, Hypponen, Elina, Jarvelin, Marjo-Riitta, Kaprio, Jaakko, Keltikangas-Järvinen, Liisa, Klump, Kelly L, Krauter, Kenneth, Kuja-Halkola, Ralf, Larsson, Henrik, Lehtimäki, Terho, Lichtenstein, Paul, Lundström, Sebastian, Maes, Hermine H, Magnus, Per, Munafò, Marcus R, Najman, Jake M, Njølstad, Pål R, Oldehinkel, Albertine J, Pennell, Craig E, Plomin, Robert, Reichborn-Kjennerud, Ted, Reynolds, Chandra, Rose, Richard J, Smolen, Andrew, Snieder, Harold, Stallings, Michael, Standl, Marie, Sunyer, Jordi, Tiemeier, Henning, Wadsworth, Sally J, Wall, Tamara L, Whitehouse, Andrew JO, Williams, Gail M, Ystrøm, Eivind, Nivard, Michel G, Bartels, Meike, and Middeldorp, Christel M

Subjects
Biological Psychology, Psychology, Genetics, Pediatric, Brain Disorders, Serious Mental Illness, Mental Health, Human Genome, Depression, Mental Illness, Behavioral and Social Science, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Mental health, Adolescent, Adult, Aggression, Anxiety, Attention Deficit Disorder with Hyperactivity, Autistic Disorder, Bipolar Disorder, Child, Child, Preschool, Genome-Wide Association Study, Humans, Loneliness, Polymorphism, Single Nucleotide, Schizophrenia, Sleep Initiation and Maintenance Disorders, depression, anxiety, repeated measures, genetic epidemiology, molecular genetics, Medical and Health Sciences, Psychology and Cognitive Sciences, Developmental & Child Psychology, Clinical sciences, Paediatrics, Applied and developmental psychology
Abstract

ObjectiveTo investigate the genetic architecture of internalizing symptoms in childhood and adolescence.MethodIn 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument.ResultsThe meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg| = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa.ConclusionGenetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

Published
2022

9. IntEgrating Smoking Cessation treAtment into usual online Psychological care for people with common mEntal illness: Protocol for an online randomised feasibility and pilot study (ESCAPE digital)

Author

Blackwell, Anna K.M., Daryan, Shadi, Roy, Deborah, Duffy, Daniel, Hisler, Garrett, Sawyer, Katherine, Ainsworth, Ben, Richards, Derek, Hiscock, Douglas, Papadakis, Sophia, Brown, Jamie, Munafò, Marcus R., Jacobsen, Pamela, Aveyard, Paul, and Taylor, Gemma

Published
2024
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15. Consensus-based guidance for conducting and reporting multi-analyst studies

Author

Aczel, Balazs, Szaszi, Barnabas, Nilsonne, Gustav, van den Akker, Olmo R, Albers, Casper J, van Assen, Marcel ALM, Bastiaansen, Jojanneke A, Benjamin, Daniel, Boehm, Udo, Botvinik-Nezer, Rotem, Bringmann, Laura F, Busch, Niko A, Caruyer, Emmanuel, Cataldo, Andrea M, Cowan, Nelson, Delios, Andrew, van Dongen, Noah NN, Donkin, Chris, van Doorn, Johnny B, Dreber, Anna, Dutilh, Gilles, Egan, Gary F, Gernsbacher, Morton Ann, Hoekstra, Rink, Hoffmann, Sabine, Holzmeister, Felix, Huber, Juergen, Johannesson, Magnus, Jonas, Kai J, Kindel, Alexander T, Kirchler, Michael, Kunkels, Yoram K, Lindsay, D Stephen, Mangin, Jean-Francois, Matzke, Dora, Munafò, Marcus R, Newell, Ben R, Nosek, Brian A, Poldrack, Russell A, van Ravenzwaaij, Don, Rieskamp, Jörg, Salganik, Matthew J, Sarafoglou, Alexandra, Schonberg, Tom, Schweinsberg, Martin, Shanks, David, Silberzahn, Raphael, Simons, Daniel J, Spellman, Barbara A, St-Jean, Samuel, Starns, Jeffrey J, Uhlmann, Eric Luis, Wicherts, Jelte, and Wagenmakers, Eric-Jan

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Health Sciences, Consensus, Data Analysis, Datasets as Topic, Research, multi-analyst, metascience, statistical practice, science forum, expert consensus, analytical variability, None, medicine, neuroscience, none, Biochemistry and Cell Biology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Any large dataset can be analyzed in a number of ways, and it is possible that the use of different analysis strategies will lead to different results and conclusions. One way to assess whether the results obtained depend on the analysis strategy chosen is to employ multiple analysts and leave each of them free to follow their own approach. Here, we present consensus-based guidance for conducting and reporting such multi-analyst studies, and we discuss how broader adoption of the multi-analyst approach has the potential to strengthen the robustness of results and conclusions obtained from analyses of datasets in basic and applied research.

Published
2021

17. Genetic diversity fuels gene discovery for tobacco and alcohol use

Author

Saunders, Gretchen R. B., Wang, Xingyan, Chen, Fang, Jang, Seon-Kyeong, Liu, Mengzhen, Wang, Chen, Gao, Shuang, Jiang, Yu, Khunsriraksakul, Chachrit, Otto, Jacqueline M., Addison, Clifton, Akiyama, Masato, Albert, Christine M., Aliev, Fazil, Alonso, Alvaro, Arnett, Donna K., Ashley-Koch, Allison E., Ashrani, Aneel A., Barnes, Kathleen C., Barr, R. Graham, Bartz, Traci M., Becker, Diane M., Bielak, Lawrence F., Benjamin, Emelia J., Bis, Joshua C., Bjornsdottir, Gyda, Blangero, John, Bleecker, Eugene R., Boardman, Jason D., Boerwinkle, Eric, Boomsma, Dorret I., Boorgula, Meher Preethi, Bowden, Donald W., Brody, Jennifer A., Cade, Brian E., Chasman, Daniel I., Chavan, Sameer, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Iona, Cho, Michael H., Choquet, Hélène, Cole, John W., Cornelis, Marilyn C., Cucca, Francesco, Curran, Joanne E., de Andrade, Mariza, Dick, Danielle M., Docherty, Anna R., Duggirala, Ravindranath, Eaton, Charles B., Ehringer, Marissa A., Esko, Tõnu, Faul, Jessica D., Silva, Lilian Fernandes, Fiorillo, Edoardo, Fornage, Myriam, Freedman, Barry I., Gabrielsen, Maiken E., Garrett, Melanie E., Gharib, Sina A., Gieger, Christian, Gillespie, Nathan, Glahn, David C., Gordon, Scott D., Gu, Charles C., Gu, Dongfeng, Gudbjartsson, Daniel F., Guo, Xiuqing, Haessler, Jeffrey, Hall, Michael E., Haller, Toomas, Harris, Kathleen Mullan, He, Jiang, Herd, Pamela, Hewitt, John K., Hickie, Ian, Hidalgo, Bertha, Hokanson, John E., Hopfer, Christian, Hottenga, JoukeJan, Hou, Lifang, Huang, Hongyan, Hung, Yi-Jen, Hunter, David J., Hveem, Kristian, Hwang, Shih-Jen, Hwu, Chii-Min, Iacono, William, Irvin, Marguerite R., Jee, Yon Ho, Johnson, Eric O., Joo, Yoonjung Y., Jorgenson, Eric, Justice, Anne E., Kamatani, Yoichiro, Kaplan, Robert C., Kaprio, Jaakko, Kardia, Sharon L. R., Keller, Matthew C., Kelly, Tanika N., Kooperberg, Charles, Korhonen, Tellervo, Kraft, Peter, Krauter, Kenneth, Kuusisto, Johanna, Laakso, Markku, Lasky-Su, Jessica, Lee, Wen-Jane, Lee, James J., Levy, Daniel, Li, Liming, Li, Kevin, Li, Yuqing, Lin, Kuang, Lind, Penelope A., Liu, Chunyu, Lloyd-Jones, Donald M., Lutz, Sharon M., Ma, Jiantao, Mägi, Reedik, Manichaikul, Ani, Martin, Nicholas G., Mathur, Ravi, Matoba, Nana, McArdle, Patrick F., McGue, Matt, McQueen, Matthew B., Medland, Sarah E., Metspalu, Andres, Meyers, Deborah A., Millwood, Iona Y., Mitchell, Braxton D., Mohlke, Karen L., Moll, Matthew, Montasser, May E., Morrison, Alanna C., Mulas, Antonella, Nielsen, Jonas B., North, Kari E., Oelsner, Elizabeth C., Okada, Yukinori, Orrù, Valeria, Palmer, Nicholette D., Palviainen, Teemu, Pandit, Anita, Park, S. Lani, Peters, Ulrike, Peters, Annette, Peyser, Patricia A., Polderman, Tinca J. C., Rafaels, Nicholas, Redline, Susan, Reed, Robert M., Reiner, Alex P., Rice, John P., Rich, Stephen S., Richmond, Nicole E., Roan, Carol, Rotter, Jerome I., Rueschman, Michael N., Runarsdottir, Valgerdur, Saccone, Nancy L., Schwartz, David A., Shadyab, Aladdin H., Shi, Jingchunzi, Shringarpure, Suyash S., Sicinski, Kamil, Skogholt, Anne Heidi, Smith, Jennifer A., Smith, Nicholas L., Sotoodehnia, Nona, Stallings, Michael C., Stefansson, Hreinn, Stefansson, Kari, Stitzel, Jerry A., Sun, Xiao, Syed, Moin, Tal-Singer, Ruth, Taylor, Amy E., Taylor, Kent D., Telen, Marilyn J., Thai, Khanh K., Tiwari, Hemant, Turman, Constance, Tyrfingsson, Thorarinn, Wall, Tamara L., Walters, Robin G., Weir, David R., Weiss, Scott T., White, Wendy B., Whitfield, John B., Wiggins, Kerri L., Willemsen, Gonneke, Willer, Cristen J., Winsvold, Bendik S., Xu, Huichun, Yanek, Lisa R., Yin, Jie, Young, Kristin L., Young, Kendra A., Yu, Bing, Zhao, Wei, Zhou, Wei, Zöllner, Sebastian, Zuccolo, Luisa, Batini, Chiara, Bergen, Andrew W., Bierut, Laura J., David, Sean P., Gagliano Taliun, Sarah A., Hancock, Dana B., Jiang, Bibo, Munafò, Marcus R., Thorgeirsson, Thorgeir E., Liu, Dajiang J., and Vrieze, Scott

Published
2022
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18. Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis

Author

Tielbeek, Jorim J., Uffelmann, Emil, Williams, Benjamin S., Colodro-Conde, Lucía, Gagnon, Éloi, Mallard, Travis T., Levitt, Brandt E., Jansen, Philip R., Johansson, Ada, Sallis, Hannah M., Pistis, Giorgio, Saunders, Gretchen R. B., Allegrini, Andrea G., Rimfeld, Kaili, Konte, Bettina, Klein, Marieke, Hartmann, Annette M., Salvatore, Jessica E., Nolte, Ilja M., Demontis, Ditte, Malmberg, Anni L. K., Burt, S. Alexandra, Savage, Jeanne E., Sugden, Karen, Poulton, Richie, Harris, Kathleen Mullan, Vrieze, Scott, McGue, Matt, Iacono, William G., Mota, Nina Roth, Mill, Jonathan, Viana, Joana F., Mitchell, Brittany L., Morosoli, Jose J., Andlauer, Till F. M., Ouellet-Morin, Isabelle, Tremblay, Richard E., Côté, Sylvana M., Gouin, Jean-Philippe, Brendgen, Mara R., Dionne, Ginette, Vitaro, Frank, Lupton, Michelle K., Martin, Nicholas G., Castelao, Enrique, Räikkönen, Katri, Eriksson, Johan G., Lahti, Jari, Hartman, Catharina A., Oldehinkel, Albertine J., Snieder, Harold, Liu, Hexuan, Preisig, Martin, Whipp, Alyce, Vuoksimaa, Eero, Lu, Yi, Jern, Patrick, Rujescu, Dan, Giegling, Ina, Palviainen, Teemu, Kaprio, Jaakko, Harden, Kathryn Paige, Munafò, Marcus R., Morneau-Vaillancourt, Geneviève, Plomin, Robert, Viding, Essi, Boutwell, Brian B., Aliev, Fazil, Dick, Danielle M., Popma, Arne, Faraone, Stephen V., Børglum, Anders D., Medland, Sarah E., Franke, Barbara, Boivin, Michel, Pingault, Jean-Baptiste, Glennon, Jeffrey C., Barnes, J. C., Fisher, Simon E., Moffitt, Terrie E., Caspi, Avshalom, Polderman, Tinca J. C., and Posthuma, Danielle

Published
2022
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20. Author Correction: GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability

Author

Pasman, Joëlle A, Verweij, Karin JH, Gerring, Zachary, Stringer, Sven, Sanchez-Roige, Sandra, Treur, Jorien L, Abdellaoui, Abdel, Nivard, Michel G, Baselmans, Bart ML, Ong, Jue-Sheng, Ip, Hill F, van der Zee, Matthijs D, Bartels, Meike, Day, Felix R, Fontanillas, Pierre, Elson, Sarah L, de Wit, Harriet, Davis, Lea K, MacKillop, James, Derringer, Jaime L, Branje, Susan JT, Hartman, Catharina A, Heath, Andrew C, van Lier, Pol AC, Madden, Pamela AF, Mägi, Reedik, Meeus, Wim, Montgomery, Grant W, Oldehinkel, AJ, Pausova, Zdenka, Ramos-Quiroga, Josep A, Paus, Tomas, Ribases, Marta, Kaprio, Jaakko, Boks, Marco PM, Bell, Jordana T, Spector, Tim D, Gelernter, Joel, Boomsma, Dorret I, Martin, Nicholas G, MacGregor, Stuart, Perry, John RB, Palmer, Abraham A, Posthuma, Danielle, Munafò, Marcus R, Gillespie, Nathan A, Derks, Eske M, and Vink, Jacqueline M

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Drug Abuse (NIDA only), Human Genome, Brain Disorders, Serious Mental Illness, Genetics, Schizophrenia, Substance Misuse, Mental Health, 2.1 Biological and endogenous factors, Aetiology, Mental health, 23andMe Research Team, Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Neurosciences, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Several occurrences of the word 'schizophrenia' have been re-worded as 'liability to schizophrenia' or 'schizophrenia risk', including in the title, which should have been "GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability," as well as in Supplementary Figures 1-10 and Supplementary Tables 7-10, to more accurately reflect the findings of the work.

Published
2019

22. Applying Mendelian randomization to appraise causality in relationships between nutrition and cancer

Author

Wade, Kaitlin H., Yarmolinsky, James, Giovannucci, Edward, Lewis, Sarah J., Millwood, Iona Y., Munafò, Marcus R., Meddens, Fleur, Burrows, Kimberley, Bell, Joshua A., Davies, Neil M., Mariosa, Daniela, Kanerva, Noora, Vincent, Emma E., Smith-Byrne, Karl, Guida, Florence, Gunter, Marc J., Sanderson, Eleanor, Dudbridge, Frank, Burgess, Stephen, Cornelis, Marilyn C., Richardson, Tom G., Borges, Maria Carolina, Bowden, Jack, Hemani, Gibran, Cho, Yoonsu, Spiller, Wes, Richmond, Rebecca C., Carter, Alice R., Langdon, Ryan, Lawlor, Deborah A., Walters, Robin G., Vimaleswaran, Karani Santhanakrishnan, Anderson, Annie, Sandu, Meda R., Tilling, Kate, Davey Smith, George, Martin, Richard M., and Relton, Caroline L.

Published
2022
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23. Overview of CAPICE—Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe—an EU Marie Skłodowska-Curie International Training Network

Author

Rajula, Hema Sekhar Reddy, Manchia, Mirko, Agarwal, Kratika, Akingbuwa, Wonuola A., Allegrini, Andrea G., Diemer, Elizabeth, Doering, Sabrina, Haan, Elis, Jami, Eshim S., Karhunen, Ville, Leone, Marica, Schellhas, Laura, Thompson, Ashley, van den Berg, Stéphanie M., Bergen, Sarah E., Kuja-Halkola, Ralf, Hammerschlag, Anke R., Järvelin, Marjo Riitta, Leval, Amy, Lichtenstein, Paul, Lundstrom, Sebastian, Mauri, Matteo, Munafò, Marcus R., Myers, David, Plomin, Robert, Rimfeld, Kaili, Tiemeier, Henning, Ystrom, Eivind, Fanos, Vassilios, Bartels, Meike, and Middeldorp, Christel M.

Published
2022
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24. Grassroots Training for Reproducible Science: A Consortium-Based Approach to the Empirical Dissertation

Author

Button, Katherine S., Chambers, Christopher D., Lawrence, Natalia, and Munafò, Marcus R.

Abstract

There is a widely acknowledged need to improve the reliability and efficiency of scientific research to increase the credibility of the published scientific literature and accelerate discovery. Widespread improvement requires a cultural shift in both thinking and practice, and better education will be instrumental to achieve this. Here we argue that education in reproducible science should start at the grassroots. We present our model of consortium-based student projects to train undergraduates in reproducible team science. We discuss how with careful design we have aligned collaboration with the current conventions for individual student assessment. We reflect on our experiences of several years running the GW4 Undergraduate Psychology Consortium offering insights we hope will be of practical use to others wishing to adopt a similar approach. We consider the pedagogical benefits of our approach in equipping students with 21st-century skills. Finally, we reflect on the need to shift incentives to reward to team science in global research and how this applies to the reward structures of student assessment.

Published
2020
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25. Genome‐wide association meta‐analysis of age at first cannabis use

Author

Minică, Camelia C, Verweij, Karin JH, van der Most, Peter J, Mbarek, Hamdi, Bernard, Manon, van Eijk, Kristel R, Lind, Penelope A, Liu, Meng Zhen, Maciejewski, Dominique F, Palviainen, Teemu, Sánchez‐Mora, Cristina, Sherva, Richard, Taylor, Michelle, Walters, Raymond K, Abdellaoui, Abdel, Bigdeli, Timothy B, Branje, Susan JT, Brown, Sandra A, Casas, Miguel, Corley, Robin P, Davey‐Smith, George, Davies, Gareth E, Ehli, Erik A, Farrer, Lindsay, Fedko, Iryna O, Garcia‐Martínez, Iris, Gordon, Scott D, Hartman, Catharina A, Heath, Andrew C, Hickie, Ian B, Hickman, Matthew, Hopfer, Christian J, Hottenga, Jouke Jan, Kahn, René S, Kaprio, Jaakko, Korhonen, Tellervo, Kranzler, Henry R, Krauter, Ken, van Lier, Pol AC, Madden, Pamela AF, Medland, Sarah E, Neale, Michael C, Meeus, Wim HJ, Montgomery, Grant W, Nolte, Ilja M, Oldehinkel, Albertine J, Pausova, Zdenka, Ramos‐Quiroga, Josep A, Richarte, Vanesa, Rose, Richard J, Shin, Jean, Stallings, Michael C, Wall, Tamara L, Ware, Jennifer J, Wright, Margaret J, Zhao, Hongyu, Koot, Hans M, Paus, Tomas, Hewitt, John K, Ribasés, Marta, Loukola, Anu, Boks, Marco P, Snieder, Harold, Munafò, Marcus R, Gelernter, Joel, Boomsma, Dorret I, Martin, Nicholas G, Gillespie, Nathan A, Vink, Jacqueline M, and Derks, Eske M

Subjects
Biological Psychology, Epidemiology, Health Sciences, Psychology, Cannabinoid Research, Substance Misuse, Brain Disorders, Human Genome, Clinical Research, Prevention, Drug Abuse (NIDA only), Pediatric, Genetics, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Adolescent, Adult, Age of Onset, Calcium-Transporting ATPases, Female, Genome-Wide Association Study, Humans, Male, Marijuana Use, Middle Aged, Polymorphism, Single Nucleotide, Twins, Young Adult, Age at first use, ATP2C2, cannabis initiation, genome-wide association, heritability, substance use, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Public health, Clinical and health psychology
Abstract

Background and aimsCannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants.MethodsA twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals.ResultsThe twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19-60%]. Shared and unique environmental factors explained 39% (95% CI = 20-56%) and 22% (95% CI = 16-29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P  0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant.ConclusionAge at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

Published
2018

26. GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability

Author

Pasman, Joëlle A, Verweij, Karin JH, Gerring, Zachary, Stringer, Sven, Sanchez-Roige, Sandra, Treur, Jorien L, Abdellaoui, Abdel, Nivard, Michel G, Baselmans, Bart ML, Ong, Jue-Sheng, Ip, Hill F, van der Zee, Matthijs D, Bartels, Meike, Day, Felix R, Fontanillas, Pierre, Elson, Sarah L, the 23andMe Research Team, de Wit, Harriet, Davis, Lea K, MacKillop, James, The Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Derringer, Jaime L, Branje, Susan JT, Hartman, Catharina A, Heath, Andrew C, van Lier, Pol AC, Madden, Pamela AF, Mägi, Reedik, Meeus, Wim, Montgomery, Grant W, Oldehinkel, AJ, Pausova, Zdenka, Ramos-Quiroga, Josep A, Paus, Tomas, Ribases, Marta, Kaprio, Jaakko, Boks, Marco PM, Bell, Jordana T, Spector, Tim D, Gelernter, Joel, Boomsma, Dorret I, Martin, Nicholas G, MacGregor, Stuart, Perry, John RB, Palmer, Abraham A, Posthuma, Danielle, Munafò, Marcus R, Gillespie, Nathan A, Derks, Eske M, and Vink, Jacqueline M

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Behavioral and Social Science, Human Genome, Prevention, Serious Mental Illness, Brain Disorders, Clinical Research, Schizophrenia, Women's Health, Drug Abuse (NIDA only), Cannabinoid Research, Mental Health, Substance Misuse, Genetics, Mental Illness, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Cell Adhesion Molecules, Databases, Genetic, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Marijuana Abuse, Mendelian Randomization Analysis, Middle Aged, Polymorphism, Single Nucleotide, Risk-Taking, Young Adult, 23andMe Research Team, Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Neurosciences, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.

Published
2018

27. GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia.

Author

Pasman, Joëlle A, Verweij, Karin JH, Gerring, Zachary, Stringer, Sven, Sanchez-Roige, Sandra, Treur, Jorien L, Abdellaoui, Abdel, Nivard, Michel G, Baselmans, Bart ML, Ong, Jue-Sheng, Ip, Hill F, van der Zee, Matthijs D, Bartels, Meike, Day, Felix R, Fontanillas, Pierre, Elson, Sarah L, 23andMe Research Team, de Wit, Harriet, Davis, Lea K, MacKillop, James, Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Derringer, Jaime L, Branje, Susan JT, Hartman, Catharina A, Heath, Andrew C, van Lier, Pol AC, Madden, Pamela AF, Mägi, Reedik, Meeus, Wim, Montgomery, Grant W, Oldehinkel, AJ, Pausova, Zdenka, Ramos-Quiroga, Josep A, Paus, Tomas, Ribases, Marta, Kaprio, Jaakko, Boks, Marco PM, Bell, Jordana T, Spector, Tim D, Gelernter, Joel, Boomsma, Dorret I, Martin, Nicholas G, MacGregor, Stuart, Perry, John RB, Palmer, Abraham A, Posthuma, Danielle, Munafò, Marcus R, Gillespie, Nathan A, Derks, Eske M, and Vink, Jacqueline M

Subjects
23andMe Research Team, Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Humans, Marijuana Abuse, Genetic Predisposition to Disease, Cell Adhesion Molecules, Risk-Taking, Mental Health, Schizophrenia, Gene Expression Regulation, Genotype, Polymorphism, Single Nucleotide, Databases, Genetic, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Genome-Wide Association Study, Young Adult, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Databases, Genetic, and over, Prevention, Human Genome, Brain Disorders, Drug Abuse, Substance Abuse, Genetics, Clinical Research, 2.1 Biological and endogenous factors, Cardiovascular, Neurology & Neurosurgery, Neurosciences, Cognitive Sciences, Psychology
Abstract

Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.

Published
2018

29. Mendelian randomization

Author

Sanderson, Eleanor, Glymour, M. Maria, Holmes, Michael V., Kang, Hyunseung, Morrison, Jean, Munafò, Marcus R., Palmer, Tom, Schooling, C. Mary, Wallace, Chris, Zhao, Qingyuan, and Davey Smith, George

Published
2022
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30. Investigating the effect of sexual behaviour on oropharyngeal cancer risk: a methodological assessment of Mendelian randomization

Author

Gormley, Mark, Dudding, Tom, Kachuri, Linda, Burrows, Kimberley, Chong, Amanda H. W., Martin, Richard M., Thomas, Steven J., Tyrrell, Jessica, Ness, Andrew R., Brennan, Paul, Munafò, Marcus R., Pring, Miranda, Boccia, Stefania, Olshan, Andrew F., Diergaarde, Brenda, Hung, Rayjean J., Liu, Geoffrey, Tajara, Eloiza H., Severino, Patricia, Toporcov, Tatiana N., Lacko, Martin, Waterboer, Tim, Brenner, Nicole, Smith, George Davey, Vincent, Emma E., and Richmond, Rebecca C.

Published
2022
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34. Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes

Author

Chen, Jingchun, Loukola, Anu, Gillespie, Nathan A., Peterson, Roseann, Jia, Peilin, Riley, Brien, Maes, Hermine, Dick, Daniella M., Kendler, Kenneth S., Damaj, M. Imad, Miles, Michael F., Zhao, Zhongming, Li, Ming D., Vink, Jacqueline M., Minica, Camelia C., Willemsen, Gonneke, Boomsma, Dorret I., Qaiser, Beenish, Madden, Pamela A. F., Korhonen, Tellervo, Jousilahti, Pekka, Hällfors, Jenni, Gelernter, Joel, Kranzler, Henry R., Sherva, Richard, Farrer, Lindsay, Maher, Brion, Vanyukov, Michael, Taylor, Michelle, Ware, Jenifer J., Munafò, Marcus R., Lutz, Sharon M., Hokanson, John E., Gu, Fangyi, Landi, Maria T., Caporaso, Neil E., Hancock, Dana B., Gaddis, Nathan C., Baker, Timothy B., Bierut, Laura J., Johnson, Eric O., Chenoweth, Meghan, Lerman, Caryn, Tyndale, Rachel, Kaprio, Jaakko, and Chen, Xiangning

Published
2020

42. Impaired Recognition of Basic Emotions from Facial Expressions in Young People with Autism Spectrum Disorder: Assessing the Importance of Expression Intensity

Author

Griffiths, Sarah, Jarrold, Christopher, Penton-Voak, Ian S., Woods, Andy T., Skinner, Andy L., and Munafò, Marcus R.

Abstract

It has been proposed that impairments in emotion recognition in ASD are greater for more subtle expressions of emotion. We measured recognition of 6 basic facial expressions at 8 intensity levels in young people (6-16 years) with ASD (N = 63) and controls (N = 64) via an Internet platform. Participants with ASD were less accurate than controls at labelling expressions across intensity levels, although differences at very low levels were not detected due to floor effects. Recognition accuracy did not correlate with parent-reported social functioning in either group. These findings provide further evidence for an impairment in recognition of basic emotion in ASD and do not support the idea that this impairment is limited solely to low intensity expressions.

Published
2019
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43. Impact on alcohol selection and online purchasing of changing the proportion of available non-alcoholic versus alcoholic drinks: A randomised controlled trial

Author

Clarke, Natasha, Blackwell, Anna K. M., Ferrar, Jennifer, De-Loyde, Katie, Pilling, Mark A., Munafò, Marcus R., Marteau, Theresa M., and Hollands, Gareth J.

Subjects
Drinking of alcoholic beverages -- Health aspects -- Social aspects, Beverages -- Purchasing, Consumer behavior -- Analysis, Biological sciences
Abstract

Background Increasing the availability of non-alcoholic options is a promising population-level intervention to reduce alcohol consumption, currently unassessed in naturalistic settings. This study in an online retail context aimed to estimate the impact of increasing the proportion of non-alcoholic (relative to alcoholic) drinks, on selection and purchasing of alcohol. Methods and results Adults (n = 737) residing in England and Wales who regularly purchased alcohol online were recruited between March and July 2021. Participants were randomly assigned to one of 3 groups: '25% non-alcoholic/75% alcoholic'; '50% non-alcoholic/50% alcoholic'; and '75% non-alcoholic/25% alcoholic,' then selected drinks in a simulated online supermarket, before purchasing them in an actual online supermarket. The primary outcome was the number of alcohol units selected (with intention to purchase); secondary outcomes included actual purchasing. A total of 607 participants (60% female, mean age = 38 years [range: 18 to 76]) completed the study and were included in the primary analysis. In the first part of a hurdle model, a greater proportion of participants in the '75% non-alcoholic' group did not select any alcohol (13.1%) compared to the '25% non-alcoholic' group (3.4%; 95% confidence interval [CI] -2.09, -0.63; p < 0.001). There was no evidence of a difference between the '75% non-alcoholic' and the '50% non-alcoholic' (7.2%) groups (95% CI 0.10, 1.34; p = 0.022) or between the '50% non-alcoholic' and the '25% non-alcoholic' groups (95% CI -1.44, 0.17; p = 0.121). In the second part of a hurdle model in participants (559/607) selecting any drinks containing alcohol, the '75% non-alcoholic' group selected fewer alcohol units compared to the '50% non-alcoholic' (95% CI -0.44, -0.14; p < 0.001) and '25% non-alcoholic' (95% CI -0.54, -0.24; p < 0.001) groups, with no evidence of a difference between the '50% non-alcoholic' and '25% non-alcoholic' groups (95% CI -0.24, 0.05; p = 0.178). Overall, across all participants, 17.46 units (95% CI 15.24, 19.68) were selected in the '75% non-alcoholic' group; 25.51 units (95% CI 22.60, 28.43) in the '50% non-alcoholic' group; and 29.40 units (95% CI 26.39, 32.42) in the '25% non-alcoholic' group. This corresponds to 8.1 fewer units (a 32% reduction) in the '75% non-alcoholic' compared to the '50% non-alcoholic' group, and 11.9 fewer alcohol units (41% reduction) compared to the '25% non-alcoholic' group; 3.9 fewer units (13% reduction) were selected in the '50% non-alcoholic' group than in the '25% non-alcoholic' group. For all other outcomes, alcohol selection and purchasing were consistently lowest in the '75% non-alcoholic' group. Study limitations include the setting not being entirely naturalistic due to using a simulated online supermarket as well as an actual online supermarket, and that there was substantial dropout between selection and purchasing. Conclusions This study provides evidence that substantially increasing the proportion of non-alcoholic drinks-from 25% to 50% or 75%-meaningfully reduces alcohol selection and purchasing. Further studies are warranted to assess whether these effects are realised in a range of real-world settings. Trial registration ISRCTN: 11004483; OSF: https://osf.io/qfupw., Author(s): Natasha Clarke 1,2,*, Anna K. M. Blackwell 3,4, Jennifer Ferrar 3, Katie De-Loyde 3, Mark A. Pilling 1, Marcus R. Munafò 3, Theresa M. Marteau 1,*, Gareth J. Hollands [...]

Published
2023
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44. Do Flavor Descriptions Influence Subjective Ratings of Flavored and Unflavored E-liquids Among Nonsmoking and Non-vaping UK Adolescents?

Author

Dyer, Maddy L, Suddell, Steph F, Khouja, Jasmine N, Havill, Michelle A, Blackwell, Anna K M, Maynard, Olivia M, Munafò, Marcus R, and Attwood, Angela S

Subjects
FRUIT flavors & odors, ELECTRONIC cigarettes, TOBACCO smoke, SMOKING, ADULTS
Abstract

Introduction Youth use of electronic cigarettes (e-cigarettes) is rising globally and is associated with health harms. Flavor descriptions on e-liquid packaging may contribute to the appeal of e-cigarettes among youth. This study compared subjective ratings of e-liquid packaging flavor descriptions among nonsmoking and non-vaping UK adolescents. Aims and Methods This was an online observational study in a UK sample of nonsmoking and non-vaping adolescents aged 11–17 years. The primary analyses compared flavored versus unflavored descriptions and the secondary analyses compared sweet flavor versus fruit flavor descriptions. Outcomes were packaging appraisal, packaging receptivity, perceived harm, and perceived audience. Results The survey was completed by 120 participants (74% female). Packaging appraisal ratings were higher for e-liquids with flavored descriptions than unflavored descriptions (mean difference 5.9, 95% CI: 4.2 to 7.6, p  < .001). Similarly, packaging receptivity ratings were higher for e-liquids with flavored descriptions than unflavored descriptions (mean difference 4.2, 95% CI: 2.8 to 5.6, p  < .001). Participants also perceived e-liquids with flavored (vs. unflavored) descriptions as less "grown-up" (mean difference −5.2, 95% CI: −7.3 to −3.1, p  < .001). However, ratings of perceived harm were similar for flavored and unflavored descriptions (mean difference −1.0, 95% CI: −2.6 to.5, p  = .189). Conclusions Although this study found differences in subjective ratings of e-liquids with flavored and unflavored descriptions, nonsmoking and non-vaping UK adolescents generally had low appraisal and receptivity for e-liquids and they perceived them as being "grown-up" and harmful. Implications Youth use of electronic cigarettes (e-cigarettes) is increasing globally, leading to concerns about health harms. This study compared adolescents' ratings of e-liquids with flavored versus unflavored descriptions and e-liquids with sweet flavor versus fruit flavor descriptions. This study adds to previous studies that have compared adolescents' ratings of e-liquids with tobacco flavor versus non-tobacco flavor descriptions. Although packaging appraisal and receptivity ratings were higher (more positive) for e-liquids with flavored versus unflavored descriptions, overall, adolescents who do not smoke or vape had low appraisal and receptivity for e-liquids, and they perceived them as being "grown-up" and harmful. [ABSTRACT FROM AUTHOR]

Published
2024
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49. Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts

Author

Schwantes-An, Tae-Hwi, Zhang, Juan, Chen, Li-Shiun, Hartz, Sarah M, Culverhouse, Robert C, Chen, Xiangning, Coon, Hilary, Frank, Josef, Kamens, Helen M, Konte, Bettina, Kovanen, Leena, Latvala, Antti, Legrand, Lisa N, Maher, Brion S, Melroy, Whitney E, Nelson, Elliot C, Reid, Mark W, Robinson, Jason D, Shen, Pei-Hong, Yang, Bao-Zhu, Andrews, Judy A, Aveyard, Paul, Beltcheva, Olga, Brown, Sandra A, Cannon, Dale S, Cichon, Sven, Corley, Robin P, Dahmen, Norbert, Degenhardt, Louisa, Foroud, Tatiana, Gaebel, Wolfgang, Giegling, Ina, Glatt, Stephen J, Grucza, Richard A, Hardin, Jill, Hartmann, Annette M, Heath, Andrew C, Herms, Stefan, Hodgkinson, Colin A, Hoffmann, Per, Hops, Hyman, Huizinga, David, Ising, Marcus, Johnson, Eric O, Johnstone, Elaine, Kaneva, Radka P, Kendler, Kenneth S, Kiefer, Falk, Kranzler, Henry R, Krauter, Ken S, Levran, Orna, Lucae, Susanne, Lynskey, Michael T, Maier, Wolfgang, Mann, Karl, Martin, Nicholas G, Mattheisen, Manuel, Montgomery, Grant W, Müller-Myhsok, Bertram, Murphy, Michael F, Neale, Michael C, Nikolov, Momchil A, Nishita, Denise, Nöthen, Markus M, Nurnberger, John, Partonen, Timo, Pergadia, Michele L, Reynolds, Maureen, Ridinger, Monika, Rose, Richard J, Rouvinen-Lagerström, Noora, Scherbaum, Norbert, Schmäl, Christine, Soyka, Michael, Stallings, Michael C, Steffens, Michael, Treutlein, Jens, Tsuang, Ming, Wall, Tamara L, Wodarz, Norbert, Yuferov, Vadim, Zill, Peter, Bergen, Andrew W, Chen, Jingchun, Cinciripini, Paul M, Edenberg, Howard J, Ehringer, Marissa A, Ferrell, Robert E, Gelernter, Joel, Goldman, David, Hewitt, John K, Hopfer, Christian J, Iacono, William G, Kaprio, Jaakko, Kreek, Mary Jeanne, Kremensky, Ivo M, Madden, Pamela AF, McGue, Matt, Munafò, Marcus R, and Philibert, Robert A

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Drug Abuse (NIDA only), Substance Misuse, Brain Disorders, Neurosciences, Genetics, Mental health, Good Health and Well Being, Adolescent, Adult, Alleles, Case-Control Studies, Child, Cohort Studies, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Polymorphism, Single Nucleotide, Receptors, Opioid, mu, Sample Size, Substance-Related Disorders, White People, Addiction, Substance dependence, OPRM1, Opioid receptor, Single nucleotide polymorphism, Genetic association, Zoology, Genetics & Heredity, Biomedical and clinical sciences, Health sciences
Abstract

The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83-0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses.

Published
2016

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