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1. Shared genetic risk between eating disorder‐ and substance‐use‐related phenotypes: Evidence from genome‐wide association studies

Author

Munn‐Chernoff, Melissa A, Johnson, Emma C, Chou, Yi‐Ling, Coleman, Jonathan RI, Thornton, Laura M, Walters, Raymond K, Yilmaz, Zeynep, Baker, Jessica H, Hübel, Christopher, Gordon, Scott, Medland, Sarah E, Watson, Hunna J, Gaspar, Héléna A, Bryois, Julien, Hinney, Anke, Leppä, Virpi M, Mattheisen, Manuel, Ripke, Stephan, Yao, Shuyang, Giusti‐Rodríguez, Paola, Hanscombe, Ken B, Adan, Roger AH, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A, Berrettini, Wade H, Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D, Courtet, Philippe, Crow, Scott, Crowley, James J, Danner, Unna N, Davis, Oliver SP, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E, Dick, Danielle M, Dikeos, Dimitris, Dina, Christian, Dmitrzak‐Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E, Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández‐Aranda, Fernando, Fichter, Manfred M, Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas J, Forzan, Monica, Franklin, Christopher S, Gallinger, Steven, Giegling, Ina, Giuranna, Johanna, Gonidakis, Fragiskos, Gorwood, Philip, Mayora, Monica Gratacos, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske G, Herms, Stefan, Herpertz‐Dahlmann, Beate, Herzog, Wolfgang, Huckins, Laura M, Hudson, James I, Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez‐Murcia, Susana, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Karhunen, Leila, Karwautz, Andreas, Kas, Martien JH, Kennedy, James L, Keski‐Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl‐Ri, Klump, Kelly L, Knudsen, Gun Peggy S, and La Via, Maria C

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Epidemiology, Health Sciences, Psychology, Pharmacology and Pharmaceutical Sciences, Nutrition, Brain Disorders, Alcoholism, Alcohol Use and Health, Mental Health, Eating Disorders, Substance Misuse, Genetics, Tobacco Smoke and Health, Tobacco, Human Genome, Drug Abuse (NIDA only), Prevention, Clinical Research, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Good Health and Well Being, Alcoholism, Depressive Disorder, Major, Feeding and Eating Disorders, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Schizophrenia, Substance-Related Disorders, Tobacco Use Disorder, eating disorders, genetic correlation, substance use, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Biomedical and clinical sciences, Health sciences
Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.

Published
2021

3. The etiology of DSM-5 alcohol use disorder: Evidence of shared and non-shared additive genetic effects

Author

Palmer, Rohan HC, Brick, Leslie A, Chou, Yi-Ling, Agrawal, Arpana, McGeary, John E, Heath, Andrew C, Bierut, Laura, Keller, Matthew C, Johnson, Eric, Hartz, Sarah M, Schuckit, Marc A, and Knopik, Valerie S

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Substance Misuse, Genetic Testing, Mental Health, Brain Disorders, Alcoholism, Alcohol Use and Health, Human Genome, Mental health, Good Health and Well Being, Adult, Alcoholism, Diagnostic and Statistical Manual of Mental Disorders, Female, Genomics, Humans, Male, Middle Aged, Phenotype, Alcohol use disorder, Heritability, DSM-5, European, Ancestry, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Biochemistry and cell biology, Pharmacology and pharmaceutical sciences, Epidemiology
Abstract

BackgroundAlcoholism is a multifactorial disorder influenced by multiple gene loci, each with small effect. Studies suggest shared genetic influences across DSM-IV alcohol dependence symptoms, but shared effects across DSM-5 alcohol use disorder remains unknown. We aimed to test the assumption of genetic homogeneity across the 11 criteria of DSM-5 alcohol use disorder (AUD).MethodsData from 2596 alcohol using individuals of European ancestry from the Study of Addiction: Genetics and Environment were used to examine the genomewide SNP-heritability (h2SNP) and SNP-covariance (rGSNP) between 11 DSM-5 AUD symptoms. Phenotypic relationships between symptoms were examined to confirm an underlying liability of AUD and the SNP-heritability of the observed latent trait and the co-heritabilityamong AUD symptoms was assessed using Genomic-Relatedness-Matrix-Restricted-Maximum-Likelihood. Genetic covariance among symptoms was examined using factor analysis.ResultsPhenotypic relationships confirmed a unidimensional underlying liability to AUD. Factor and parallel analyses of the observed genetic variance/covariance provided evidence of genetic homogeneity. Additive genetic effects on DSM-5 AUD symptoms varied from 0.10 to 0.37 and largely overlapped (rG-SNP across symptoms ranged from 0.49 - 0.92). The additive genetic effect on the DSM-5 AUD factor was 0.36, 0.14 for DSM-5 AUD diagnosis, and was 0.22 for DSM-5 AUD severity.ConclusionsCommon genetic variants influence DSM-5 AUD symptoms. Despite evidence for a common AUD factor, the evidence of only partially overlapping genetic effects across AUD symptoms further substantiates the need to simultaneously model common and symptom-specific genetic effects in molecular genetic studies in order to best characterize the genetic liability.

Published
2019

4. Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

Author

Walters, Raymond K, Polimanti, Renato, Johnson, Emma C, McClintick, Jeanette N, Adams, Mark J, Adkins, Amy E, Aliev, Fazil, Bacanu, Silviu-Alin, Batzler, Anthony, Bertelsen, Sarah, Biernacka, Joanna M, Bigdeli, Tim B, Chen, Li-Shiun, Clarke, Toni-Kim, Chou, Yi-Ling, Degenhardt, Franziska, Docherty, Anna R, Edwards, Alexis C, Fontanillas, Pierre, Foo, Jerome C, Fox, Louis, Frank, Josef, Giegling, Ina, Gordon, Scott, Hack, Laura M, Hartmann, Annette M, Hartz, Sarah M, Heilmann-Heimbach, Stefanie, Herms, Stefan, Hodgkinson, Colin, Hoffmann, Per, Jan Hottenga, Jouke, Kennedy, Martin A, Alanne-Kinnunen, Mervi, Konte, Bettina, Lahti, Jari, Lahti-Pulkkinen, Marius, Lai, Dongbing, Ligthart, Lannie, Loukola, Anu, Maher, Brion S, Mbarek, Hamdi, McIntosh, Andrew M, McQueen, Matthew B, Meyers, Jacquelyn L, Milaneschi, Yuri, Palviainen, Teemu, Pearson, John F, Peterson, Roseann E, Ripatti, Samuli, Ryu, Euijung, Saccone, Nancy L, Salvatore, Jessica E, Sanchez-Roige, Sandra, Schwandt, Melanie, Sherva, Richard, Streit, Fabian, Strohmaier, Jana, Thomas, Nathaniel, Wang, Jen-Chyong, Webb, Bradley T, Wedow, Robbee, Wetherill, Leah, Wills, Amanda G, Boardman, Jason D, Chen, Danfeng, Choi, Doo-Sup, Copeland, William E, Culverhouse, Robert C, Dahmen, Norbert, Degenhardt, Louisa, Domingue, Benjamin W, Elson, Sarah L, Frye, Mark A, Gäbel, Wolfgang, Hayward, Caroline, Ising, Marcus, Keyes, Margaret, Kiefer, Falk, Kramer, John, Kuperman, Samuel, Lucae, Susanne, Lynskey, Michael T, Maier, Wolfgang, Mann, Karl, Männistö, Satu, Müller-Myhsok, Bertram, Murray, Alison D, Nurnberger, John I, Palotie, Aarno, Preuss, Ulrich, Räikkönen, Katri, Reynolds, Maureen D, Ridinger, Monika, Scherbaum, Norbert, Schuckit, Marc A, Soyka, Michael, Treutlein, Jens, Witt, Stephanie, and Wodarz, Norbert

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Alcoholism, Alcohol Use and Health, Neurosciences, Brain Disorders, Substance Misuse, Mental Health, Genetics, Behavioral and Social Science, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Alcoholism, Alleles, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Mental Disorders, Phenotype, Polymorphism, Single Nucleotide, 23andMe Research Team, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10-13) and African ancestries (rs2066702; P = 2.2 × 10-9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.

Published
2018

5. A large-scale genome-wide association study meta-analysis of cannabis use disorder

Author

Walters, Raymond, Polimanti, Renato, Johnson, Emma, McClintick, Jeanette, Hatoum, Alexander, He, June, Wendt, Frank, Zhou, Hang, Adams, Mark, Adkins, Amy, Aliev, Fazil, Bacanu, Silviu-Alin, Batzler, Anthony, Bertelsen, Sarah, Biernacka, Joanna, Bigdeli, Tim, Chen, Li-Shiun, Clarke, Toni-Kim, Chou, Yi-Ling, Degenhardt, Franziska, Docherty, Anna, Edwards, Alexis, Fontanillas, Pierre, Foo, Jerome, Fox, Louis, Frank, Josef, Giegling, Ina, Gordon, Scott, Hack, Laura, Hartmann, Annette, Hartz, Sarah, Heilmann-Heimbach, Stefanie, Herms, Stefan, Hodgkinson, Colin, Hoffman, Per, Hottenga, Jouke, Kennedy, Martin, Alanne-Kinnunen, Mervi, Konte, Bettina, Lahti, Jari, Lahti-Pulkkinen, Marius, Lai, Dongbing, Ligthart, Lannie, Loukola, Anu, Maher, Brion, Mbarek, Hamdi, McIntosh, Andrew, McQueen, Matthew, Meyers, Jacquelyn, Milaneschi, Yuri, Palviainen, Teemu, Pearson, John, Peterson, Roseann, Ripatti, Samuli, Ryu, Euijung, Saccone, Nancy, Salvatore, Jessica, Sanchez-Roige, Sandra, Schwandt, Melanie, Sherva, Richard, Streit, Fabian, Strohmaier, Jana, Thomas, Nathaniel, Wang, Jen-Chyong, Webb, Bradley, Wedow, Robbee, Wetherill, Leah, Wills, Amanda, Boardman, Jason, Chen, Danfeng, Choi, Doo-Sup, Copeland, William, Culverhouse, Robert, Dahmen, Norbert, Degenhardt, Louisa, Domingue, Benjamin, Elson, Sarah, Frye, Mark, Gäbel, Wolfgang, Hayward, Caroline, Ising, Marcus, Keyes, Margaret, Kiefer, Falk, Kramer, John, Kuperman, Samuel, Lucae, Susanne, Lynskey, Michael, Maier, Wolfgang, Mann, Karl, Männistö, Satu, Müller-Myhsok, Bertram, Murray, Alison, Nurnberger, John, Palotie, Aarno, Preuss, Ulrich, Räikkönen, Katri, Reynolds, Maureen, Ridinger, Monika, Scherbaum, Norbert, Schuckit, Marc, Soyka, Michael, Treutlein, Jens, Witt, Stephanie, Wodarz, Norbert, Zill, Peter, Adkins, Daniel, Boden, Joseph, Boomsma, Dorret, Bierut, Laura, Brown, Sandra, Bucholz, Kathleen, Cichon, Sven, Costello, E. Jane, de Wit, Harriet, Diazgranados, Nancy, Dick, Danielle, Eriksson, Johan, Farrer, Lindsay, Foroud, Tatiana, Gillespie, Nathan, Goate, Alison, Goldman, David, Grucza, Richard, Hancock, Dana, Harris, Kathleen Mullan, Heath, Andrew, Hesselbrock, Victor, Hewitt, John, Hopfer, Christian, Horwood, John, Iacono, William, Johnson, Eric, Kaprio, Jaakko, Karpyak, Victor, Kendler, Kenneth, Kranzler, Henry, Krauter, Kenneth, Lichtenstein, Paul, Lind, Penelope, McGue, Matt, MacKillop, James, Madden, Pamela, Maes, Hermine, Magnusson, Patrik, Martin, Nicholas, Medland, Sarah, Montgomery, Grant, Nelson, Elliot, Nöthen, Markus, Palmer, Abraham, Pederson, Nancy, Penninx, Brenda, Porjesz, Bernice, Rice, John, Rietschel, Marcella, Riley, Brien, Rose, Richard, Rujescu, Dan, Shen, Pei-Hong, Silberg, Judy, Stallings, Michael, Tarter, Ralph, Vanyukov, Michael, Vrieze, Scott, Wall, Tamara, Whitfield, John, Zhao, Hongyu, Neale, Benjamin, Gelernter, Joel, Edenberg, Howard, Agrawal, Arpana, Johnson, Emma C, Demontis, Ditte, Thorgeirsson, Thorgeir E, Walters, Raymond K, Hatoum, Alexander S, Paul, Sarah E, Wendt, Frank R, Reginsson, Gunnar W, Baranger, David A A, Gudbjartsson, Daniel F, Adkins, Daniel E, Adkins, Amy E, Alexander, Jeffry, Bigdeli, Tim B, Brown, Sandra A, Bucholz, Kathleen K, Bybjerg-Grauholm, Jonas, Corley, Robin P, Dick, Danielle M, Domingue, Benjamin W, Goate, Alison M, Gordon, Scott D, Hack, Laura M, Hancock, Dana B, Hartz, Sarah M, Hickie, Ian B, Hougaard, David M, Lind, Penelope A, McClintick, Jeanette N, McQueen, Matthew B, Meyers, Jacquelyn L, Montgomery, Grant W, Mors, Ole, Mortensen, Preben B, Nordentoft, Merete, Pearson, John F, Peterson, Roseann E, Reynolds, Maureen D, Rice, John P, Runarsdottir, Valgerdur, Saccone, Nancy L, Silberg, Judy L, Tarter, Ralph E, Tyrfingsson, Thorarinn, Wall, Tamara L, Webb, Bradley T, Werge, Thomas, Wright, Margaret J, Zellers, Stephanie, Adams, Mark J, Bierut, Laura J, Boardman, Jason D, Copeland, William E, Farrer, Lindsay A, Foroud, Tatiana M, Gillespie, Nathan A, Grucza, Richard A, Heath, Andrew C, Hewitt, John K, Hopfer, Christian J, Iacono, William G, Johnson, Eric O, Kendler, Kenneth S, Kennedy, Martin A, Kranzler, Henry R, Madden, Pamela A F, Maes, Hermine H, Maher, Brion S, Martin, Nicholas G, McGue, Matthew, McIntosh, Andrew M, Medland, Sarah E, Nelson, Elliot C, Riley, Brien P, Stallings, Michael C, Vanyukov, Michael M, Davis, Lea K, Bogdan, Ryan, Edenberg, Howard J, Stefansson, Kari, and Børglum, Anders D

Published
2020
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7. Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use

Author

Surendran, Praveen, Young, Robin, Barnes, Daniel R., Nielsen, Sune Fallgaard, Rasheed, Asif, Samuel, Maria, Zhao, Wei, Kontto, Jukka, Perola, Markus, Caslake, Muriel, de Craen, Anton J.M., Trompet, Stella, Uria-Nickelsen, Maria, Malarstig, Anders, Reily, Dermot F., Hoek, Maarten, Vogt, Thomas, Jukema, J. Wouter, Sattar, Naveed, Ford, Ian, Packard, Chris J., Alam, Dewan S., Majumder, Abdulla al Shafi, Di Angelantonio, Emanuele, Chowdhury, Rajiv, Amouyel, Philippe, Arveiler, Dominique, Blankenberg, Stefan, Ferrières, Jean, Kee, Frank, Kuulasmaa, Kari, Müller-Nurasyid, Martina, Veronesi, Giovanni, Virtamo, Jarmo, EPIC-CVD Consortium, Frossard, Philippe, Nordestgaard, Børge Grønne, Saleheen, Danish, Danesh, John, Butterworth, Adam S., Howson, Joanna M.M., Erzurumluoglu, A. Mesut, Jackson, Victoria E., Melbourne, Carl A., Varga, Tibor V., Warren, Helen R., Tragante, Vinicius, Tachmazidou, Ioanna, Harris, Sarah E., Evangelou, Evangelos, Marten, Jonathan, Zhang, Weihua, Altmaier, Elisabeth, Luan, Jian’an, Langenberg, Claudia, Scott, Robert A., Yaghootkar, Hanieh, Stirrups, Kathleen, Kanoni, Stavroula, Marouli, Eirini, Karpe, Fredrik, Dominiczak, Anna F., Sever, Peter, Poulter, Neil, Rolandsson, Olov, Baumbach, Clemens, Afaq, Saima, Chambers, John C., Kooner, Jaspal S., Wareham, Nicholas J., Renström, Frida, Hallmans, Göran, Marioni, Riccardo E., Corley, Janie, Starr, John M., Verweij, Niek, de Boer, Rudolf A., van der Meer, Peter, Yavas, Ersin, Vaartjes, Ilonca, Bots, Michiel L., Asselbergs, Folkert W., Grabe, Hans J., Völzke, Henry, Nauck, Matthias, Weiss, Stefan, Pharoah, Paul D.P., Dunning, Alison M., Dennis, Joe G., Thompson, Deborah J., Michailidou, Kyriaki, Easton, Douglas F., Antoniou, Antonis C., Tyrrell, Jessica, Mihailov, Evelin, Samani, Nilesh J., Zhou, Kaixin, Neville, Matthew J., Metspalu, Andres, Palmer, Colin N.A., Hall, Ian P., Strachan, David P., Deary, Ian J., Frayling, Tim M., Hayward, Caroline, van der Harst, Pim, Zeggini, Eleftheria, Understanding Society Scientific Group, Munroe, Patricia B., Jansson, Jan-Håkan, Franks, Paul W., Deloukas, Panos, Caulfield, Mark J., Wain, Louise V., Tobin, Martin D., Brazel, David M., Jiang, Yu, Hughey, Jordan M., Turcot, Valérie, Zhan, Xiaowei, Gong, Jian, Batini, Chiara, Weissenkampen, J. Dylan, Liu, MengZhen, Bertelsen, Sarah, Chou, Yi-Ling, Faul, Jessica D., Haessler, Jeff, Hammerschlag, Anke R., Hsu, Chris, Kapoor, Manav, Lai, Dongbing, Le, Nhung, de Leeuw, Christiaan A., Loukola, Anu, Mangino, Massimo, Pistis, Giorgio, Qaiser, Beenish, Rohde, Rebecca, Shao, Yaming, Stringham, Heather, Wetherill, Leah, Agrawal, Arpana, Bierut, Laura, Chen, Chu, Eaton, Charles B., Goate, Alison, Haiman, Christopher, Heath, Andrew, Iacono, William G., Martin, Nicholas G., Polderman, Tinca J., Reiner, Alex, Rice, John, Schlessinger, David, Scholte, H. Steven, Smith, Jennifer A., Tardif, Jean-Claude, Tindle, Hilary A., van der Leij, Andries R., Boehnke, Michael, Chang-Claude, Jenny, Cucca, Francesco, David, Sean P., Foroud, Tatiana, Kardia, Sharon L.R., Kooperberg, Charles, Laakso, Markku, Lettre, Guillaume, Madden, Pamela, McGue, Matt, North, Kari, Posthuma, Danielle, Spector, Timothy, Stram, Daniel, Weir, David R., Kaprio, Jaakko, Abecasis, Gonçalo R., Liu, Dajiang J., and Vrieze, Scott

Published
2019
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10. A systematic approach to reduce intraocular pressure for the treatment of glaucoma

Author

Huang, Yi‐Lun, primary, Hsu, Yu‐Ling, additional, Yu, Ya‐Chu, additional, Huang, Hong‐Yan, additional, Tsai, Ren‐Hao, additional, Cheng, Yao‐Tien, additional, Chou, Yi‐Ling, additional, Sun, Sheng‐Yan, additional, Wang, Li‐An, additional, Lin, Jia‐Yi, additional, Chen, Chao‐Chung, additional, Hung, Jia‐Horung, additional, and Ng, I‐Son, additional

Published
2022
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12. A Quantitative-Trait Genome-Wide Association Study of Alcoholism Risk in the Community: Findings and Implications

Author

Heath, Andrew C., Whitfield, John B., Martin, Nicholas G., Pergadia, Michele L., Goate, Alison M., Lind, Penelope A., McEvoy, Brian P., Schrage, Andrew J., Grant, Julia D., Chou, Yi-Ling, Zhu, Rachel, Henders, Anjali K., Medland, Sarah E., Gordon, Scott D., Nelson, Elliot C., Agrawal, Arpana, Nyholt, Dale R., Bucholz, Kathleen K., Madden, Pamela A.F., and Montgomery, Grant W.

Published
2011
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13. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author

Munn-Chernoff, Melissa A, Johnson, Emma C, Chou, Yi-Ling, Coleman, Jonathan RI, Thornton, Laura M, Walters, Raymond K, Yilmaz, Zeynep, Baker, Jessica H, Hübel, Christopher, Gordon, Scott, Medland, Sarah E, Watson, Hunna J, Gaspar, Héléna A, Bryois, Julien, Hinney, Anke, Leppä, Virpi M, Mattheisen, Manuel, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Hanscombe, Ken B, Adan, Roger AH, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A, Berrettini, Wade H, Boehm, Ilka, Boni, Claudette, Boraska Perica, Vesna, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D, Courtet, Philippe, Crow, Scott, Crowley, James J, Danner, Unna N, Davis, Oliver SP, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E, Dick, Danielle M, Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E, Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M, Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas J, Forzan, Monica, Franklin, Christopher S, Gallinger, Steven, Giegling, Ina, Giuranna, Johanna, Gonidakis, Fragiskos, Gorwood, Philip, Gratacos Mayora, Monica, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske G, Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Huckins, Laura M, Hudson, James I, Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Karhunen, Leila, Karwautz, Andreas, Kas, Martien JH, Kennedy, James L, Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Klump, Kelly L, Knudsen, Gun Peggy S, and La Via, Maria C

Subjects
Drug Abuse (NIDA Only), Substance-Related Disorders, Eating Disorders, substance use, Medical and Health Sciences, Linkage Disequilibrium, Feeding and Eating Disorders, Substance Misuse, Alcohol Use and Health, Risk Factors, Clinical Research, 2.3 Psychological, mental disorders, Tobacco, Genetics, Humans, 2.1 Biological and endogenous factors, Aetiology, Polymorphism, Nutrition, Depressive Disorder, Tobacco Smoke and Health, Prevention, Human Genome, Psychology and Cognitive Sciences, Substance Abuse, Major, Tobacco Use Disorder, Single Nucleotide, genetic correlation, Brain Disorders, Alcoholism, Good Health and Well Being, Phenotype, Mental Health, Schizophrenia, social and economic factors, Genome-Wide Association Study
Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.

Published
2021

14. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Author

Erzurumluoglu, A Mesut, Liu, Mengzhen, Jackson, Victoria E, Barnes, Daniel R, Datta, Gargi, Melbourne, Carl A, Young, Robin, Batini, Chiara, Surendran, Praveen, Jiang, Tao, Adnan, Sheikh Daud, Afaq, Saima, Agrawal, Arpana, Altmaier, Elisabeth, Antoniou, Antonis C, Asselbergs, Folkert W, Baumbach, Clemens, Bierut, Laura, Bertelsen, Sarah, Boehnke, Michael, Bots, Michiel L, Brazel, David M, Chambers, John C, Chang-Claude, Jenny, Chen, Chu, Corley, Janie, Chou, Yi-Ling, David, Sean P, de Boer, Rudolf A, de Leeuw, Christiaan A, Dennis, Joe G, Dominiczak, Anna F, Dunning, Alison M, Easton, Douglas F, Eaton, Charles, Elliott, Paul, Evangelou, Evangelos, Faul, Jessica D, Foroud, Tatiana, Goate, Alison, Gong, Jian, Grabe, Hans J, Haessler, Jeff, Haiman, Christopher, Hallmans, Göran, Karpe, Fredrik, Nielsen, Sune Fallgaard, Varga, Tibor V, Chen, Fang, Nordestgaard, Børge Grønne, Cardiovascular Centre (CVC), and Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)

Subjects
RISK, LUNG-CANCER, DATABASE, LD SCORE REGRESSION, BIOLOGICAL INSIGHTS, MENDELIAN RANDOMIZATION, EFFICIENT, CIGARETTE-SMOKING, GENOME-WIDE ASSOCIATION, DISEASE
Abstract

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P

Published
2020

15. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Author

Erzurumluoglu, A. Mesut, Liu, Mengzhen, Jackson, Victoria E., Barnes, Daniel R., Datta, Gargi, Melbourne, Carl A., Young, Robin, Batini, Chiara, Surendran, Praveen, Jiang, Tao, Adnan, Sheikh Daud, Afaq, Saima, Agrawal, Arpana, Altmaier, Elisabeth, Antoniou, Antonis C., Asselbergs, Folkert W., Baumbach, Clemens, Bierut, Laura, Bertelsen, Sarah, Boehnke, Michael, Bots, Michiel L, Brazel, David M, Chambers, John C, Chang-Claude, Jenny, Chen, Chu, Corley, Janie, Chou, Yi-Ling, David, Sean P, de Boer, Rudolf A, de Leeuw, Christiaan A, Dennis, Joe G, Dominiczak, Anna F, Dunning, Alison M, Easton, Douglas F, Eaton, Charles, Elliott, Paul, Evangelou, Evangelos, Faul, Jessica D, Foroud, Tatiana, Goate, Alison, Gong, Jian, Grabe, Hans J, Haessler, Jeff, Haiman, Christopher, Hallmans, Göran, Hammerschlag, Anke R, Harris, Sarah E, Hattersley, Andrew, Heath, Andrew, Hsu, Chris, Iacono, William G, Kanoni, Stavroula, Kapoor, Manav, Kaprio, Jaakko, Kardia, Sharon L, Karpe, Fredrik, Kontto, Jukka, Kooner, Jaspal S, Kooperberg, Charles, Kuulasmaa, Kari, Laakso, Markku, Lai, Dongbing, Langenberg, Claudia, Le, Nhung, Lettre, Guillaume, Loukola, Anu, Luan, Jian'an, Madden, Pamela A F, Mangino, Massimo, Marioni, Riccardo E, Marouli, Eirini, Marten, Jonathan, Martin, Nicholas G, McGue, Matt, Michailidou, Kyriaki, Mihailov, Evelin, Moayyeri, Alireza, Moitry, Marie, Müller-Nurasyid, Martina, Naheed, Aliya, Nauck, Matthias, Neville, Matthew J, Nielsen, Sune Fallgaard, North, Kari, Perola, Markus, Pharoah, Paul D P, Pistis, Giorgio, Polderman, Tinca J, Posthuma, Danielle, Poulter, Neil, Qaiser, Beenish, Rasheed, Asif, Reiner, Alex, Renstrom, Frida, Rice, John, Rohde, Rebecca, Rolandsson, Olov, Samani, Nilesh J, Samuel, Maria, Schlessinger, David, Scholte, Steven H, Scott, Robert A, Sever, Peter, Shao, Yaming, Shrine, Nick, Smith, Jennifer A, Starr, John M, Stirrups, Kathleen, Stram, Danielle, Stringham, Heather M, Tachmazidou, Ioanna, Tardif, Jean-Claude, Thompson, Deborah J, Tindle, Hilary A, Tragante, Vinicius, Trompet, Stella, Turcot, Valerie, Tyrrell, Jessica, Vaartjes, Ilonca, van der Leij, Andries R, van der Meer, Peter, Varga, Tibor V, Verweij, Niek, Völzke, Henry, Wareham, Nicholas J, Warren, Helen R, Weir, David R, Weiss, Stefan, Wetherill, Leah, Yaghootkar, Hanieh, Yavas, Ersin, Jiang, Yu, Chen, Fang, Zhan, Xiaowei, Zhang, Weihua, Zhao, Wei, Zhou, Kaixin, Amouyel, Philippe, Blankenberg, Stefan, Caulfield, Mark J, Chowdhury, Rajiv, Cucca, Francesco, Deary, Ian J, Deloukas, Panos, Di Angelantonio, Emanuele, Ferrario, Marco, Ferrières, Jean, Franks, Paul W, Frayling, Tim M, Frossard, Philippe, Hall, Ian P, Hayward, Caroline, Jansson, Jan-Håkan, Jukema, J Wouter, Kee, Frank, Männistö, Satu, Metspalu, Andres, Munroe, Patricia B, Nordestgaard, Børge Grønne, Palmer, Colin N A, Salomaa, Veikko, Sattar, Naveed, Spector, Timothy, Strachan, David Peter, van der Harst, Pim, Zeggini, Eleftheria, Saleheen, Danish, Butterworth, Adam S, Wain, Louise V, Abecasis, Goncalo R, Danesh, John, Tobin, Martin D, Vrieze, Scott, Liu, Dajiang J, Howson, Joanna M M, Erzurumluoglu, A. Mesut, Liu, Mengzhen, Jackson, Victoria E., Barnes, Daniel R., Datta, Gargi, Melbourne, Carl A., Young, Robin, Batini, Chiara, Surendran, Praveen, Jiang, Tao, Adnan, Sheikh Daud, Afaq, Saima, Agrawal, Arpana, Altmaier, Elisabeth, Antoniou, Antonis C., Asselbergs, Folkert W., Baumbach, Clemens, Bierut, Laura, Bertelsen, Sarah, Boehnke, Michael, Bots, Michiel L, Brazel, David M, Chambers, John C, Chang-Claude, Jenny, Chen, Chu, Corley, Janie, Chou, Yi-Ling, David, Sean P, de Boer, Rudolf A, de Leeuw, Christiaan A, Dennis, Joe G, Dominiczak, Anna F, Dunning, Alison M, Easton, Douglas F, Eaton, Charles, Elliott, Paul, Evangelou, Evangelos, Faul, Jessica D, Foroud, Tatiana, Goate, Alison, Gong, Jian, Grabe, Hans J, Haessler, Jeff, Haiman, Christopher, Hallmans, Göran, Hammerschlag, Anke R, Harris, Sarah E, Hattersley, Andrew, Heath, Andrew, Hsu, Chris, Iacono, William G, Kanoni, Stavroula, Kapoor, Manav, Kaprio, Jaakko, Kardia, Sharon L, Karpe, Fredrik, Kontto, Jukka, Kooner, Jaspal S, Kooperberg, Charles, Kuulasmaa, Kari, Laakso, Markku, Lai, Dongbing, Langenberg, Claudia, Le, Nhung, Lettre, Guillaume, Loukola, Anu, Luan, Jian'an, Madden, Pamela A F, Mangino, Massimo, Marioni, Riccardo E, Marouli, Eirini, Marten, Jonathan, Martin, Nicholas G, McGue, Matt, Michailidou, Kyriaki, Mihailov, Evelin, Moayyeri, Alireza, Moitry, Marie, Müller-Nurasyid, Martina, Naheed, Aliya, Nauck, Matthias, Neville, Matthew J, Nielsen, Sune Fallgaard, North, Kari, Perola, Markus, Pharoah, Paul D P, Pistis, Giorgio, Polderman, Tinca J, Posthuma, Danielle, Poulter, Neil, Qaiser, Beenish, Rasheed, Asif, Reiner, Alex, Renstrom, Frida, Rice, John, Rohde, Rebecca, Rolandsson, Olov, Samani, Nilesh J, Samuel, Maria, Schlessinger, David, Scholte, Steven H, Scott, Robert A, Sever, Peter, Shao, Yaming, Shrine, Nick, Smith, Jennifer A, Starr, John M, Stirrups, Kathleen, Stram, Danielle, Stringham, Heather M, Tachmazidou, Ioanna, Tardif, Jean-Claude, Thompson, Deborah J, Tindle, Hilary A, Tragante, Vinicius, Trompet, Stella, Turcot, Valerie, Tyrrell, Jessica, Vaartjes, Ilonca, van der Leij, Andries R, van der Meer, Peter, Varga, Tibor V, Verweij, Niek, Völzke, Henry, Wareham, Nicholas J, Warren, Helen R, Weir, David R, Weiss, Stefan, Wetherill, Leah, Yaghootkar, Hanieh, Yavas, Ersin, Jiang, Yu, Chen, Fang, Zhan, Xiaowei, Zhang, Weihua, Zhao, Wei, Zhou, Kaixin, Amouyel, Philippe, Blankenberg, Stefan, Caulfield, Mark J, Chowdhury, Rajiv, Cucca, Francesco, Deary, Ian J, Deloukas, Panos, Di Angelantonio, Emanuele, Ferrario, Marco, Ferrières, Jean, Franks, Paul W, Frayling, Tim M, Frossard, Philippe, Hall, Ian P, Hayward, Caroline, Jansson, Jan-Håkan, Jukema, J Wouter, Kee, Frank, Männistö, Satu, Metspalu, Andres, Munroe, Patricia B, Nordestgaard, Børge Grønne, Palmer, Colin N A, Salomaa, Veikko, Sattar, Naveed, Spector, Timothy, Strachan, David Peter, van der Harst, Pim, Zeggini, Eleftheria, Saleheen, Danish, Butterworth, Adam S, Wain, Louise V, Abecasis, Goncalo R, Danesh, John, Tobin, Martin D, Vrieze, Scott, Liu, Dajiang J, and Howson, Joanna M M

Abstract

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

Published
2020
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16. Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

Author

Munn-Chernoff, Melissa A., Johnson, Emma C., Chou, Yi Ling, Coleman, Jonathan R.I., Thornton, Laura M., Walters, Raymond K., Yilmaz, Zeynep, Baker, Jessica H., Hübel, Christopher, Gordon, Scott, Medland, Sarah E., Watson, Hunna J., Gaspar, Héléna A., Bryois, Julien, Hinney, Anke, Leppä, Virpi M., Mattheisen, Manuel, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Hanscombe, Ken B., Adan, Roger A.H., Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A., Berrettini, Wade H., Boehm, Ilka, Boni, Claudette, Boraska Perica, Vesna, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D., Courtet, Philippe, Crow, Scott, Crowley, James J., Danner, Unna N., Davis, Oliver S.P., de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E., Dick, Danielle M., Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E., Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M., Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas J., Forzan, Monica, Franklin, Christopher S., Gallinger, Steven, Giegling, Ina, Giuranna, Johanna, Gonidakis, Fragiskos, Gorwood, Philip, Gratacos Mayora, Monica, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske G., Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Huckins, Laura M., Hudson, James I., Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Karhunen, Leila, Karwautz, Andreas, Kas, Martien J.H., Kennedy, James L., Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl Ri, Klump, Kelly L., Knudsen, Gun Peggy S., La Via, Maria C., Le Hellard, Stephanie, Levitan, Robert D., Li, Dong, Lilenfeld, Lisa, Lin, Bochao Danae, Lissowska, Jolanta, Luykx, Jurjen, Magistretti, Pierre J., Maj, Mario, Mannik, Katrin, Marsal, Sara, Marshall, Christian R., Mattingsdal, Morten, McDevitt, Sara, McGuffin, Peter, Metspalu, Andres, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, Karen, Monteleone, Alessio Maria, Monteleone, Palmiero, Nacmias, Benedetta, Navratilova, Marie, Ntalla, Ioanna, O'Toole, Julie K., Ophoff, Roel A., Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Pinto, Dalila, Rabionet, Raquel, Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rotondo, Alessandro, Rujescu, Dan, Rybakowski, Filip, Santonastaso, Paolo, Scherag, André, Scherer, Stephen W., Schmidt, Ulrike, Schork, Nicholas J., Schosser, Alexandra, Seitz, Jochen, Slachtova, Lenka, Slagboom, P. Eline, Slof-Op't Landt, Margarita C.T., Slopien, Agnieszka, Sorbi, Sandro, Świątkowska, Beata, Szatkiewicz, Jin P., Tachmazidou, Ioanna, Tenconi, Elena, Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie A., van Furth, Eric F., Wagner, Gudrun, Walton, Esther, Widen, Elisabeth, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Bergen, Andrew W., Boden, Joseph M., Brandt, Harry, Crawford, Steven, Halmi, Katherine A., Horwood, L. John, Johnson, Craig, Kaplan, Allan S., Kaye, Walter H., Mitchell, James, Olsen, Catherine M., Pearson, John F., Pedersen, Nancy L., Strober, Michael, Werge, Thomas, Whiteman, David C., Woodside, D. Blake, Grove, Jakob, Henders, Anjali K., Larsen, Janne T., Parker, Richard, Petersen, Liselotte V., Jordan, Jennifer, Kennedy, Martin A., Birgegård, Andreas, Lichtenstein, Paul, Norring, Claes, Landén, Mikael, Mortensen, Preben Bo, Polimanti, Renato, McClintick, Jeanette N., Adkins, Amy E., Aliev, Fazil, Bacanu, Silviu Alin, Batzler, Anthony, Bertelsen, Sarah, Biernacka, Joanna M., Bigdeli, Tim B., Chen, Li Shiun, Clarke, Toni Kim, Degenhardt, Franziska, Docherty, Anna R., Edwards, Alexis C., Foo, Jerome C., Fox, Louis, Frank, Josef, Hack, Laura M., Hartmann, Annette M., Hartz, Sarah M., Heilmann-Heimbach, Stefanie, Hodgkinson, Colin, Hoffmann, Per, Hottenga, Jouke Jan, Konte, Bettina, Lahti, Jari, Lahti-Pulkkinen, Marius, Lai, Dongbing, Ligthart, Lannie, Loukola, Anu, Maher, Brion S., Mbarek, Hamdi, McIntosh, Andrew M., McQueen, Matthew B., Meyers, Jacquelyn L., Milaneschi, Yuri, Palviainen, Teemu, Peterson, Roseann E., Ryu, Euijung, Saccone, Nancy L., Salvatore, Jessica E., Sanchez-Roige, Sandra, Schwandt, Melanie, Sherva, Richard, Streit, Fabian, Strohmaier, Jana, Thomas, Nathaniel, Wang, Jen Chyong, Webb, Bradley T., Wedow, Robbee, Wetherill, Leah, Wills, Amanda G., Zhou, Hang, Boardman, Jason D., Chen, Danfeng, Choi, Doo Sup, Copeland, William E., Culverhouse, Robert C., Dahmen, Norbert, Degenhardt, Louisa, Domingue, Benjamin W., Frye, Mark A., Gäbel, Wolfgang, Hayward, Caroline, Ising, Marcus, Keyes, Margaret, Kiefer, Falk, Koller, Gabriele, Kramer, John, Kuperman, Samuel, Lucae, Susanne, Lynskey, Michael T., Maier, Wolfgang, Mann, Karl, Männistö, Satu, Müller-Myhsok, Bertram, Murray, Alison D., Nurnberger, John I., Preuss, Ulrich, Räikkönen, Katri, Reynolds, Maureen D., Ridinger, Monika, Scherbaum, Norbert, Schuckit, Marc A., Soyka, Michael, Treutlein, Jens, Witt, Stephanie H., Wodarz, Norbert, Zill, Peter, Adkins, Daniel E., Boomsma, Dorret I., Bierut, Laura J., Brown, Sandra A., Bucholz, Kathleen K., Costello, E. Jane, de Wit, Harriet, Diazgranados, Nancy, Eriksson, Johan G., Farrer, Lindsay A., Foroud, Tatiana M., Gillespie, Nathan A., Goate, Alison M., Goldman, David, Grucza, Richard A., Hancock, Dana B., Harris, Kathleen Mullan, Hesselbrock, Victor, Hewitt, John K., Hopfer, Christian J., Iacono, William G., Johnson, Eric O., Karpyak, Victor M., Kendler, Kenneth S., Kranzler, Henry R., Krauter, Kenneth, Lind, Penelope A., McGue, Matt, MacKillop, James, Madden, Pamela A.F., Maes, Hermine H., Magnusson, Patrik K.E., Nelson, Elliot C., Nöthen, Markus M., Palmer, Abraham A., Penninx, Brenda W.J.H., Porjesz, Bernice, Rice, John P., Rietschel, Marcella, Riley, Brien P., Rose, Richard J., Shen, Pei Hong, Silberg, Judy, Stallings, Michael C., Tarter, Ralph E., Vanyukov, Michael M., Vrieze, Scott, Wall, Tamara L., Whitfield, John B., Zhao, Hongyu, Neale, Benjamin M., Wade, Tracey D., Heath, Andrew C., Montgomery, Grant W., Martin, Nicholas G., Sullivan, Patrick F., Kaprio, Jaakko, Breen, Gerome, Gelernter, Joel, Edenberg, Howard J., Bulik, Cynthia M., Agrawal, Arpana, Munn-Chernoff, Melissa A., Johnson, Emma C., Chou, Yi Ling, Coleman, Jonathan R.I., Thornton, Laura M., Walters, Raymond K., Yilmaz, Zeynep, Baker, Jessica H., Hübel, Christopher, Gordon, Scott, Medland, Sarah E., Watson, Hunna J., Gaspar, Héléna A., Bryois, Julien, Hinney, Anke, Leppä, Virpi M., Mattheisen, Manuel, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Hanscombe, Ken B., Adan, Roger A.H., Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A., Berrettini, Wade H., Boehm, Ilka, Boni, Claudette, Boraska Perica, Vesna, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D., Courtet, Philippe, Crow, Scott, Crowley, James J., Danner, Unna N., Davis, Oliver S.P., de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E., Dick, Danielle M., Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E., Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M., Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas J., Forzan, Monica, Franklin, Christopher S., Gallinger, Steven, Giegling, Ina, Giuranna, Johanna, Gonidakis, Fragiskos, Gorwood, Philip, Gratacos Mayora, Monica, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske G., Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Huckins, Laura M., Hudson, James I., Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Karhunen, Leila, Karwautz, Andreas, Kas, Martien J.H., Kennedy, James L., Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl Ri, Klump, Kelly L., Knudsen, Gun Peggy S., La Via, Maria C., Le Hellard, Stephanie, Levitan, Robert D., Li, Dong, Lilenfeld, Lisa, Lin, Bochao Danae, Lissowska, Jolanta, Luykx, Jurjen, Magistretti, Pierre J., Maj, Mario, Mannik, Katrin, Marsal, Sara, Marshall, Christian R., Mattingsdal, Morten, McDevitt, Sara, McGuffin, Peter, Metspalu, Andres, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, Karen, Monteleone, Alessio Maria, Monteleone, Palmiero, Nacmias, Benedetta, Navratilova, Marie, Ntalla, Ioanna, O'Toole, Julie K., Ophoff, Roel A., Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Pinto, Dalila, Rabionet, Raquel, Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rotondo, Alessandro, Rujescu, Dan, Rybakowski, Filip, Santonastaso, Paolo, Scherag, André, Scherer, Stephen W., Schmidt, Ulrike, Schork, Nicholas J., Schosser, Alexandra, Seitz, Jochen, Slachtova, Lenka, Slagboom, P. Eline, Slof-Op't Landt, Margarita C.T., Slopien, Agnieszka, Sorbi, Sandro, Świątkowska, Beata, Szatkiewicz, Jin P., Tachmazidou, Ioanna, Tenconi, Elena, Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie A., van Furth, Eric F., Wagner, Gudrun, Walton, Esther, Widen, Elisabeth, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Bergen, Andrew W., Boden, Joseph M., Brandt, Harry, Crawford, Steven, Halmi, Katherine A., Horwood, L. John, Johnson, Craig, Kaplan, Allan S., Kaye, Walter H., Mitchell, James, Olsen, Catherine M., Pearson, John F., Pedersen, Nancy L., Strober, Michael, Werge, Thomas, Whiteman, David C., Woodside, D. Blake, Grove, Jakob, Henders, Anjali K., Larsen, Janne T., Parker, Richard, Petersen, Liselotte V., Jordan, Jennifer, Kennedy, Martin A., Birgegård, Andreas, Lichtenstein, Paul, Norring, Claes, Landén, Mikael, Mortensen, Preben Bo, Polimanti, Renato, McClintick, Jeanette N., Adkins, Amy E., Aliev, Fazil, Bacanu, Silviu Alin, Batzler, Anthony, Bertelsen, Sarah, Biernacka, Joanna M., Bigdeli, Tim B., Chen, Li Shiun, Clarke, Toni Kim, Degenhardt, Franziska, Docherty, Anna R., Edwards, Alexis C., Foo, Jerome C., Fox, Louis, Frank, Josef, Hack, Laura M., Hartmann, Annette M., Hartz, Sarah M., Heilmann-Heimbach, Stefanie, Hodgkinson, Colin, Hoffmann, Per, Hottenga, Jouke Jan, Konte, Bettina, Lahti, Jari, Lahti-Pulkkinen, Marius, Lai, Dongbing, Ligthart, Lannie, Loukola, Anu, Maher, Brion S., Mbarek, Hamdi, McIntosh, Andrew M., McQueen, Matthew B., Meyers, Jacquelyn L., Milaneschi, Yuri, Palviainen, Teemu, Peterson, Roseann E., Ryu, Euijung, Saccone, Nancy L., Salvatore, Jessica E., Sanchez-Roige, Sandra, Schwandt, Melanie, Sherva, Richard, Streit, Fabian, Strohmaier, Jana, Thomas, Nathaniel, Wang, Jen Chyong, Webb, Bradley T., Wedow, Robbee, Wetherill, Leah, Wills, Amanda G., Zhou, Hang, Boardman, Jason D., Chen, Danfeng, Choi, Doo Sup, Copeland, William E., Culverhouse, Robert C., Dahmen, Norbert, Degenhardt, Louisa, Domingue, Benjamin W., Frye, Mark A., Gäbel, Wolfgang, Hayward, Caroline, Ising, Marcus, Keyes, Margaret, Kiefer, Falk, Koller, Gabriele, Kramer, John, Kuperman, Samuel, Lucae, Susanne, Lynskey, Michael T., Maier, Wolfgang, Mann, Karl, Männistö, Satu, Müller-Myhsok, Bertram, Murray, Alison D., Nurnberger, John I., Preuss, Ulrich, Räikkönen, Katri, Reynolds, Maureen D., Ridinger, Monika, Scherbaum, Norbert, Schuckit, Marc A., Soyka, Michael, Treutlein, Jens, Witt, Stephanie H., Wodarz, Norbert, Zill, Peter, Adkins, Daniel E., Boomsma, Dorret I., Bierut, Laura J., Brown, Sandra A., Bucholz, Kathleen K., Costello, E. Jane, de Wit, Harriet, Diazgranados, Nancy, Eriksson, Johan G., Farrer, Lindsay A., Foroud, Tatiana M., Gillespie, Nathan A., Goate, Alison M., Goldman, David, Grucza, Richard A., Hancock, Dana B., Harris, Kathleen Mullan, Hesselbrock, Victor, Hewitt, John K., Hopfer, Christian J., Iacono, William G., Johnson, Eric O., Karpyak, Victor M., Kendler, Kenneth S., Kranzler, Henry R., Krauter, Kenneth, Lind, Penelope A., McGue, Matt, MacKillop, James, Madden, Pamela A.F., Maes, Hermine H., Magnusson, Patrik K.E., Nelson, Elliot C., Nöthen, Markus M., Palmer, Abraham A., Penninx, Brenda W.J.H., Porjesz, Bernice, Rice, John P., Rietschel, Marcella, Riley, Brien P., Rose, Richard J., Shen, Pei Hong, Silberg, Judy, Stallings, Michael C., Tarter, Ralph E., Vanyukov, Michael M., Vrieze, Scott, Wall, Tamara L., Whitfield, John B., Zhao, Hongyu, Neale, Benjamin M., Wade, Tracey D., Heath, Andrew C., Montgomery, Grant W., Martin, Nicholas G., Sullivan, Patrick F., Kaprio, Jaakko, Breen, Gerome, Gelernter, Joel, Edenberg, Howard J., Bulik, Cynthia M., and Agrawal, Arpana

Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotyp

Published
2020

18. A large-scale genome-wide association study meta-analysis of cannabis use disorder

Author

Johnson, Emma C, primary, Demontis, Ditte, additional, Thorgeirsson, Thorgeir E, additional, Walters, Raymond K, additional, Polimanti, Renato, additional, Hatoum, Alexander S, additional, Sanchez-Roige, Sandra, additional, Paul, Sarah E, additional, Wendt, Frank R, additional, Clarke, Toni-Kim, additional, Lai, Dongbing, additional, Reginsson, Gunnar W, additional, Zhou, Hang, additional, He, June, additional, Baranger, David A A, additional, Gudbjartsson, Daniel F, additional, Wedow, Robbee, additional, Adkins, Daniel E, additional, Adkins, Amy E, additional, Alexander, Jeffry, additional, Bacanu, Silviu-Alin, additional, Bigdeli, Tim B, additional, Boden, Joseph, additional, Brown, Sandra A, additional, Bucholz, Kathleen K, additional, Bybjerg-Grauholm, Jonas, additional, Corley, Robin P, additional, Degenhardt, Louisa, additional, Dick, Danielle M, additional, Domingue, Benjamin W, additional, Fox, Louis, additional, Goate, Alison M, additional, Gordon, Scott D, additional, Hack, Laura M, additional, Hancock, Dana B, additional, Hartz, Sarah M, additional, Hickie, Ian B, additional, Hougaard, David M, additional, Krauter, Kenneth, additional, Lind, Penelope A, additional, McClintick, Jeanette N, additional, McQueen, Matthew B, additional, Meyers, Jacquelyn L, additional, Montgomery, Grant W, additional, Mors, Ole, additional, Mortensen, Preben B, additional, Nordentoft, Merete, additional, Pearson, John F, additional, Peterson, Roseann E, additional, Reynolds, Maureen D, additional, Rice, John P, additional, Runarsdottir, Valgerdur, additional, Saccone, Nancy L, additional, Sherva, Richard, additional, Silberg, Judy L, additional, Tarter, Ralph E, additional, Tyrfingsson, Thorarinn, additional, Wall, Tamara L, additional, Webb, Bradley T, additional, Werge, Thomas, additional, Wetherill, Leah, additional, Wright, Margaret J, additional, Zellers, Stephanie, additional, Adams, Mark J, additional, Bierut, Laura J, additional, Boardman, Jason D, additional, Copeland, William E, additional, Farrer, Lindsay A, additional, Foroud, Tatiana M, additional, Gillespie, Nathan A, additional, Grucza, Richard A, additional, Harris, Kathleen Mullan, additional, Heath, Andrew C, additional, Hesselbrock, Victor, additional, Hewitt, John K, additional, Hopfer, Christian J, additional, Horwood, John, additional, Iacono, William G, additional, Johnson, Eric O, additional, Kendler, Kenneth S, additional, Kennedy, Martin A, additional, Kranzler, Henry R, additional, Madden, Pamela A F, additional, Maes, Hermine H, additional, Maher, Brion S, additional, Martin, Nicholas G, additional, McGue, Matthew, additional, McIntosh, Andrew M, additional, Medland, Sarah E, additional, Nelson, Elliot C, additional, Porjesz, Bernice, additional, Riley, Brien P, additional, Stallings, Michael C, additional, Vanyukov, Michael M, additional, Vrieze, Scott, additional, Davis, Lea K, additional, Bogdan, Ryan, additional, Gelernter, Joel, additional, Edenberg, Howard J, additional, Stefansson, Kari, additional, Børglum, Anders D, additional, Agrawal, Arpana, additional, Walters, Raymond, additional, Johnson, Emma, additional, McClintick, Jeanette, additional, Hatoum, Alexander, additional, Wendt, Frank, additional, Adams, Mark, additional, Adkins, Amy, additional, Aliev, Fazil, additional, Batzler, Anthony, additional, Bertelsen, Sarah, additional, Biernacka, Joanna, additional, Bigdeli, Tim, additional, Chen, Li-Shiun, additional, Chou, Yi-Ling, additional, Degenhardt, Franziska, additional, Docherty, Anna, additional, Edwards, Alexis, additional, Fontanillas, Pierre, additional, Foo, Jerome, additional, Frank, Josef, additional, Giegling, Ina, additional, Gordon, Scott, additional, Hack, Laura, additional, Hartmann, Annette, additional, Hartz, Sarah, additional, Heilmann-Heimbach, Stefanie, additional, Herms, Stefan, additional, Hodgkinson, Colin, additional, Hoffman, Per, additional, Hottenga, Jouke, additional, Kennedy, Martin, additional, Alanne-Kinnunen, Mervi, additional, Konte, Bettina, additional, Lahti, Jari, additional, Lahti-Pulkkinen, Marius, additional, Ligthart, Lannie, additional, Loukola, Anu, additional, Maher, Brion, additional, Mbarek, Hamdi, additional, McIntosh, Andrew, additional, McQueen, Matthew, additional, Meyers, Jacquelyn, additional, Milaneschi, Yuri, additional, Palviainen, Teemu, additional, Pearson, John, additional, Peterson, Roseann, additional, Ripatti, Samuli, additional, Ryu, Euijung, additional, Saccone, Nancy, additional, Salvatore, Jessica, additional, Schwandt, Melanie, additional, Streit, Fabian, additional, Strohmaier, Jana, additional, Thomas, Nathaniel, additional, Wang, Jen-Chyong, additional, Webb, Bradley, additional, Wills, Amanda, additional, Boardman, Jason, additional, Chen, Danfeng, additional, Choi, Doo-Sup, additional, Copeland, William, additional, Culverhouse, Robert, additional, Dahmen, Norbert, additional, Domingue, Benjamin, additional, Elson, Sarah, additional, Frye, Mark, additional, Gäbel, Wolfgang, additional, Hayward, Caroline, additional, Ising, Marcus, additional, Keyes, Margaret, additional, Kiefer, Falk, additional, Kramer, John, additional, Kuperman, Samuel, additional, Lucae, Susanne, additional, Lynskey, Michael, additional, Maier, Wolfgang, additional, Mann, Karl, additional, Männistö, Satu, additional, Müller-Myhsok, Bertram, additional, Murray, Alison, additional, Nurnberger, John, additional, Palotie, Aarno, additional, Preuss, Ulrich, additional, Räikkönen, Katri, additional, Reynolds, Maureen, additional, Ridinger, Monika, additional, Scherbaum, Norbert, additional, Schuckit, Marc, additional, Soyka, Michael, additional, Treutlein, Jens, additional, Witt, Stephanie, additional, Wodarz, Norbert, additional, Zill, Peter, additional, Adkins, Daniel, additional, Boomsma, Dorret, additional, Bierut, Laura, additional, Brown, Sandra, additional, Bucholz, Kathleen, additional, Cichon, Sven, additional, Costello, E. Jane, additional, de Wit, Harriet, additional, Diazgranados, Nancy, additional, Dick, Danielle, additional, Eriksson, Johan, additional, Farrer, Lindsay, additional, Foroud, Tatiana, additional, Gillespie, Nathan, additional, Goate, Alison, additional, Goldman, David, additional, Grucza, Richard, additional, Hancock, Dana, additional, Heath, Andrew, additional, Hewitt, John, additional, Hopfer, Christian, additional, Iacono, William, additional, Johnson, Eric, additional, Kaprio, Jaakko, additional, Karpyak, Victor, additional, Kendler, Kenneth, additional, Kranzler, Henry, additional, Lichtenstein, Paul, additional, Lind, Penelope, additional, McGue, Matt, additional, MacKillop, James, additional, Madden, Pamela, additional, Maes, Hermine, additional, Magnusson, Patrik, additional, Martin, Nicholas, additional, Medland, Sarah, additional, Montgomery, Grant, additional, Nelson, Elliot, additional, Nöthen, Markus, additional, Palmer, Abraham, additional, Pederson, Nancy, additional, Penninx, Brenda, additional, Rice, John, additional, Rietschel, Marcella, additional, Riley, Brien, additional, Rose, Richard, additional, Rujescu, Dan, additional, Shen, Pei-Hong, additional, Silberg, Judy, additional, Stallings, Michael, additional, Tarter, Ralph, additional, Vanyukov, Michael, additional, Wall, Tamara, additional, Whitfield, John, additional, Zhao, Hongyu, additional, Neale, Benjamin, additional, and Edenberg, Howard, additional

Published
2020
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19. Shared genetic risk between eating disorder‐ and substance‐use‐related phenotypes: Evidence from genome‐wide association studies

Author

Munn‐Chernoff, Melissa A., primary, Johnson, Emma C., additional, Chou, Yi‐Ling, additional, Coleman, Jonathan R.I., additional, Thornton, Laura M., additional, Walters, Raymond K., additional, Yilmaz, Zeynep, additional, Baker, Jessica H., additional, Hübel, Christopher, additional, Gordon, Scott, additional, Medland, Sarah E., additional, Watson, Hunna J., additional, Gaspar, Héléna A., additional, Bryois, Julien, additional, Hinney, Anke, additional, Leppä, Virpi M., additional, Mattheisen, Manuel, additional, Ripke, Stephan, additional, Yao, Shuyang, additional, Giusti‐Rodríguez, Paola, additional, Hanscombe, Ken B., additional, Adan, Roger A.H., additional, Alfredsson, Lars, additional, Ando, Tetsuya, additional, Andreassen, Ole A., additional, Berrettini, Wade H., additional, Boehm, Ilka, additional, Boni, Claudette, additional, Boraska Perica, Vesna, additional, Buehren, Katharina, additional, Burghardt, Roland, additional, Cassina, Matteo, additional, Cichon, Sven, additional, Clementi, Maurizio, additional, Cone, Roger D., additional, Courtet, Philippe, additional, Crow, Scott, additional, Crowley, James J., additional, Danner, Unna N., additional, Davis, Oliver S.P., additional, de Zwaan, Martina, additional, Dedoussis, George, additional, Degortes, Daniela, additional, DeSocio, Janiece E., additional, Dick, Danielle M., additional, Dikeos, Dimitris, additional, Dina, Christian, additional, Dmitrzak‐Weglarz, Monika, additional, Docampo, Elisa, additional, Duncan, Laramie E., additional, Egberts, Karin, additional, Ehrlich, Stefan, additional, Escaramís, Geòrgia, additional, Esko, Tõnu, additional, Estivill, Xavier, additional, Farmer, Anne, additional, Favaro, Angela, additional, Fernández‐Aranda, Fernando, additional, Fichter, Manfred M., additional, Fischer, Krista, additional, Föcker, Manuel, additional, Foretova, Lenka, additional, Forstner, Andreas J., additional, Forzan, Monica, additional, Franklin, Christopher S., additional, Gallinger, Steven, additional, Giegling, Ina, additional, Giuranna, Johanna, additional, Gonidakis, Fragiskos, additional, Gorwood, Philip, additional, Gratacos Mayora, Monica, additional, Guillaume, Sébastien, additional, Guo, Yiran, additional, Hakonarson, Hakon, additional, Hatzikotoulas, Konstantinos, additional, Hauser, Joanna, additional, Hebebrand, Johannes, additional, Helder, Sietske G., additional, Herms, Stefan, additional, Herpertz‐Dahlmann, Beate, additional, Herzog, Wolfgang, additional, Huckins, Laura M., additional, Hudson, James I., additional, Imgart, Hartmut, additional, Inoko, Hidetoshi, additional, Janout, Vladimir, additional, Jiménez‐Murcia, Susana, additional, Julià, Antonio, additional, Kalsi, Gursharan, additional, Kaminská, Deborah, additional, Karhunen, Leila, additional, Karwautz, Andreas, additional, Kas, Martien J.H., additional, Kennedy, James L., additional, Keski‐Rahkonen, Anna, additional, Kiezebrink, Kirsty, additional, Kim, Youl‐Ri, additional, Klump, Kelly L., additional, Knudsen, Gun Peggy S., additional, La Via, Maria C., additional, Le Hellard, Stephanie, additional, Levitan, Robert D., additional, Li, Dong, additional, Lilenfeld, Lisa, additional, Lin, Bochao Danae, additional, Lissowska, Jolanta, additional, Luykx, Jurjen, additional, Magistretti, Pierre J., additional, Maj, Mario, additional, Mannik, Katrin, additional, Marsal, Sara, additional, Marshall, Christian R., additional, Mattingsdal, Morten, additional, McDevitt, Sara, additional, McGuffin, Peter, additional, Metspalu, Andres, additional, Meulenbelt, Ingrid, additional, Micali, Nadia, additional, Mitchell, Karen, additional, Monteleone, Alessio Maria, additional, Monteleone, Palmiero, additional, Nacmias, Benedetta, additional, Navratilova, Marie, additional, Ntalla, Ioanna, additional, O'Toole, Julie K., additional, Ophoff, Roel A., additional, Padyukov, Leonid, additional, Palotie, Aarno, additional, Pantel, Jacques, additional, Papezova, Hana, additional, Pinto, Dalila, additional, Rabionet, Raquel, additional, Raevuori, Anu, additional, Ramoz, Nicolas, additional, Reichborn‐Kjennerud, Ted, additional, Ricca, Valdo, additional, Ripatti, Samuli, additional, Ritschel, Franziska, additional, Roberts, Marion, additional, Rotondo, Alessandro, additional, Rujescu, Dan, additional, Rybakowski, Filip, additional, Santonastaso, Paolo, additional, Scherag, André, additional, Scherer, Stephen W., additional, Schmidt, Ulrike, additional, Schork, Nicholas J., additional, Schosser, Alexandra, additional, Seitz, Jochen, additional, Slachtova, Lenka, additional, Slagboom, P. Eline, additional, Slof‐Op't Landt, Margarita C.T., additional, Slopien, Agnieszka, additional, Sorbi, Sandro, additional, Świątkowska, Beata, additional, Szatkiewicz, Jin P., additional, Tachmazidou, Ioanna, additional, Tenconi, Elena, additional, Tortorella, Alfonso, additional, Tozzi, Federica, additional, Treasure, Janet, additional, Tsitsika, Artemis, additional, Tyszkiewicz‐Nwafor, Marta, additional, Tziouvas, Konstantinos, additional, van Elburg, Annemarie A., additional, van Furth, Eric F., additional, Wagner, Gudrun, additional, Walton, Esther, additional, Widen, Elisabeth, additional, Zeggini, Eleftheria, additional, Zerwas, Stephanie, additional, Zipfel, Stephan, additional, Bergen, Andrew W., additional, Boden, Joseph M., additional, Brandt, Harry, additional, Crawford, Steven, additional, Halmi, Katherine A., additional, Horwood, L. John, additional, Johnson, Craig, additional, Kaplan, Allan S., additional, Kaye, Walter H., additional, Mitchell, James, additional, Olsen, Catherine M., additional, Pearson, John F., additional, Pedersen, Nancy L., additional, Strober, Michael, additional, Werge, Thomas, additional, Whiteman, David C., additional, Woodside, D. Blake, additional, Grove, Jakob, additional, Henders, Anjali K., additional, Larsen, Janne T., additional, Parker, Richard, additional, Petersen, Liselotte V., additional, Jordan, Jennifer, additional, Kennedy, Martin A., additional, Birgegård, Andreas, additional, Lichtenstein, Paul, additional, Norring, Claes, additional, Landén, Mikael, additional, Mortensen, Preben Bo, additional, Polimanti, Renato, additional, McClintick, Jeanette N., additional, Adkins, Amy E., additional, Aliev, Fazil, additional, Bacanu, Silviu‐Alin, additional, Batzler, Anthony, additional, Bertelsen, Sarah, additional, Biernacka, Joanna M., additional, Bigdeli, Tim B., additional, Chen, Li‐Shiun, additional, Clarke, Toni‐Kim, additional, Degenhardt, Franziska, additional, Docherty, Anna R., additional, Edwards, Alexis C., additional, Foo, Jerome C., additional, Fox, Louis, additional, Frank, Josef, additional, Hack, Laura M., additional, Hartmann, Annette M., additional, Hartz, Sarah M., additional, Heilmann‐Heimbach, Stefanie, additional, Hodgkinson, Colin, additional, Hoffmann, Per, additional, Hottenga, Jouke‐Jan, additional, Konte, Bettina, additional, Lahti, Jari, additional, Lahti‐Pulkkinen, Marius, additional, Lai, Dongbing, additional, Ligthart, Lannie, additional, Loukola, Anu, additional, Maher, Brion S., additional, Mbarek, Hamdi, additional, McIntosh, Andrew M., additional, McQueen, Matthew B., additional, Meyers, Jacquelyn L., additional, Milaneschi, Yuri, additional, Palviainen, Teemu, additional, Peterson, Roseann E., additional, Ryu, Euijung, additional, Saccone, Nancy L., additional, Salvatore, Jessica E., additional, Sanchez‐Roige, Sandra, additional, Schwandt, Melanie, additional, Sherva, Richard, additional, Streit, Fabian, additional, Strohmaier, Jana, additional, Thomas, Nathaniel, additional, Wang, Jen‐Chyong, additional, Webb, Bradley T., additional, Wedow, Robbee, additional, Wetherill, Leah, additional, Wills, Amanda G., additional, Zhou, Hang, additional, Boardman, Jason D., additional, Chen, Danfeng, additional, Choi, Doo‐Sup, additional, Copeland, William E., additional, Culverhouse, Robert C., additional, Dahmen, Norbert, additional, Degenhardt, Louisa, additional, Domingue, Benjamin W., additional, Frye, Mark A., additional, Gäebel, Wolfgang, additional, Hayward, Caroline, additional, Ising, Marcus, additional, Keyes, Margaret, additional, Kiefer, Falk, additional, Koller, Gabriele, additional, Kramer, John, additional, Kuperman, Samuel, additional, Lucae, Susanne, additional, Lynskey, Michael T., additional, Maier, Wolfgang, additional, Mann, Karl, additional, Männistö, Satu, additional, Müller‐Myhsok, Bertram, additional, Murray, Alison D., additional, Nurnberger, John I., additional, Preuss, Ulrich, additional, Räikkönen, Katri, additional, Reynolds, Maureen D., additional, Ridinger, Monika, additional, Scherbaum, Norbert, additional, Schuckit, Marc A., additional, Soyka, Michael, additional, Treutlein, Jens, additional, Witt, Stephanie H., additional, Wodarz, Norbert, additional, Zill, Peter, additional, Adkins, Daniel E., additional, Boomsma, Dorret I., additional, Bierut, Laura J., additional, Brown, Sandra A., additional, Bucholz, Kathleen K., additional, Costello, E. Jane, additional, de Wit, Harriet, additional, Diazgranados, Nancy, additional, Eriksson, Johan G., additional, Farrer, Lindsay A., additional, Foroud, Tatiana M., additional, Gillespie, Nathan A., additional, Goate, Alison M., additional, Goldman, David, additional, Grucza, Richard A., additional, Hancock, Dana B., additional, Harris, Kathleen Mullan, additional, Hesselbrock, Victor, additional, Hewitt, John K., additional, Hopfer, Christian J., additional, Iacono, William G., additional, Johnson, Eric O., additional, Karpyak, Victor M., additional, Kendler, Kenneth S., additional, Kranzler, Henry R., additional, Krauter, Kenneth, additional, Lind, Penelope A., additional, McGue, Matt, additional, MacKillop, James, additional, Madden, Pamela A.F., additional, Maes, Hermine H., additional, Magnusson, Patrik K.E., additional, Nelson, Elliot C., additional, Nöthen, Markus M., additional, Palmer, Abraham A., additional, Penninx, Brenda W.J.H., additional, Porjesz, Bernice, additional, Rice, John P., additional, Rietschel, Marcella, additional, Riley, Brien P., additional, Rose, Richard J., additional, Shen, Pei‐Hong, additional, Silberg, Judy, additional, Stallings, Michael C., additional, Tarter, Ralph E., additional, Vanyukov, Michael M., additional, Vrieze, Scott, additional, Wall, Tamara L., additional, Whitfield, John B., additional, Zhao, Hongyu, additional, Neale, Benjamin M., additional, Wade, Tracey D., additional, Heath, Andrew C., additional, Montgomery, Grant W., additional, Martin, Nicholas G., additional, Sullivan, Patrick F., additional, Kaprio, Jaakko, additional, Breen, Gerome, additional, Gelernter, Joel, additional, Edenberg, Howard J., additional, Bulik, Cynthia M., additional, and Agrawal, Arpana, additional

Published
2020
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20. Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use

Author

Brazel, David M., Jiang, Yu, Hughey, Jordan M., Turcot, Valérie, Zhan, Xiaowei, Gong, Jian, Batini, Chiara, Weissenkampen, J. Dylan, Liu, MengZhen, Barnes, Daniel R., Bertelsen, Sarah, Chou, Yi-Ling, Erzurumluoglu, A. Mesut, Faul, Jessica D., Haessler, Jeff, Hammerschlag, Anke R., Hsu, Chris, Kapoor, Manav, Lai, Dongbing, Le, Nhung, de Leeuw, Christiaan A., Loukola, Anu, Mangino, Massimo, Melbourne, Carl A., Pistis, Giorgio, Qaiser, Beenish, Rohde, Rebecca, Shao, Yaming, Stringham, Heather, Wetherill, Leah, Zhao, Wei, Agrawal, Arpana, Bierut, Laura, Chen, Chu, Eaton, Charles B., Goate, Alison, Haiman, Christopher, Heath, Andrew, Iacono, William G., Martin, Nicholas G., Polderman, Tinca J., Reiner, Alex, Rice, John, Schlessinger, David, Scholte, H. Steven, Smith, Jennifer A., Tardif, Jean-Claude, Tindle, Hilary A., van der Leij, Andries R., Boehnke, Michael, Chang-Claude, Jenny, Cucca, Francesco, David, Sean P., Foroud, Tatiana, Howson, Joanna M. M., Kardia, Sharon L. R., Kooperberg, Charles, Laakso, Markku, Lettre, Guillaume, Madden, Pamela, McGue, Matt, North, Kari, Posthuma, Danielle, Spector, Timothy, Stram, Daniel, Tobin, Martin D., Weir, David R., Kaprio, Jaakko, Abecasis, Gonçalo R., Liu, Dajiang J., Vrieze, Scott, Brazel, David M., Jiang, Yu, Hughey, Jordan M., Turcot, Valérie, Zhan, Xiaowei, Gong, Jian, Batini, Chiara, Weissenkampen, J. Dylan, Liu, MengZhen, Barnes, Daniel R., Bertelsen, Sarah, Chou, Yi-Ling, Erzurumluoglu, A. Mesut, Faul, Jessica D., Haessler, Jeff, Hammerschlag, Anke R., Hsu, Chris, Kapoor, Manav, Lai, Dongbing, Le, Nhung, de Leeuw, Christiaan A., Loukola, Anu, Mangino, Massimo, Melbourne, Carl A., Pistis, Giorgio, Qaiser, Beenish, Rohde, Rebecca, Shao, Yaming, Stringham, Heather, Wetherill, Leah, Zhao, Wei, Agrawal, Arpana, Bierut, Laura, Chen, Chu, Eaton, Charles B., Goate, Alison, Haiman, Christopher, Heath, Andrew, Iacono, William G., Martin, Nicholas G., Polderman, Tinca J., Reiner, Alex, Rice, John, Schlessinger, David, Scholte, H. Steven, Smith, Jennifer A., Tardif, Jean-Claude, Tindle, Hilary A., van der Leij, Andries R., Boehnke, Michael, Chang-Claude, Jenny, Cucca, Francesco, David, Sean P., Foroud, Tatiana, Howson, Joanna M. M., Kardia, Sharon L. R., Kooperberg, Charles, Laakso, Markku, Lettre, Guillaume, Madden, Pamela, McGue, Matt, North, Kari, Posthuma, Danielle, Spector, Timothy, Stram, Daniel, Tobin, Martin D., Weir, David R., Kaprio, Jaakko, Abecasis, Gonçalo R., Liu, Dajiang J., and Vrieze, Scott

Abstract

BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk. METHODS: We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci. RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals. CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior., Group Author(s): CHD Exome Consortium; Consortium Genetics Smoking; EPIC-CVD Consortium; Understanding Soc Sci Grp

Published
2019
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21. Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

Author

Walters, Raymond K., Adams, Mark J., Adkins, Amy E., Aliev, Fazil, Bacanu, Silviu-Alin, Batzler, Anthony, Bertelsen, Sarah, Biernacka, Joanna, Bigdeli, Tim B., Chen, Li-Shiun, Clarke, Toni-Kim, Chou, Yi-Ling, Degenhardt, Franziska, Docherty, Anna R., Fontanillas, Pierre, Foo, Jerome, Fox, Louis, Frank, Josef, Giegling, Ina, Gordon, Scott, Hack, Laura M., Hartmann, Annette M., Hartz, Sarah M., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hodgkinson, Colin, Hoffmann, Per, Hottenga, Jouke-Jan, Kennedy, Martin A., Alanne-Kinnunen, Mervi, Konte, Bettina, Lahti, Jari, Lahti-Pulkkinen, Marius, Ligthart, Lannie, Loukola, Anu-Maria, Maher, Brion S., Mbarek, Hamdi, McIntosh, Andrew M., McQueen, Matthew B., Milaneschi, Yuri, Palviainen, Teemu, Pearson, John F., Peterson, Roseann E., Polimanti, Renato, Ripatti, Samuli, Ryu, Euijung, Saccone, Nancy L., Salvatore, Jessica E., Sanchez-Roige, Sandra, Schwandt, Melanie, Sherva, Richard, Streit, Fabian, Strohmaier, Jana, Thomas, Nathaniel, Wang, Jen-Chyong, Webb, Bradley T., Wedow, Robbee, Wetherill, Leah, Wills, Amanda G., Boardman, Jason D., Chen, Danfeng, Choi, Doo-Sup, Copeland, William E., Culverhouse, Robert C., Dahmen, Norbert, Degenhardt, Louisa, Domingue, Benjamin W., Elson, Sarah L., Frye, Mark, Gäbel, Wolfgang, Ising, Marcus, Johnson, Emma C., Keyes, Margaret, Kiefer, Falk, Kramer, John, Kuperman, Samuel, Lucae, Susanne, Lynskey, Michael T., Maier, Wolfgang, Mann, Karl, Männistö, Satu, McClintick, Jeanette Nance, Meyers, Jacquelyn L., Müller-Myhsok, Bertram, Nurnberger, John I., Palotie, Aarno, Preuss, Ulrich, Räikkönen, Katri, Reynolds, Maureen D., Ridinger, Monika, Scherbaum, Norbert, Shuckit, Marc, Soyka, Michael, Treutlein, Jens, Witt, Stephanie, Wodarz, Norbert, Zill, Peter, Adkins, Daniel E., Boden, Joseph M., Boomsma, Dorret, Bierut, Laura J, Brown, Sandra A., Bucholz, Kathleen K., Cichon, Sven, Costello, E. Jane, de Wit, Harriet, Diazgranados, Nancy, Dick, Danielle M., Eriksson, Johan G., Farrer, Lindsay A., Foroud, Tatiana M., Gillespie, Nathan A., Goate, Alison A., Goldman, David, Grucza, Richard A., Hancock, Dana B., Harris, Kathleen Mullan, Heath, Andrew C., Hesselbrock, Victor, Hewitt, John K., Hopfer, Christian, Horwood, John, Iacono, William, Johnson, Eric O., Kaprio, Jaakko A., Karpyak, Victor, Kendler, Kenneth S., Kranzler, Henry R., Krauter, Kenneth, Lichtenstein, Paul, Lind, Penelope A., McGue, Matt, MacKillop, James, Madden, Pamela A.F., Maes, Hermine, Magnusson, Patrik, Martin, Nicholas G., Medland, Sarah E., Montgomery, Grant W., Nelson, Elliot C., Nöthen, Markus, Palmer, Abraham A., Pedersen, Nancy L., Penninx, Brenda W.J.H., Porjesz, Bernice, Rice, John P., Rietschel, Marcella, Riley, Brien P., Rose, Richard, Rujescu, Dan, Shen, Pei-Hong, Silberg, Judy, Stallings, Michael C., Tarter, Ralph E., Vanyukov, Michael M., Vrieze, Scott, Wall, Tamara L., Whitfield, John B., Zhao, Hongyu, Neale, Benjamin M., Gelernter, Joel, Edenberg, Howard J., and Agrawal, Arpana

Subjects
0303 health sciences, medicine.medical_specialty, biology, Genetic genealogy, Alcohol dependence, ADH1B, Genome-wide association study, biology.organism_classification, medicine.disease, Genetic correlation, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Schizophrenia, medicine, Cannabis, Psychiatry, 030217 neurology & neurosurgery, Depression (differential diagnoses), 030304 developmental biology
Abstract

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest GWAS to date of DSM - IV diagnosed AD. Genome - wide data on 14,904 individuals with AD and 37,944 controls from 28 case / control and family - based studies were meta - analyzed, stratified by genetic ancestry (European, N = 46,568; African; N = 6,280). Independent, genome - wide significant effects of different ADH1B variants were identified in European (rs1229984; p = 9.8E - 13) and African ancestries (rs2066702; p = 2.2E - 9). Significant genetic correlations were observed with schizophrenia, ADHD, depression, and use of cigarettes and cannabis. There was only modest genetic correlation with alcohol consumption and inconsistent associations with problem drinking. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and non - pathological drinking behaviors.

Published
2018
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22. Shared Genetic Risk between Eating Disorder- and Substance-Use-Related Phenotypes: Evidence from Genome-Wide Association Studies

Author

Munn-Chernoff, Melissa A., primary, Johnson, Emma C., additional, Chou, Yi-Ling, additional, Coleman, Jonathan R.I., additional, Thornton, Laura M., additional, Walters, Raymond K., additional, Yilmaz, Zeynep, additional, Baker, Jessica H., additional, Hübel, Christopher, additional, Gordon, Scott, additional, Medland, Sarah E., additional, Watson, Hunna J., additional, Gaspar, Héléna A., additional, Bryois, Julien, additional, Hinney, Anke, additional, Leppä, Virpi M., additional, Mattheisen, Manuel, additional, Ripke, Stephan, additional, Yao, Shuyang, additional, Giusti-Rodríguez, Paola, additional, Hanscombe, Ken B., additional, Adan, Roger A.H., additional, Alfredsson, Lars, additional, Ando, Tetsuya, additional, Andreassen, Ole A., additional, Berrettini, Wade H., additional, Boehm, Ilka, additional, Boni, Claudette, additional, Perica, Vesna Boraska, additional, Buehren, Katharina, additional, Burghardt, Roland, additional, Cassina, Matteo, additional, Cichon, Sven, additional, Clementi, Maurizio, additional, Cone, Roger D., additional, Courtet, Philippe, additional, Crow, Scott, additional, Crowley, James J., additional, Danner, Unna N., additional, Davis, Oliver S.P., additional, Zwaan, Martina de, additional, Dedoussis, George, additional, Degortes, Daniela, additional, DeSocio, Janiece E., additional, Dick, Danielle M., additional, Dikeos, Dimitris, additional, Dina, Christian, additional, Dmitrzak-Weglarz, Monika, additional, Docampo, Elisa, additional, Duncan, Laramie E., additional, Egberts, Karin, additional, Ehrlich, Stefan, additional, Escaramís, Geòrgia, additional, Esko, Tõnu, additional, Estivill, Xavier, additional, Farmer, Anne, additional, Favaro, Angela, additional, Fernández-Aranda, Fernando, additional, Fichter, Manfred M., additional, Fischer, Krista, additional, Föcker, Manuel, additional, Foretova, Lenka, additional, Forstner, Andreas J., additional, Forzan, Monica, additional, Franklin, Christopher S., additional, Gallinger, Steven, additional, Giegling, Ina, additional, Giuranna, Johanna, additional, Gonidakis, Fragiskos, additional, Gorwood, Philip, additional, Mayora, Monica Gratacos, additional, Guillaume, Sébastien, additional, Guo, Yiran, additional, Hakonarson, Hakon, additional, Hatzikotoulas, Konstantinos, additional, Hauser, Joanna, additional, Hebebrand, Johannes, additional, Helder, Sietske G., additional, Herms, Stefan, additional, Herpertz-Dahlmann, Beate, additional, Herzog, Wolfgang, additional, Huckins, Laura M., additional, Hudson, James I., additional, Imgart, Hartmut, additional, Inoko, Hidetoshi, additional, Janout, Vladimir, additional, Jiménez-Murcia, Susana, additional, Julià, Antonio, additional, Kalsi, Gursharan, additional, Kaminská, Deborah, additional, Karhunen, Leila, additional, Karwautz, Andreas, additional, Kas, Martien J.H., additional, Kennedy, James L., additional, Keski-Rahkonen, Anna, additional, Kiezebrink, Kirsty, additional, Kim, Youl-Ri, additional, Klump, Kelly L., additional, Knudsen, Gun Peggy S., additional, Via, Maria C. La, additional, Hellard, Stephanie Le, additional, Levitan, Robert D., additional, Li, Dong, additional, Lilenfeld, Lisa, additional, Lin, Bochao Danae, additional, Lissowska, Jolanta, additional, Luykx, Jurjen, additional, Magistretti, Pierre J., additional, Maj, Mario, additional, Mannik, Katrin, additional, Marsal, Sara, additional, Marshall, Christian R., additional, Mattingsdal, Morten, additional, McDevitt, Sara, additional, McGuffin, Peter, additional, Metspalu, Andres, additional, Meulenbelt, Ingrid, additional, Micali, Nadia, additional, Mitchell, Karen, additional, Monteleone, Alessio Maria, additional, Monteleone, Palmiero, additional, Nacmias, Benedetta, additional, Navratilova, Marie, additional, Ntalla, Ioanna, additional, O’Toole, Julie K., additional, Ophoff, Roel A., additional, Padyukov, Leonid, additional, Palotie, Aarno, additional, Pantel, Jacques, additional, Papezova, Hana, additional, Pinto, Dalila, additional, Rabionet, Raquel, additional, Raevuori, Anu, additional, Ramoz, Nicolas, additional, Reichborn-Kjennerud, Ted, additional, Ricca, Valdo, additional, Ripatti, Samuli, additional, Ritschel, Franziska, additional, Roberts, Marion, additional, Rotondo, Alessandro, additional, Rujescu, Dan, additional, Rybakowski, Filip, additional, Santonastaso, Paolo, additional, Scherag, André, additional, Scherer, Stephen W., additional, Schmidt, Ulrike, additional, Schork, Nicholas J., additional, Schosser, Alexandra, additional, Seitz, Jochen, additional, Slachtova, Lenka, additional, Slagboom, P. Eline, additional, Slof-Op’t Landt, Margarita C.T., additional, Slopien, Agnieszka, additional, Sorbi, Sandro, additional, Świątkowska, Beata, additional, Szatkiewicz, Jin P., additional, Tachmazidou, Ioanna, additional, Tenconi, Elena, additional, Tortorella, Alfonso, additional, Tozzi, Federica, additional, Treasure, Janet, additional, Tsitsika, Artemis, additional, Tyszkiewicz-Nwafor, Marta, additional, Tziouvas, Konstantinos, additional, Elburg, Annemarie A. van, additional, Furth, Eric F. van, additional, Wagner, Gudrun, additional, Walton, Esther, additional, Widen, Elisabeth, additional, Zeggini, Eleftheria, additional, Zerwas, Stephanie, additional, Zipfel, Stephan, additional, Bergen, Andrew W., additional, Boden, Joseph M., additional, Brandt, Harry, additional, Crawford, Steven, additional, Halmi, Katherine A., additional, Horwood, L. John, additional, Johnson, Craig, additional, Kaplan, Allan S., additional, Kaye, Walter H., additional, Mitchell, James, additional, Olsen, Catherine M., additional, Pearson, John F., additional, Pedersen, Nancy L., additional, Strober, Michael, additional, Werge, Thomas, additional, Whiteman, David C., additional, Woodside, D. Blake, additional, Grove, Jakob, additional, Henders, Anjali K., additional, Larsen, Janne T., additional, Parker, Richard, additional, Petersen, Liselotte V., additional, Jordan, Jennifer, additional, Kennedy, Martin A., additional, Birgegård, Andreas, additional, Lichtenstein, Paul, additional, Norring, Claes, additional, Landén, Mikael, additional, Mortensen, Preben Bo, additional, Polimanti, Renato, additional, McClintick, Jeanette N., additional, Adkins, Amy E., additional, Aliev, Fazil, additional, Bacanu, Silviu-Alin, additional, Batzler, Anthony, additional, Bertelsen, Sarah, additional, Biernacka, Joanna M., additional, Bigdeli, Tim B., additional, Chen, Li-Shiun, additional, Clarke, Toni-Kim, additional, Degenhardt, Franziska, additional, Docherty, Anna R., additional, Edwards, Alexis C., additional, Foo, Jerome C., additional, Fox, Louis, additional, Frank, Josef, additional, Hack, Laura M., additional, Hartmann, Annette M., additional, Hartz, Sarah M., additional, Heilmann-Heimbach, Stefanie, additional, Hodgkinson, Colin, additional, Hoffmann, Per, additional, Hottenga, Jouke-Jan, additional, Konte, Bettina, additional, Lahti, Jari, additional, Lahti-Pulkkinen, Marius, additional, Lai, Dongbing, additional, Ligthart, Lannie, additional, Loukola, Anu, additional, Maher, Brion S., additional, Mbarek, Hamdi, additional, McIntosh, Andrew M., additional, McQueen, Matthew B., additional, Meyers, Jacquelyn L., additional, Milaneschi, Yuri, additional, Palviainen, Teemu, additional, Peterson, Roseann E., additional, Ryu, Euijung, additional, Saccone, Nancy L., additional, Salvatore, Jessica E., additional, Sanchez-Roige, Sandra, additional, Schwandt, Melanie, additional, Sherva, Richard, additional, Streit, Fabian, additional, Strohmaier, Jana, additional, Thomas, Nathaniel, additional, Wang, Jen-Chyong, additional, Webb, Bradley T., additional, Wedow, Robbee, additional, Wetherill, Leah, additional, Wills, Amanda G., additional, Zhou, Hang, additional, Boardman, Jason D., additional, Chen, Danfeng, additional, Choi, Doo-Sup, additional, Copeland, William E., additional, Culverhouse, Robert C., additional, Dahmen, Norbert, additional, Degenhardt, Louisa, additional, Domingue, Benjamin W., additional, Frye, Mark A., additional, Gäbel, Wolfgang, additional, Hayward, Caroline, additional, Ising, Marcus, additional, Keyes, Margaret, additional, Kiefer, Falk, additional, Koller, Gabrielle, additional, Kramer, John, additional, Kuperman, Samuel, additional, Lucae, Susanne, additional, Lynskey, Michael T., additional, Maier, Wolfgang, additional, Mann, Karl, additional, Männistö, Satu, additional, Müller-Myhsok, Bertram, additional, Murray, Alison D., additional, Nurnberger, John I., additional, Preuss, Ulrich, additional, Räikkönen, Katri, additional, Reynolds, Maureen D., additional, Ridinger, Monika, additional, Scherbaum, Norbert, additional, Schuckit, Marc A., additional, Soyka, Michael, additional, Treutlein, Jens, additional, Witt, Stephanie H., additional, Wodarz, Norbert, additional, Zill, Peter, additional, Adkins, Daniel E., additional, Boomsma, Dorret I., additional, Bierut, Laura J., additional, Brown, Sandra A., additional, Bucholz, Kathleen K., additional, Costello, E. Jane, additional, Wit, Harriet de, additional, Diazgranados, Nancy, additional, Eriksson, Johan G., additional, Farrer, Lindsay A., additional, Foroud, Tatiana M., additional, Gillespie, Nathan A., additional, Goate, Alison M., additional, Goldman, David, additional, Grucza, Richard A., additional, Hancock, Dana B., additional, Harris, Kathleen Mullan, additional, Hesselbrock, Victor, additional, Hewitt, John K., additional, Hopfer, Christian J., additional, Iacono, William G., additional, Johnson, Eric O., additional, Karpyak, Victor M., additional, Kendler, Kenneth S., additional, Kranzler, Henry R., additional, Krauter, Kenneth, additional, Lind, Penelope A., additional, McGue, Matt, additional, MacKillop, James, additional, Madden, Pamela A.F., additional, Maes, Hermine H., additional, Magnusson, Patrik K.E., additional, Nelson, Elliot C., additional, Nöthen, Markus M., additional, Palmer, Abraham A., additional, Penninx, Brenda W.J.H., additional, Porjesz, Bernice, additional, Rice, John P., additional, Rietschel, Marcella, additional, Riley, Brien P., additional, Rose, Richard J., additional, Shen, Pei-Hong, additional, Silberg, Judy, additional, Stallings, Michael C., additional, Tarter, Ralph E., additional, Vanyukov, Michael M., additional, Vrieze, Scott, additional, Wall, Tamara L., additional, Whitfield, John B., additional, Zhao, Hongyu, additional, Neale, Benjamin M., additional, Wade, Tracey D., additional, Heath, Andrew C., additional, Montgomery, Grant W., additional, Martin, Nicholas G., additional, Sullivan, Patrick F., additional, Kaprio, Jaakko, additional, Breen, Gerome, additional, Gelernter, Joel, additional, Edenberg, Howard J., additional, Bulik, Cynthia M., additional, and Agrawal, Arpana, additional

Published
2019
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28. A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications

Author

Heath, Andrew, Whitfield, John, Martin, Nicholas, Pergadia, Michele, Goate, Alison, Lind, Penelope, McEvoy, Brian, Schrage, Andrew, Grant, Julia, Chou, Yi-Ling, Nyholt, Dale, other, and, Heath, Andrew, Whitfield, John, Martin, Nicholas, Pergadia, Michele, Goate, Alison, Lind, Penelope, McEvoy, Brian, Schrage, Andrew, Grant, Julia, Chou, Yi-Ling, Nyholt, Dale, and other, and

Abstract

BACKGROUND Given moderately strong genetic contributions to variation in alcoholism and heaviness of drinking (50% to 60% heritability) with high correlation of genetic influences, we have conducted a quantitative trait genome-wide association study (GWAS) for phenotypes related to alcohol use and dependence. METHODS Diagnostic interview and blood/buccal samples were obtained from sibships ascertained through the Australian Twin Registry. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed with 8754 individuals (2062 alcohol-dependent cases) selected for informativeness for alcohol use disorder and associated quantitative traits. Family-based association tests were performed for alcohol dependence, dependence factor score, and heaviness of drinking factor score, with confirmatory case-population control comparisons using an unassessed population control series of 3393 Australians with genome-wide SNP data. RESULTS No findings reached genome-wide significance (p = 8.4 x 10(-8) for this study), with lowest p value for primary phenotypes of 1.2 x 10(-7). Convergent findings for quantitative consumption and diagnostic and quantitative dependence measures suggest possible roles for a transmembrane protein gene (TMEM108) and for ANKS1A. The major finding, however, was small effect sizes estimated for individual SNPs, suggesting that hundreds of genetic variants make modest contributions (1/4% of variance or less) to alcohol dependence risk. CONCLUSIONS We conclude that: - 1) meta-analyses of consumption data may contribute usefully to gene discovery; - 2) translation of human alcoholism GWAS results to drug discovery or clinically useful prediction of risk will be challenging, and; - 3) through accumulation across studies, GWAS data may become valuable for improved genetic risk differentiation in research in biological psychiatry (e.g., prospective high-risk or resilience studies).

Published
2011

29. A 3p26-3p25 Genetic Linkage Finding for DSM-IV Major Depression in Heavy Smoking Families

Author

Pergadia, Michele L., primary, Glowinski, Anne L., additional, Wray, Naomi R., additional, Agrawal, Arpana, additional, Saccone, Scott F., additional, Loukola, Anu, additional, Broms, Ulla, additional, Korhonen, Tellervo, additional, Penninx, Brenda W.J.H., additional, Grant, Julia D., additional, Nelson, Elliot C., additional, Henders, Anjali K., additional, Schrage, Andrew J., additional, Chou, Yi-Ling, additional, Keskitalo-Vuokko, Kaisu, additional, Zhu, Qin, additional, Gordon, Scott D., additional, Vink, Jacqueline M., additional, de Geus, Eco J.C., additional, MacGregor, Stuart, additional, Liu, Jimmy Z., additional, Willemsen, Gonneke, additional, Medland, Sarah E., additional, Boomsma, Dorret I., additional, Montgomery, Grant W., additional, Rice, John P., additional, Goate, Alison M., additional, Heath, Andrew C., additional, Kaprio, Jaakko, additional, Martin, Nicholas G., additional, and Madden, Pamela A.F., additional

Published
2011
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30. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Author

Erzurumluoglu, A Mesut, Liu, Mengzhen, Jackson, Victoria E, Barnes, Daniel R, Datta, Gargi, Melbourne, Carl A, Young, Robin, Batini, Chiara, Surendran, Praveen, Jiang, Tao, Adnan, Sheikh Daud, Afaq, Saima, Agrawal, Arpana, Altmaier, Elisabeth, Antoniou, Antonis C, Asselbergs, Folkert W, Baumbach, Clemens, Bierut, Laura, Bertelsen, Sarah, Boehnke, Michael, Bots, Michiel L, Brazel, David M, Chambers, John C, Chang-Claude, Jenny, Chen, Chu, Corley, Janie, Chou, Yi-Ling, David, Sean P, De Boer, Rudolf A, De Leeuw, Christiaan A, Dennis, Joe G, Dominiczak, Anna F, Dunning, Alison M, Easton, Douglas F, Eaton, Charles, Elliott, Paul, Evangelou, Evangelos, Faul, Jessica D, Foroud, Tatiana, Goate, Alison, Gong, Jian, Grabe, Hans J, Haessler, Jeff, Haiman, Christopher, Hallmans, Göran, Hammerschlag, Anke R, Harris, Sarah E, Hattersley, Andrew, Heath, Andrew, Hsu, Chris, Iacono, William G, Kanoni, Stavroula, Kapoor, Manav, Kaprio, Jaakko, Kardia, Sharon L, Karpe, Fredrik, Kontto, Jukka, Kooner, Jaspal S, Kooperberg, Charles, Kuulasmaa, Kari, Laakso, Markku, Lai, Dongbing, Langenberg, Claudia, Le, Nhung, Lettre, Guillaume, Loukola, Anu, Luan, Jian'an, Madden, Pamela AF, Mangino, Massimo, Marioni, Riccardo E, Marouli, Eirini, Marten, Jonathan, Martin, Nicholas G, McGue, Matt, Michailidou, Kyriaki, Mihailov, Evelin, Moayyeri, Alireza, Moitry, Marie, Müller-Nurasyid, Martina, Naheed, Aliya, Nauck, Matthias, Neville, Matthew J, Nielsen, Sune Fallgaard, North, Kari, Perola, Markus, Pharoah, Paul DP, Pistis, Giorgio, Polderman, Tinca J, Posthuma, Danielle, Poulter, Neil, Qaiser, Beenish, Rasheed, Asif, Reiner, Alex, Renström, Frida, Rice, John, Rohde, Rebecca, Rolandsson, Olov, Samani, Nilesh J, Samuel, Maria, Schlessinger, David, Scholte, Steven H, Scott, Robert A, Sever, Peter, Shao, Yaming, Shrine, Nick, Smith, Jennifer A, Starr, John M, Stirrups, Kathleen, Stram, Danielle, Stringham, Heather M, Tachmazidou, Ioanna, Tardif, Jean-Claude, Thompson, Deborah J, Tindle, Hilary A, Tragante, Vinicius, Trompet, Stella, Turcot, Valerie, Tyrrell, Jessica, Vaartjes, Ilonca, Van Der Leij, Andries R, Van Der Meer, Peter, Varga, Tibor V, Verweij, Niek, Völzke, Henry, Wareham, Nicholas J, Warren, Helen R, Weir, David R, Weiss, Stefan, Wetherill, Leah, Yaghootkar, Hanieh, Yavas, Ersin, Jiang, Yu, Chen, Fang, Zhan, Xiaowei, Zhang, Weihua, Zhao, Wei, Zhou, Kaixin, Amouyel, Philippe, Blankenberg, Stefan, Caulfield, Mark J, Chowdhury, Rajiv, Cucca, Francesco, Deary, Ian J, Deloukas, Panos, Di Angelantonio, Emanuele, Ferrario, Marco, Ferrières, Jean, Franks, Paul W, Frayling, Tim M, Frossard, Philippe, Hall, Ian P, Hayward, Caroline, Jansson, Jan-Håkan, Jukema, J Wouter, Kee, Frank, Männistö, Satu, Metspalu, Andres, Munroe, Patricia B, Nordestgaard, Børge Grønne, Palmer, Colin NA, Salomaa, Veikko, Sattar, Naveed, Spector, Timothy, Strachan, David Peter, Understanding Society Scientific Group, EPIC-CVD, Van Der Harst, Pim, Zeggini, Eleftheria, Saleheen, Danish, Butterworth, Adam S, Wain, Louise V, Abecasis, Goncalo R, Danesh, John, Tobin, Martin D, Vrieze, Scott, Liu, Dajiang J, and Howson, Joanna MM

Subjects
Europe, Male, Databases, Factual, Genetic Loci, Smoking, Humans, Exome, Female, Polymorphism, Single Nucleotide, United Kingdom, 3. Good health, Biological Specimen Banks
Abstract

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

31. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Author

Erzurumluoglu, A. Mesut, Liu, Mengzhen, Jackson, Victoria E., Barnes, Daniel R., Datta, Gargi, Melbourne, Carl A., Young, Robin, Batini, Chiara, Surendran, Praveen, Jiang, Tao, Adnan, Sheikh Daud, Afaq, Saima, Agrawal, Arpana, Altmaier, Elisabeth, Antoniou, Antonis C., Asselbergs, Folkert W., Baumbach, Clemens, Bierut, Laura, Bertelsen, Sarah, Boehnke, Michael, Bots, Michiel L., Brazel, David M, Chambers, John C., Chang-Claude, Jenny, Chen, Chu, Corley, Janie, Chou, Yi-Ling, David, Sean P., De Boer, Rudolf A., De Leeuw, Christiaan A., Dennis, Joe G., Dominiczak, Anna F., Dunning, Alison M., Easton, Douglas F., Eaton, Charles, Elliott, Paul, Evangelou, Evangelos, Faul, Jessica D., Foroud, Tatiana, Goate, Alison, Gong, Jian, Grabe, Hans J., Haessler, Jeff, Haiman, Christopher, Hallmans, Göran, Hammerschlag, Anke R., Harris, Sarah E., Hattersley, Andrew, Heath, Andrew, Hsu, Chris, Iacono, William G., Kanoni, Stavroula, Kapoor, Manav, Kaprio, Jaakko, Kardia, Sharon L., Karpe, Fredrik, Kontto, Jukka, Kooner, Jaspal S., Kooperberg, Charles, Kuulasmaa, Kari, Laakso, Markku, Lai, Dongbing, Langenberg, Claudia, Le, Nhung, Lettre, Guillaume, Loukola, Anu, Luan, Jian’an, Madden, Pamela A. F., Mangino, Massimo, Marioni, Riccardo E., Marouli, Eirini, Marten, Jonathan, Martin, Nicholas G., McGue, Matt, Michailidou, Kyriaki, Mihailov, Evelin, Moayyeri, Alireza, Moitry, Marie, Müller-Nurasyid, Martina, Naheed, Aliya, Nauck, Matthias, Neville, Matthew J., Nielsen, Sune Fallgaard, North, Kari, Perola, Markus, Pharoah, Paul D. P., Pistis, Giorgio, Polderman, Tinca J., Posthuma, Danielle, Poulter, Neil, Qaiser, Beenish, Rasheed, Asif, Reiner, Alex, Renström, Frida, Rice, John, Rohde, Rebecca, Rolandsson, Olov, Samani, Nilesh J., Samuel, Maria, Schlessinger, David, Scholte, Steven H, Scott, Robert A., Sever, Peter, Shao, Yaming, Shrine, Nick, Smith, Jennifer A., Starr, John M., Stirrups, Kathleen, Stram, Danielle, Stringham, Heather M., Tachmazidou, Ioanna, Tardif, Jean-Claude, Thompson, Deborah J., Tindle, Hilary A., Tragante, Vinicius, Trompet, Stella, Turcot, Valerie, Tyrrell, Jessica, Vaartjes, Ilonca, Van Der Leij, Andries R, Van Der Meer, Peter, Varga, Tibor V., Verweij, Niek, Völzke, Henry, Wareham, Nicholas J., Warren, Helen R., Weir, David R., Weiss, Stefan, Wetherill, Leah, Yaghootkar, Hanieh, Yavas, Ersin, Jiang, Yu, Chen, Fang, Zhan, Xiaowei, Zhang, Weihua, Zhao, Wei, Zhou, Kaixin, Amouyel, Philippe, Blankenberg, Stefan, Caulfield, Mark J., Chowdhury, Rajiv, Cucca, Francesco, Deary, Ian J., Deloukas, Panos, Di Angelantonio, Emanuele, Ferrario, Marco, Ferrières, Jean, Franks, Paul W., Frayling, Tim M., Frossard, Philippe, Hall, Ian P., Hayward, Caroline, Jansson, Jan-Håkan, Jukema, J. Wouter, Kee, Frank, Männistö, Satu, Metspalu, Andres, Munroe, Patricia B., Nordestgaard, Børge Grønne, Palmer, Colin N. A., Salomaa, Veikko, Sattar, Naveed, Spector, Timothy, Strachan, David Peter, Van Der Harst, Pim, Zeggini, Eleftheria, Saleheen, Danish, Butterworth, Adam S., Wain, Louise V., Abecasis, Goncalo R., Danesh, John, Tobin, Martin D., Vrieze, Scott, Liu, Dajiang J., and Howson, Joanna M. M.

Subjects
631/208, 45, 45/43, article, 692/699/476/5, 3. Good health
Abstract

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10−8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10−8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10−3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

32. Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use

Author

Brazel, David M, Jiang, Yu, Hughey, Jordan M, Turcot, Valérie, Zhan, Xiaowei, Gong, Jian, Batini, Chiara, Weissenkampen, J Dylan, Liu, MengZhen, CHD Exome+ Consortium, Consortium For Genetics Of Smoking Behaviour, Barnes, Daniel R, Bertelsen, Sarah, Chou, Yi-Ling, Erzurumluoglu, A Mesut, Faul, Jessica D, Haessler, Jeff, Hammerschlag, Anke R, Hsu, Chris, Kapoor, Manav, Lai, Dongbing, Le, Nhung, De Leeuw, Christiaan A, Loukola, Anu, Mangino, Massimo, Melbourne, Carl A, Pistis, Giorgio, Qaiser, Beenish, Rohde, Rebecca, Shao, Yaming, Stringham, Heather, Wetherill, Leah, Zhao, Wei, Agrawal, Arpana, Bierut, Laura, Chen, Chu, Eaton, Charles B, Goate, Alison, Haiman, Christopher, Heath, Andrew, Iacono, William G, Martin, Nicholas G, Polderman, Tinca J, Reiner, Alex, Rice, John, Schlessinger, David, Scholte, H Steven, Smith, Jennifer A, Tardif, Jean-Claude, Tindle, Hilary A, Van Der Leij, Andries R, Boehnke, Michael, Chang-Claude, Jenny, Cucca, Francesco, David, Sean P, Foroud, Tatiana, Howson, Joanna MM, Kardia, Sharon LR, Kooperberg, Charles, Laakso, Markku, Lettre, Guillaume, Madden, Pamela, McGue, Matt, North, Kari, Posthuma, Danielle, Spector, Timothy, Stram, Daniel, Tobin, Martin D, Weir, David R, Kaprio, Jaakko, Abecasis, Gonçalo R, Liu, Dajiang J, and Vrieze, Scott

Subjects
Nicotine, Alcohol Drinking, Genotype, Smoking, Genetic Variation, Polymorphism, Single Nucleotide, 3. Good health, Heritability, Phenotype, Tobacco, Databases, Genetic, Behavioral genetics, GWAS, Humans, Exome, Genetic Predisposition to Disease, Alcohol, Genome-Wide Association Study, Oligonucleotide Array Sequence Analysis
Abstract

BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk. METHODS: We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci. RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals. CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.

33. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.

Author

Erzurumluoglu AM, Liu M, Jackson VE, Barnes DR, Datta G, Melbourne CA, Young R, Batini C, Surendran P, Jiang T, Adnan SD, Afaq S, Agrawal A, Altmaier E, Antoniou AC, Asselbergs FW, Baumbach C, Bierut L, Bertelsen S, Boehnke M, Bots ML, Brazel DM, Chambers JC, Chang-Claude J, Chen C, Corley J, Chou YL, David SP, de Boer RA, de Leeuw CA, Dennis JG, Dominiczak AF, Dunning AM, Easton DF, Eaton C, Elliott P, Evangelou E, Faul JD, Foroud T, Goate A, Gong J, Grabe HJ, Haessler J, Haiman C, Hallmans G, Hammerschlag AR, Harris SE, Hattersley A, Heath A, Hsu C, Iacono WG, Kanoni S, Kapoor M, Kaprio J, Kardia SL, Karpe F, Kontto J, Kooner JS, Kooperberg C, Kuulasmaa K, Laakso M, Lai D, Langenberg C, Le N, Lettre G, Loukola A, Luan J, Madden PAF, Mangino M, Marioni RE, Marouli E, Marten J, Martin NG, McGue M, Michailidou K, Mihailov E, Moayyeri A, Moitry M, Müller-Nurasyid M, Naheed A, Nauck M, Neville MJ, Nielsen SF, North K, Perola M, Pharoah PDP, Pistis G, Polderman TJ, Posthuma D, Poulter N, Qaiser B, Rasheed A, Reiner A, Renström F, Rice J, Rohde R, Rolandsson O, Samani NJ, Samuel M, Schlessinger D, Scholte SH, Scott RA, Sever P, Shao Y, Shrine N, Smith JA, Starr JM, Stirrups K, Stram D, Stringham HM, Tachmazidou I, Tardif JC, Thompson DJ, Tindle HA, Tragante V, Trompet S, Turcot V, Tyrrell J, Vaartjes I, van der Leij AR, van der Meer P, Varga TV, Verweij N, Völzke H, Wareham NJ, Warren HR, Weir DR, Weiss S, Wetherill L, Yaghootkar H, Yavas E, Jiang Y, Chen F, Zhan X, Zhang W, Zhao W, Zhao W, Zhou K, Amouyel P, Blankenberg S, Caulfield MJ, Chowdhury R, Cucca F, Deary IJ, Deloukas P, Di Angelantonio E, Ferrario M, Ferrières J, Franks PW, Frayling TM, Frossard P, Hall IP, Hayward C, Jansson JH, Jukema JW, Kee F, Männistö S, Metspalu A, Munroe PB, Nordestgaard BG, Palmer CNA, Salomaa V, Sattar N, Spector T, Strachan DP, van der Harst P, Zeggini E, Saleheen D, Butterworth AS, Wain LV, Abecasis GR, Danesh J, Tobin MD, Vrieze S, Liu DJ, and Howson JMM

Subjects
Biological Specimen Banks, Databases, Factual, Europe ethnology, Exome, Female, Humans, Male, Polymorphism, Single Nucleotide genetics, United Kingdom, Genetic Loci, Smoking genetics
Abstract

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10 -8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10 -8 ) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10 -3 ) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

Published
2020
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34. Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use.

Author

Brazel DM, Jiang Y, Hughey JM, Turcot V, Zhan X, Gong J, Batini C, Weissenkampen JD, Liu M, Barnes DR, Bertelsen S, Chou YL, Erzurumluoglu AM, Faul JD, Haessler J, Hammerschlag AR, Hsu C, Kapoor M, Lai D, Le N, de Leeuw CA, Loukola A, Mangino M, Melbourne CA, Pistis G, Qaiser B, Rohde R, Shao Y, Stringham H, Wetherill L, Zhao W, Agrawal A, Bierut L, Chen C, Eaton CB, Goate A, Haiman C, Heath A, Iacono WG, Martin NG, Polderman TJ, Reiner A, Rice J, Schlessinger D, Scholte HS, Smith JA, Tardif JC, Tindle HA, van der Leij AR, Boehnke M, Chang-Claude J, Cucca F, David SP, Foroud T, Howson JMM, Kardia SLR, Kooperberg C, Laakso M, Lettre G, Madden P, McGue M, North K, Posthuma D, Spector T, Stram D, Tobin MD, Weir DR, Kaprio J, Abecasis GR, Liu DJ, and Vrieze S

Subjects
Alcohol Drinking genetics, Databases, Genetic, Genetic Predisposition to Disease genetics, Genome-Wide Association Study statistics & numerical data, Genotype, Humans, Oligonucleotide Array Sequence Analysis statistics & numerical data, Phenotype, Polymorphism, Single Nucleotide genetics, Smoking genetics, Alcohol Drinking physiopathology, Exome, Genetic Variation physiology, Smoking physiopathology
Abstract

Background: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk., Methods: We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci., Results: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals., Conclusions: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Published
2019
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35. Nutrient intake determines post-maturity molting in the golden orb-web spider Nephila pilipes (Araneae: Araneidae).

Author

Cheng RC, Zhang S, Chen YC, Lee CY, Chou YL, Ye HY, Piorkowski D, Liao CP, and Tso IM

Subjects
Animals, Female, Sexual Behavior, Animal, Sexual Maturation, Spiders growth & development, Taiwan, Animal Nutritional Physiological Phenomena, Diet, Molting, Spiders physiology
Abstract

While molting occurs in the development of many animals, especially arthropods, post-maturity molting (PMM, organisms continue to molt after sexual maturity) has received little attention. The mechanism of molting has been studied intensively; however, the mechanism of PMM remains unknown although it is suggested to be crucial for the development of body size. In this study, we investigated factors that potentially induce PMM in the golden orb-web spider Nephila pilipes , which has the greatest degree of sexual dimorphism among terrestrial animals. We manipulated the mating history and the nutrient consumption of the females to examine whether they affect PMM. The results showed that female spiders under low nutrition were more likely to molt as adults, and mating had no significant influence on the occurrence of PMM. Moreover, spiders that underwent PMM lived longer than those that did not and their body sizes were significantly increased. Therefore, we concluded that nutritional condition rather than mating history affect PMM., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Published
2017
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