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1. CYP2A6 metabolism in the development of smoking behaviors in young adults

Author

Olfson, Emily, Bloom, Joseph, Bertelsen, Sarah, Budde, John P, Breslau, Naomi, Brooks, Andrew, Culverhouse, Robert, Chan, Grace, Chen, Li‐Shiun, Chorlian, David, Dick, Danielle M, Edenberg, Howard J, Hartz, Sarah, Hatsukami, Dorothy, Hesselbrock, Victor M, Johnson, Eric O, Kramer, John R, Kuperman, Samuel, Meyers, Jacquelyn L, Nurnberger, John, Porjesz, Bernice, Saccone, Nancy L, Schuckit, Marc A, Stitzel, Jerry, Tischfield, Jay A, Rice, John P, Goate, Alison, and Bierut, Laura J

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Substance Misuse, Drug Abuse (NIDA only), Cancer, Tobacco Smoke and Health, Tobacco, Genetics, Brain Disorders, Respiratory, Good Health and Well Being, Adult, Cigarette Smoking, Cytochrome P-450 CYP2A6, Female, Humans, Male, Odds Ratio, Polymorphism, Single Nucleotide, Tobacco Use Disorder, White People, Young Adult, CYP2A6, genetics, nicotine dependence, smoking, young adults, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Cytochrome P450 2A6 (CYP2A6) encodes the enzyme responsible for the majority of nicotine metabolism. Previous studies support that slow metabolizers smoke fewer cigarettes once nicotine dependent but provide conflicting results on the role of CYP2A6 in the development of dependence. By focusing on the critical period of young adulthood, this study examines the relationship of CYP2A6 variation and smoking milestones. A total of 1209 European American young adults enrolled in the Collaborative Study on the Genetics of Alcoholism were genotyped for CYP2A6 variants to calculate a previously well-validated metric that estimates nicotine metabolism. This metric was not associated with the transition from never smoking to smoking initiation nor with the transition from initiation to daily smoking (P > 0.4). But among young adults who had become daily smokers (n = 506), decreased metabolism was associated with increased risk of nicotine dependence (P = 0.03) (defined as Fagerström Test for Nicotine Dependence score ≥4). This finding was replicated in the Collaborative Genetic Study of Nicotine Dependence with 335 young adult daily smokers (P = 0.02). Secondary meta-analysis indicated that slow metabolizers had a 53 percent increased odds (OR = 1.53, 95 percent CI 1.11-2.11, P = 0.009) of developing nicotine dependence compared with normal metabolizers. Furthermore, secondary analyses examining four-level response of time to first cigarette after waking (>60, 31-60, 6-30, ≤5 minutes) demonstrated a robust effect of the metabolism metric in Collaborative Study on the Genetics of Alcoholism (P = 0.03) and Collaborative Genetic Study of Nicotine Dependence (P = 0.004), illustrating the important role of this measure of dependence. These findings highlight the complex role of CYP2A6 variation across different developmental stages of smoking behaviors.

Published
2018

2. 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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3. CYP2A6 metabolism in the development of smoking behaviors in young adults

Author

Olfson, Emily, Bloom, Joseph, Bertelsen, Sarah, Budde, John P, Breslau, Naomi, Brooks, Andrew, Culverhouse, Robert, Chan, Grace, Chen, Li-Shiun, Chorlian, David, Dick, Danielle M, Edenberg, Howard J, Hartz, Sarah, Hatsukami, Dorothy, Hesselbrock, Victor M, Johnson, Eric O, Kramer, John R, Kuperman, Samuel, Meyers, Jacquelyn L, Nurnberger, John, Porjesz, Bernice, Saccone, Nancy L, Schuckit, Marc A, Stitzel, Jerry, Tischfield, Jay A, Rice, John P, Goate, Alison, and Bierut, Laura J

Subjects
young adults, Adult, Male, CYP2A6, European Continental Ancestry Group, Psychology and Cognitive Sciences, Substance Abuse, Single Nucleotide, Tobacco Use Disorder, Medical and Health Sciences, Polymorphism, Single Nucleotide, smoking, White People, Article, Cigarette Smoking, Cytochrome P-450 CYP2A6, Young Adult, Odds Ratio, Humans, genetics, Female, Polymorphism, nicotine dependence
Abstract

Cytochrome P450 2A6 (CYP2A6) encodes the enzyme responsible for the majority of nicotine metabolism. Previous studies support that slow metabolizers smoke fewer cigarettes once nicotine dependent but provide conflicting results on the role of CYP2A6 in the development of dependence. By focusing on the critical period of young adulthood, this study examines the relationship of CYP2A6 variation and smoking milestones. A total of 1209 European American young adults enrolled in the Collaborative Study on the Genetics of Alcoholism were genotyped for CYP2A6 variants to calculate a previously well-validated metric that estimates nicotine metabolism. This metric was not associated with the transition from never smoking to smoking initiation nor with the transition from initiation to daily smoking (P > 0.4). But among young adults who had become daily smokers (n = 506), decreased metabolism was associated with increased risk of nicotine dependence (P = 0.03) (defined as Fagerström Test for Nicotine Dependence score ≥4). This finding was replicated in the Collaborative Genetic Study of Nicotine Dependence with 335 young adult daily smokers (P = 0.02). Secondary meta-analysis indicated that slow metabolizers had a 53 percent increased odds (OR = 1.53, 95 percent CI 1.11-2.11, P = 0.009) of developing nicotine dependence compared with normal metabolizers. Furthermore, secondary analyses examining four-level response of time to first cigarette after waking (>60, 31-60, 6-30, ≤5 minutes) demonstrated a robust effect of the metabolism metric in Collaborative Study on the Genetics of Alcoholism (P = 0.03) and Collaborative Genetic Study of Nicotine Dependence (P = 0.004), illustrating the important role of this measure of dependence. These findings highlight the complex role of CYP2A6 variation across different developmental stages of smoking behaviors.

Published
2016

4. CYP2A6metabolism in the development of smoking behaviors in young adults

Author

Olfson, Emily, primary, Bloom, Joseph, additional, Bertelsen, Sarah, additional, Budde, John P, additional, Breslau, Naomi, additional, Brooks, Andrew, additional, Culverhouse, Robert, additional, Chan, Grace, additional, Chen, Li-Shiun, additional, Chorlian, David, additional, Dick, Danielle M, additional, Edenberg, Howard J, additional, Hartz, Sarah, additional, Hatsukami, Dorothy, additional, Hesselbrock, Victor M, additional, Johnson, Eric O, additional, Kramer, John R, additional, Kuperman, Samuel, additional, Meyers, Jacquelyn L, additional, Nurnberger, John, additional, Porjesz, Bernice, additional, Saccone, Nancy L, additional, Schuckit, Marc A, additional, Stitzel, Jerry, additional, Tischfield, Jay A, additional, Rice, John P, additional, Goate, Alison, additional, and Bierut, Laura J, additional

Published
2016
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6. KAT2B polymorphism identified for drug abuse in African Americans with regulatory links to drug abuse pathways in human prefrontal cortex.

Author

Johnson, Eric O., Hancock, Dana B., Levy, Joshua L., Gaddis, Nathan C., Page, Grier P., Glasheen, Cristie, Saccone, Nancy L., Bierut, Laura J., and Kral, Alex H.

Subjects
GENETIC polymorphisms, SUBSTANCE abuse, AFRICAN Americans, DRUG abuse, GENE expression, BLACK people, DISEASE susceptibility, FRONTAL lobe, RESEARCH funding, TRANSFERASES, WHITE people, CITY dwellers, SEQUENCE analysis
Abstract

Drug abuse is a common and heritable set of disorders, but the underlying genetic factors are largely unknown. We conducted genome-wide association studies of drug abuse using 7 million imputed single nucleotide polymorphisms (SNPs) and insertions/deletions in African Americans (AAs; n = 3742) and European Americans (EAs; n = 6845). Cases were drawn from the Urban Health Study of street-recruited people, who injected drugs and reported abusing opioids, cocaine, marijuana, stimulants and/or other drugs 10 or more times in the past 30 days, and were compared with population controls. Independent replication testing was conducted in 755 AAs and 1131 EAs from the Genetic Association Information Network. An intronic SNP (rs9829896) in the K(lysine) acetyltransferase 2B (KAT2B) gene was significantly associated with drug abuse in AAs (P = 4.63 × 10-8 ) and independently replicated in AAs (P = 0.0019). The rs9829896-C allele (frequency = 12%) had odds ratios of 0.68 and 0.53 across the AA cohorts: meta-analysis P = 3.93 × 10-10 . Rs9829896-C was not associated with drug abuse across the EA cohorts: frequency = 36% and meta-analysis P = 0.12. Using dorsolateral prefrontal cortex data from the BrainCloud cohort, we found that rs9829896-C was associated with reduced KAT2B expression in AAs (n = 113, P = 0.050) but not EAs (n = 110, P = 0.39). KAT2B encodes a transcriptional regulator in the cyclic adenosine monophosphate and dopamine signaling pathways, and rs9829896-C was associated with expression of genes in these pathways: reduced CREBBP expression (P = 0.011) and increased OPRM1 expression (P = 0.016), both in AAs only. Our study identified the KAT2B SNP rs9829896 as having novel and biologically plausible associations with drug abuse and gene expression in AAs but not EAs, suggesting ancestry-specific effects. [ABSTRACT FROM AUTHOR]

Published
2016
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8. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies.

Author

Munn-Chernoff MA, Johnson EC, Chou YL, Coleman JRI, Thornton LM, Walters RK, Yilmaz Z, Baker JH, Hübel C, Gordon S, Medland SE, Watson HJ, Gaspar HA, Bryois J, Hinney A, Leppä VM, Mattheisen M, Ripke S, Yao S, Giusti-Rodríguez P, Hanscombe KB, Adan RAH, Alfredsson L, Ando T, Andreassen OA, Berrettini WH, Boehm I, Boni C, Boraska Perica V, Buehren K, Burghardt R, Cassina M, Cichon S, Clementi M, Cone RD, Courtet P, Crow S, Crowley JJ, Danner UN, Davis OSP, de Zwaan M, Dedoussis G, Degortes D, DeSocio JE, Dick DM, Dikeos D, Dina C, Dmitrzak-Weglarz M, Docampo E, Duncan LE, Egberts K, Ehrlich S, Escaramís G, Esko T, Estivill X, Farmer A, Favaro A, Fernández-Aranda F, Fichter MM, Fischer K, Föcker M, Foretova L, Forstner AJ, Forzan M, Franklin CS, Gallinger S, Giegling I, Giuranna J, Gonidakis F, Gorwood P, Gratacos Mayora M, Guillaume S, Guo Y, Hakonarson H, Hatzikotoulas K, Hauser J, Hebebrand J, Helder SG, Herms S, Herpertz-Dahlmann B, Herzog W, Huckins LM, Hudson JI, Imgart H, Inoko H, Janout V, Jiménez-Murcia S, Julià A, Kalsi G, Kaminská D, Karhunen L, Karwautz A, Kas MJH, Kennedy JL, Keski-Rahkonen A, Kiezebrink K, Kim YR, Klump KL, Knudsen GPS, La Via MC, Le Hellard S, Levitan RD, Li D, Lilenfeld L, Lin BD, Lissowska J, Luykx J, Magistretti PJ, Maj M, Mannik K, Marsal S, Marshall CR, Mattingsdal M, McDevitt S, McGuffin P, Metspalu A, Meulenbelt I, Micali N, Mitchell K, Monteleone AM, Monteleone P, Nacmias B, Navratilova M, Ntalla I, O'Toole JK, Ophoff RA, Padyukov L, Palotie A, Pantel J, Papezova H, Pinto D, Rabionet R, Raevuori A, Ramoz N, Reichborn-Kjennerud T, Ricca V, Ripatti S, Ritschel F, Roberts M, Rotondo A, Rujescu D, Rybakowski F, Santonastaso P, Scherag A, Scherer SW, Schmidt U, Schork NJ, Schosser A, Seitz J, Slachtova L, Slagboom PE, Slof-Op't Landt MCT, Slopien A, Sorbi S, Świątkowska B, Szatkiewicz JP, Tachmazidou I, Tenconi E, Tortorella A, Tozzi F, Treasure J, Tsitsika A, Tyszkiewicz-Nwafor M, Tziouvas K, van Elburg AA, van Furth EF, Wagner G, Walton E, Widen E, Zeggini E, Zerwas S, Zipfel S, Bergen AW, Boden JM, Brandt H, Crawford S, Halmi KA, Horwood LJ, Johnson C, Kaplan AS, Kaye WH, Mitchell J, Olsen CM, Pearson JF, Pedersen NL, Strober M, Werge T, Whiteman DC, Woodside DB, Grove J, Henders AK, Larsen JT, Parker R, Petersen LV, Jordan J, Kennedy MA, Birgegård A, Lichtenstein P, Norring C, Landén M, Mortensen PB, Polimanti R, McClintick JN, Adkins AE, Aliev F, Bacanu SA, Batzler A, Bertelsen S, Biernacka JM, Bigdeli TB, Chen LS, Clarke TK, Degenhardt F, Docherty AR, Edwards AC, Foo JC, Fox L, Frank J, Hack LM, Hartmann AM, Hartz SM, Heilmann-Heimbach S, Hodgkinson C, Hoffmann P, Hottenga JJ, Konte B, Lahti J, Lahti-Pulkkinen M, Lai D, Ligthart L, Loukola A, Maher BS, Mbarek H, McIntosh AM, McQueen MB, Meyers JL, Milaneschi Y, Palviainen T, Peterson RE, Ryu E, Saccone NL, Salvatore JE, Sanchez-Roige S, Schwandt M, Sherva R, Streit F, Strohmaier J, Thomas N, Wang JC, Webb BT, Wedow R, Wetherill L, Wills AG, Zhou H, Boardman JD, Chen D, Choi DS, Copeland WE, Culverhouse RC, Dahmen N, Degenhardt L, Domingue BW, Frye MA, Gäebel W, Hayward C, Ising M, Keyes M, Kiefer F, Koller G, Kramer J, Kuperman S, Lucae S, Lynskey MT, Maier W, Mann K, Männistö S, Müller-Myhsok B, Murray AD, Nurnberger JI, Preuss U, Räikkönen K, Reynolds MD, Ridinger M, Scherbaum N, Schuckit MA, Soyka M, Treutlein J, Witt SH, Wodarz N, Zill P, Adkins DE, Boomsma DI, Bierut LJ, Brown SA, Bucholz KK, Costello EJ, de Wit H, Diazgranados N, Eriksson JG, Farrer LA, Foroud TM, Gillespie NA, Goate AM, Goldman D, Grucza RA, Hancock DB, Harris KM, Hesselbrock V, Hewitt JK, Hopfer CJ, Iacono WG, Johnson EO, Karpyak VM, Kendler KS, Kranzler HR, Krauter K, Lind PA, McGue M, MacKillop J, Madden PAF, Maes HH, Magnusson PKE, Nelson EC, Nöthen MM, Palmer AA, Penninx BWJH, Porjesz B, Rice JP, Rietschel M, Riley BP, Rose RJ, Shen PH, Silberg J, Stallings MC, Tarter RE, Vanyukov MM, Vrieze S, Wall TL, Whitfield JB, Zhao H, Neale BM, Wade TD, Heath AC, Montgomery GW, Martin NG, Sullivan PF, Kaprio J, Breen G, Gelernter J, Edenberg HJ, Bulik CM, and Agrawal A

Subjects
Alcoholism genetics, Depressive Disorder, Major genetics, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Schizophrenia genetics, Tobacco Use Disorder genetics, Feeding and Eating Disorders genetics, Substance-Related Disorders genetics
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., (© 2020 Society for the Study of Addiction.)

Published
2021
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