Citations 2
Optimizing Control Definitions in Opioid Use Disorder Genetic Research Using Electronic Health Records
Niarchou, Maria , Tsai, Ellen , Jennings, Mariela, Faucon, Annika, Lee, Hyunjoon, Tubbs, Justin D. , Roussos, Panos, Ge, Tian, Crist, Richard C. , Vickers‐Smith, Rachel, Edenberg, Howard, Moore, Amy, Webb, Bradley T. , Johnson, Eric, Workgroup, PsycheMERGE Substance Use Disorder, Smoller, Jordan W., Davis, Lea K., Coombes, BJ, Voloudakis, Georgios, Burstein, David , Mallard, TT, Troiani, Vanessa , Sanchez‐Roige, Sandra, Roussos, Panos , Johnson, Eric O. , Tsai, Ellen L , Tubbs, Justin D , Roussos, Panagiotis , Ge, Tian , Crist, Richard C , Vickers-Smith, Rachel , Moore, Amy , Johnson, Eric O , Kember, Rachel L , Voloudakis, Georgios , Burstein, David , Troiani, Vanessa , Sanchez-Roige, Sandra , Faucon, Annika B. , Singh, Kritika , Kember, Rachel L. , Smoller, Jordan W. , Davis, Lea Karatheodoris , Voloudakis, Georgios , Mallard, Travis T.
Addiction Biology | January 19, 2026 | Volume: 31 | Issue: 1 | Pages: No page available
ABSTRACT Amidst the opioid crisis, understanding the genetic basis of opioid use disorder (OUD) is crucial for identifying biological mechanisms and intervention points. However, genome‐wide association studies (GWASs) have been hampered by inadequate sample sizes and often the use of control populations not assessed for prior opioid exposure. Because opioid exposure is a prerequisite for the development of OUD, consideration of exposure history in controls is important. Electronic health record data (EHR) paired with genomic information allow a broader sampling of patients with OUD and exposed controls. We leveraged data across two healthcare systems to evaluate the impact of using controls not screened for opioid exposure (‘generic’) versus minimally opioid‐exposed control (‘exposed’). First, at the phenotypic level, we conducted phenome‐wide association studies (PheWAS) to compare the medical comorbidity profiles of OUD cases when using generic versus exposed controls. While PheWAS results for OUD‐related comorbidities were more pronounced when using the generic group, 83% of the disease associations were overlapping and of similar effect sizes. Second, at the genetic level, we conducted GWAS (cases vs. generic; cases vs. exposed) and assessed differences in genetic correlations and degrees of phenotypic misclassification. Genetic results were concordant across control groups based on heritability (generic: 0.16 ± 0.07 vs. 0.10 ± 0.07), associations with the coding OPRM1 variant rs1799971 ( p generic = 8.83E‐03 vs. p exposed = 1.83E‐02) and genetic correlations with prior OUD GWAS ( r g‐generic = 0.83 ± 0.26 vs. r g‐exposed = 0.78 ± 0.27). Although GWASs were limited by sample size ( N generic = 6269, N exposed = 6365), compared to an independent OUD GWAS ( N = 425 944), the dilution value for the two GWAS was not different from 1, suggesting no major impact of phenotypic misclassification. This study represents the first effort to enhance OUD genetic research through optimization of control definitions using EHR data. Generic controls ascertained within the US health systems, where exposure to prescription opioids is high, offer a practical alternative for genetic studies of OUD.
Shared genetic risk between eating disorder‐ and substance‐use‐related phenotypes: Evidence from genome‐wide association studies
Munn‐Chernoff, Melissa A. , Chou, Yi‐Ling, Coleman, Jonathan R. I. , Thornton, Laura M. , Walters, Raymond K. , Yılmaz, Zeynep , Baker, Jessica H. , Hübel, Christopher , Medland, Sarah E. , Hinney, Anke , Leppä, Virpi , Mattheisen, Manuel , Ripke, Stephan , Yao, Shuyang , Giusti‐Rodríguez, Paola , Hanscombe, Ken B. , Adan, Roger A.H. , Ando, Tetsuya , Berrettini, Wade H., Boehm, Ilka , Boni, Claudette, Perica, Vesna Boraska , Buehren, Katharina, Burghardt, Roland , Cassina, Matteo , Cichon, Sven , Clementi, Maurizio , Courtet, Philippe, Crowley, James J. , Danner, Unna N. , Davis, Oliver S. P. , Zwaan, Martina de, Degortes, Daniela, DeSocio, Janiece E., Dick, Danielle M., Dikeos, Dimitris, Dina, Christian , Dmitrzak‐Węglarz, Monika , Docampo, Elisa, Duncan, Laramie E. , Egberts, Karin , Ehrlich, Stefan , Escaramís, Geòrgia, Estivill, Xavier , Farmer, Anne, Favaro, Angela , Fernández‐Aranda, Fernando , Fichter, Manfred M., Fischer, Krista , Föcker, Manuel , Foretová, Lenka , Forstner, Andreas J. , Franklin, Christopher S., Gallinger, Steven , Giegling, Ina , Giuranna, Johanna, Gonidakis, Fragiskos , Gorwood, Philip , Mayora, Monica Gratacos, Guo, Yiran , Håkonarson, Håkon , Hatzikotoulas, Konstantinos , Hebebrand, Johannes , Helder, Sietske G., Herpertz‐Dahlmann, Beate, Herzog, Wolfgang , Huckins, Laura M. , Hudson, James I. , Imgart, Hartmut , Inoko, Hidetoshi , Janout, Vladimír , Jiménez‐Múrcia, Susana , Kalsi, Gursharan , Kaminská, Deborah , Karwautz, Andreas , Kas, Martien J. , Keski‐Rahkonen, Anna , Kiezebrink, Kirsty , Kim, Youl‐Ri , Klump, Kelly L. , Knudsen, Gun Peggy , Via, Maria C. La, Hellard, Stéphanie Le , Levitan, Robert D., Lilenfeld, Lisa , Lin, Bochao , Lissowska, Jolanta , Luykx, Jurjen J. , Magistretti, Pierre J. , Maj, Mario , Männik, Katrin , Marsal, Sara , Marshall, Christian R. , McDevitt, Sara , McGuffin, Peter, Meulenbelt, Ingrid, Navratilova, Marie, Ντάλλα, Ιωάννα , O’Toole, Julie K., Padyukov, Leonid , Palotie, Aarno , Pantel, Jacques , Papežová, Hana , Pinto, Dalila , Rabionet, Raquel , Raevuori, Anu , Ramoz, Nicolás , Reichborn‐Kjennerud, Ted , Ricca, Valdo , Ritschel, Franziska , Roberts, Marion, Rotondo, Alessandro, Rujescu, Dan, Rybakowski, Filip , Scherer, Stephen W. , Schmidt, Ulrike , Schork, Nicholas J. , Schosser, Alexandra , Šlachtová, Lenka , Landt, M , Slopien, Agnieszka, Sorbi, Sandro , Świątkowska, Beata , Szatkiewicz, Jin P., Tachmazidou, Ioanna, Tenconi, Elena, Tortorella, Alfonso , Tozzi, Federica, Treasure, Janet , Tziouvas, Konstantinos , Elburg, Annemarie , Furth, Eric F. van , Wagner, Gudrun , Walton, Esther , Widén, Elisabeth , Zerwas, Stephanie , Zipfel, Stephan, Bergen, Andrew W. , Brandt, Harry, Crawford, Steven , Halmi, Katherine A. , Johnson, Craig, Kaplan, Allan S. , Kaye, Walter H. , Mitchell, James E. , Olsen, Catherine M. , Pedersen, Nancy L. , Strober, Michael, Whiteman, David C. , Woodside, D. Blake , Grove, Jakob , Henders, Anjali K. , Larsen, Janne Tidselbak , Petersen, Liselotte , Jordan, Jennifer , Kennedy, Martin A. , Birgegård, Andreas , Landén, Mikael , Polimanti, Renato , McClintick, Jeanette N. , Adkins, Amy , Alıev, Fazil , Bacanu, Silviu‐Alin , Batzler, Anthony , Bertelsen, Sarah , Chen, Li‐Shiun , Degenhardt, Franziska , Docherty, Anna R. , Edwards, Alexis C. , Foo, Jerome C. , Fox, Louis , Frank, Josef , Hack, Laura M. , Hartmann, Annette M. , Hartz, Sarah M. , Hodgkinson, Colin A. , Hottenga, Jouke‐Jan, Konte, Bettina , Lahti, Jari , Lahti‐Pulkkinen, Marius , Ligthart, Lannie , Loukola, Anu , Maher, Brion S. , Mbarek, Hamdi , McIntosh, Andrew M. , McQueen, Matthew B. , Meyers, Jacquelyn L. , Milaneschi, Yuri , Palviainen, Teemu , Ryu, Euijung , Saccone, Nancy L. , Salvatore, Jessica E. , Streit, Fabian , Wang, Jen‐Chyong , Webb, Bradley T. , Wetherill, Leah , Wills, Amanda G. , Zhou, Hang , Boardman, Jason D., Chen, Danfeng , Copeland, William , Culverhouse, Robert , Dahmen, Norbert, Domingue, Benjamin W. , Frye, Mark A. , Gäebel, Wolfgang , Ising, Marcus, Keyes, Margaret A., Kiefer, Falk , Koller, Gabriele , Kuperman, Samuel , Lucae, Susanne , Lynskey, Michael T. , Maier, Wolfgang , Müller‐Myhsok, Bertram , Preuss, Ulrich W. , Räikkönen, Katri , Reynolds, Maureen , Ridinger, Monika , Schuckit, Marc A. , Soyka, Michael , Wodarz, Norbert , Zill, Peter , Adkins, Daniel E. , Bucholz, Kathleen K. , Diazgranados, Nancy , Goate, Alison , Goldman, David , Hancock, Dana B. , Hewitt, John K. , Johnson, Eric O. , 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. , Penninx, Brenda W.J.H. , Porjesz, Bernice , Rice, John P. , Rose, Richard J. , Shen, Pei‐Hong , Silberg, Judy L. , Tarter, Ralph E. , Vrieze, Scott , Zhao, Hongyu , Neale, Benjamin M. , Wade, Tracey , Sullivan, Patrick F., Kaprio, Jaakko , Breen, Gerome , Hottenga, Jouke‐Jan , Hakonarson, Hakon , Lissowska, Jolanta , Kennedy, Martin A , Ehrlich, Stefan , Hottenga, Jouke-Jan , Walton, Esther , Cichon, Sven , Luykx, Jurjen J , Nöthen, Markus M , Le Hellard, Stephanie , Penninx, Brenda W J H , Medland, Sarah E , Rabionet, Raquel , Estivil, Xavier , Padyukov, Leonid , Świątkowska, Beata , Dina, Christian , Palotie, Aarno V. , Ripke, Stephan , Whiteman, David C , Scherer, Stephen W , Tortorella, Alfonso , Streit, Fabian , Egberts, Karin , Goate, Alison M , Docherty, Anna R , Johnson, Eric O , Coleman, Jonathan Ri , Johnson, Emma C. , Gordon, Scott D. , Watson, Hunna J. , Gaspar, Héléna A. , Bryois, Julien , Alfredsson, Lars , Andreassen, Ole A. , Boehm, Ilka , Cone, Roger D. , Courtet, Philippe , Crow, Scott J. , Dedoussis, George , Dick, Danielle M. , Dikeos, Dimitris , Escaramís, Geòrgia , Esko, Tõnu , Forzan, Monica , Guillaume, Sébastien , Hauser, Joanna , Herms, Stefan , Herpertz-Dahlmann, Beate , Julià, Antonio , Karhunen, Leila J. , Kennedy, James L. , Li, Dong , Mattingsdal, Morten , Metspalu, Andres , Micali, Nadia , Mitchell, Karen S. , Monteleone, Alessio Maria , Monteleone, Palmiero , Nacmias, Benedetta , Ophoff, Roel A. , Ripatti, Samuli , Roberts, Marion , Santonastaso, Paolo , Scherag, André , Seitz, Jochen , Slagboom, P. Eline , Tenconi, Elena , Τσίτσικα, Άρτεμις , Tyszkiewicz‐Nwafor, Marta , Zeggini, Eleftheria , Boden, Joseph M. , Horwood, L. John , Pearson, John F , Werge, Thomas Mears , Parker, Richard , Lichtenstein, Paul , Norring, Claes E. A. , Mortensen, Preben Bo , Biernacka, Joanna M. , Bigdeli, Tim B. , Clarke, Toni‐Kim , Heilmann‐Heimbach, Stefanie , Hoffmann, Per , Lai, Dongbing , Peterson, Roseann Elizabeth , Sanchez-Roige, Sandra , Schwandt, Melanie L. , Sherva, Richard , Strohmaier, Jana , Thomas, Nathaniel , Wedow, Robbee , Boardman, Jason D., Choi, Doo‐Sup , Degenhardt, Louisa J , Hayward, Caroline , Kramer, John R. , Mann, Karl F , Männistö, Satu , Murray, Alison D. , Nurnberger, John I , Scherbaum, Norbert , Treutlein, Jens , Witt, Stephanie H. , Boomsma, Dorret I , Bierut, Laura Jean , Brown, Sandra A. , Costello, E. Jane , Wit, Harriet de , Eriksson, Johan G. , Farrer, Lindsay A. , Foroud, Tatiana , Gillespie, Nathan A. , Grucza, Richard A. , Harris, Kathleen Mullan , HESSELBROCK, VICTOR M. , Hopfer, Christian Jean , Iacono, William G. , Karpyak, Victor M. , Kendler, Kenneth S. , Kranzler, Henry R. , Palmer, Abraham A. , Rietschel, Marcella , Riley, Brien P. , Stallings, Michael C. , Vanyukov, Michael M. , Wall, Tamara L. , Whitfield, John B. , Heath, Andrew C. , Montgomery, Grant W. , Martin, Nicholas G. , Gelernter, Joel E. , Edenberg, Howard J , Bulik, Cynthia Marie , Agrawal, Arpana , Webb, Bradley T.
Addiction Biology | February 17, 2020 | Volume: 26 | Issue: 1 | Pages: No page available
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 [ r g ], 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 ( r g = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN ( r g = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating ( r g = 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 ( r gs = −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.