Browsing by Author "Hartmann, Annette M."

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    Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts
    (Springer, 2016-03) Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun; Hartz, Sarah M.; Culverhouse, Robert C.; Chen, Xiangning; Coon, Hilary; Frank, Josef; Kamens, Helen M.; Konte, Bettina; Kovanen, Leena; Latvala, Antti; Legrand, Lisa N.; Maher, Brion S.; Melroy, Whitney E.; Nelson, Elliot C.; Reid, Mark W.; Robinson, Jason D.; Shen, Pei-Hong; Yang, Bao-Zhu; Andrews, Judy A.; Aveyard, Paul; Beltcheva, Olga; Brown, Sandra A.; Cannon, Dale S.; Cichon, Sven; Corley, Robin P.; Dahmen, Norbert; Degenhardt, Louisa; Foroud, Tatiana; Gaebel, Wolfgang; Giegling, Ina; Glatt, Stephen J.; Grucza, Richard A.; Hardin, Jill; Hartmann, Annette M.; Heath, Andrew C.; Herms, Stefan; Hodgkinson, Colin A.; Hoffmann, Per; Hops, Hyman; Huizinga, David; Ising, Marcus; Johnson, Eric O.; Johnstone, Elaine; Kaneva, Radka P.; Kendler, Kenneth S.; Kiefer, Falk; Kranzler, Henry R.; Krauter, Ken S.; Levran, Orna; Lucae, Susanne; Lynskey, Michael T.; Maier, Wolfgang; Mann, Karl; Martin, Nicholas G.; Mattheisen, Manuel; Montgomery, Grant W.; Müller-Myhsok, Bertram; Murphy, Michael F.; Neale, Michael C.; Nikolov, Momchil A.; Nishita, Denise; Nöthen, Markus M.; Nurnberger, John; Partonen, Timo; Pergadia, Michele L.; Reynolds, Maureen; Ridinger, Monika; Rose, Richard J.; Rouvinen-Lagerström, Noora; Scherbaum, Norbert; Schmäl, Christine; Soyka, Michael; Stallings, Michael C.; Steffens, Michael; Treutlein, Jens; Tsuang, Ming; Wallace, Tamara L.; Wodarz, Norbert; Yuferov, Vadim; Zill, Peter; Bergen, Andrew W.; Chen, Jingchun; Cinciripini, Paul M.; Edenberg, Howard J.; Ehringer, Marissa A.; Ferrell, Robert E.; Gelernter, Joel; Goldman, David; Hewitt, John K.; Hopfer, Christian J.; Iacono, William G.; Kaprio, Jaakko; Kreek, Mary Jeanne; Kremensky, Ivo M.; Madden, Pamela A.F.; McGue, Matt; Munafò, Marcus R.; Philibert, Robert A.; Rietschel, Marcella; Roy, Alec; Rujescu, Dan; Saarikoski, Sirkku T.; Swan, Gary E.; Todorov, Alexandre A.; Vanyukov, Michael M.; Weiss, Robert B.; Bierut, Laura J.; Saccone, Nancy L.; Department of Medical & Molecular Genetics, IU School of Medicine
    The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83-0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses.
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    Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
    (Springer Nature, 2019-03) Kunkle, Brian W.; Grenier-Boley, Benjamin; Sims, Rebecca; Bis, Joshua C.; Damotte, Vincent; Naj, Adam C.; Boland, Anne; Vronskaya, Maria; van der Lee, Sven J.; Amlie-Wolf, Alexandre; Bellenguez, Céline; Frizatti, Aura; Chouraki, Vincent; Martin, Eden R.; Sleegers, Kristel; Badarinarayan, Nandini; Jakobsdottir, Johanna; Hamilton-Nelson, Kara L.; Moreno-Grau, Sonia; Olaso, Robert; Raybould, Rachel; Chen, Yuning; Kuzma, Amanda B.; Hiltunen, Mikko; Morgan, Taniesha; Ahmad, Shahzad; Vardarajan, Badri N.; Epelbaum, Jacques; Hoffmann, Per; Boada, Merce; Beecham, Gary W.; Garnier, Jean-Guillaume; Harold, Denise; Fitzpatrick, Annette L.; Valladares, Otto; Moutet, Marie-Laure; Gerrish, Amy; Smith, Albert V.; Qu, Liming; Bacq, Delphine; Denning, Nicola; Jian, Xueqiu; Zhao, Yi; Del Zompo, Maria; Fox, Nick C.; Choi, Seung-Hoan; Mateo, Ignacio; Hughes, Joseph T.; Adams, Hieab H.; Malamon, John; Sanchez-Garcia, Florentino; Patel, Yogen; Brody, Jennifer A.; Dombroski, Beth A.; Deniz Naranjo, Maria Candida; Daniilidou, Makrina; Eiriksdottir, Gudny; Mukherjee, Shubhabrata; Wallon, David; Uphill, James; Aspelund, Thor; Cantwell, Laura B.; Garzia, Fabienne; Galimberti, Daniela; Hofer, Edith; Butkiewicz, Mariusz; Fin, Bertrand; Scarpini, Elio; Sarnowski, Chloe; Bush, Will S.; Meslage, Stéphane; Kornhuber, Johannes; White, Charles C.; Song, Yuenjoo; Barber, Robert C.; Engelborghs, Sebastiaan; Sordon, Sabrina; Voijnovic, Dina; Adams, Perrie M.; Vandenberghe, Rik; Mayhaus, Manuel; Cupples, L. Adrienne; Albert, Marilyn S.; De Deyn, Peter P.; Gu, Wei; Himali, Jayanadra J.; Beekly, Duane; Squassina, Alessio; Hartmann, Annette M.; Orellana, Adelina; Blacker, Deborah; Rodriguez-Rodriguez, Eloy; Lovestone, Simon; Garcia, Melissa E.; Doody, Rachelle S.; Munoz-Fernadez, Carmen; Sussams, Rebecca; Lin, Honghuang; Fairchild, Thomas J.; Benit, Yolanda A.; Holmes, Clive; Karamujić-Čomić, Hata; Frosch, Matthew P.; Thonberg, Hakan; Maier, Wolfgang; Roshchupkin, Gennady; Ghetti, Bernardino; Giedraitis, Vilmantas; Kawalia, Amit; Li, Shuo; Huebinger, Ryan M.; Kilander, Lena; Moebus, Susanne; Hernández, Isabel; Kamboh, M. Ilyas; Brundin, RoseMarie; Turton, James; Yang, Qiong; Katz, Mindy J.; Concari, Letizia; Lord, Jenny; Beiser, Alexa S.; Keene, C. Dirk; Helisalmi, Seppo; Kloszewska, Iwona; Kukull, Walter A.; Koivisto, Anne Maria; Lynch, Aoibhinn; Tarraga, Lluís; Larson, Eric B.; Haapasalo, Annakaisa; Lawlor, Brian; Mosley, Thomas H.; Lipton, Richard B.; Solfrizzi, Vincenzo; Gill, Michael; Longstreth, W. T., Jr.; Montine, Thomas J.; Frisardi, Vincenza; Diez-Fairen, Monica; Rivadeneira, Fernando; Petersen, Ronald C.; Deramecourt, Vincent; Alvarez, Ignacio; Salani, Francesca; Ciaramella, Antonio; Boerwinkle, Eric; Reiman, Eric M.; Fievet, Nathalie; Rotter, Jerome I.; Reisch, Joan S.; Hanon, Olivier; Cupidi, Chiara; Uitterlinden, A. G. Andre; Royall, Donald R.; Dufouil, Carole; Maletta, Raffaele Giovanni; de Rojas, Itziar; Sano, Mary; Brice, Alexis; Cecchetti, Roberta; St. George-Hyslop, Peter; Ritchie, Karen; Tsolaki, Magda; Tsuang, Debby W.; Dubois, Bruno; Craig, David; Wu, Chuang-Kuo; Soininen, Hilkka; Avramidou, Despoina; Albin, Roger L.; Fratiglioni, Laura; Germanou, Antonia; Apostolova, Liana G.; Keller, Lina; Koutroumani, Maria; Arnold, Steven E.; Panza, Francesco; Gkatzima, Olymbia; Asthana, Sanjay; Hannequin, Didier; Whitehead, Patrice; Atwood, Craig S.; Caffarra, Paolo; Hampel, Harald; Quintela, Inés; Carracedo, Ángel; Lannfelt, Lars; Rubinsztein, David C.; Barnes, Lisa L.; Pasquier, Florence; Frölich, Lutz; Barral, Sandra; McGuinness, Bernadette; Beach, Thomas G .; Johnston, Janet A.; Becker, James T.; Passmore, Peter; Bigio, Eileen H.; Schott, Jonathan M.; Bird, Thomas D.; Warren, Jason D.; Boeve, Bradley F.; Lupton, Michelle K.; Bowen, James D.; Proitsi, Petra; Boxer, Adam; Powell, John F.; Burke, James R.; Kauwe, John S.K.; Burns, Jeffrey M.; Mancuso, Michelangelo; Buxbaum, Joseph D.; Bonuccelli, Ubaldo; Cairns, Nigel J.; McQuillin, Andrew; Cao, Chuanhai; Livingston, Gill; Carlson, Chris S.; Bass, Nicholas J.; Carlsson, Cynthia M.; Hardy, John; Carney, Regina M.; Bras, Jose; Carrasquillo, Minerva M.; Guerreiro, Rita; Allen, Mariet; Chui, Helena C.; Fisher, Elizabeth; Masullo, Carlo; Crocco, Elizabeth A.; DeCarli, Charles; Bisceglio, Gina; Dick, Malcolm; Ma, Li; Duara, Ranjan; Graff-Radford, Neill R.; Evans, Denis A.; Hodges, Angela; Faber, Kelley M.; Scherer, Martin; Fallon, Kenneth B.; Riemenschneider, Matthias; Fardo, David W.; Heun, Reinhard; Farlow, Martin R.; Kölsch, Heike; Ferris, Steven; Leber, Markus; Foroud, Tatiana M.; Heuser, Isabella; Galasko, Douglas R.; Giegling, Ina; Gearing, Marla; Hüll, Michael; Geschwind, Daniel H.; Gilbert, John R.; Morris, John; Green, Robert C.; Mayo, Kevin; Growdon, John H.; Feulner, Thomas; Hamilton, Ronald L.; Harrell, Lindy E.; Drichel, Dmitriy; Honig, Lawrence S.; Cushion, Thomas D.; Huentelman, Matthew J.; Hollingworth, Paul; Hulette, Christine M.; Hyman, Bradley T.; Marshall, Rachel; Jarvik, Gail P.; Meggy, Alun; Abner, Erin; Menzies, Georgina E.; Jin, Lee-Way; Leonenko, Ganna; Real, Luis M.; Jun, Gyungah R.; Baldwin, Clinton T.; Grozeva, Detelina; Karydas, Anna; Russo, Giancarlo; Kaye, Jeffrey A.; Kim, Ronald; Jessen, Frank; Kowall, Neil W.; Vellas, Bruno; Kramer, Joel H.; Vardy, Emma; LaFerla, Frank M.; Jöckel, Karl-Heinz; Lah, James J.; Dichgans, Martin; Leverenz, James B.; Mann, David; Levey, Allan I.; Pickering-Brown, Stuart; Lieberman, Andrew P.; Klopp, Norman; Lunetta, Kathryn L.; Wichmann, H-Erich; Lyketsos, Constantine G.; Morgan, Kevin; Marson, Daniel C.; Brown, Kristelle; Martiniuk, Frank; Medway, Christopher; Mash, Deborah C.; Nöthen, Markus M.; Masliah, Eliezer; Hooper, Nigel M.; McCormick, Wayne C.; Daniele, Antonio; McCurry, Susan M.; Bayer, Anthony; McDavid, Andrew N.; Gallacher, John; McKee, Ann C.; van den Bussche, Hendrik; Mesulam, Marsel; Brayne, Carol; Miller, Bruce L.; Riedel-Heller, Steffi; Miller, Carol A.; Miller, Joshua W.; Al-Chalabi, Ammar; Morris, John C.; Shaw, Christopher E.; Myers, Amanda J.; Wiltfang, Jens; O'Bryant, Sid; Olichney, John M.; Alvarez, Victoria; Parisi, Joseph E.; Singleton, Andrew B.; Paulson, Henry L.; Collinge, John; Perry, William R.; Mead, Simon; Peskind, Elaine; Cribbs, David H.; Rossor, Martin; Pierce, Aimee; Ryan, Natalie S.; Poon, Wayne W.; Nacmias, Benedetta; Potter, Huntington; Sorbi, Sandro; Quinn, Joseph F.; Sacchinelli, Eleonora; Raj, Ashok; Spalletta, Gianfranco; Raskind, Murray; Caltagirone, Carlo; Bossù, Paola; Orfei, Maria Donata; Reisberg, Barry; Clarke, Robert; Reitz, Christiane; Smith, A. David; Ringman, John M.; Warden, Donald; Roberson, Erik D.; Wilcock, Gordon; Rogaeva, Ekaterina; Bruni, Amalia Cecilia; Rosen, Howard J.; Gallo, Maura; Rosenberg, R.N.; Ben-Shlomo, Yoav; Sager, Mark A.; Mecocci, Patrizia; Saykin, Andrew J.; Pastor, Pau; Cuccaro, Michael L.; Vance, Jeffery M.; Schneider, Julie A.; Schneider, Lori S.; Slifer, Susan; Seeley, William W.; Smith, Amanda G.; Sonnen, Joshua A.; Spina, Salvatore; Stern, Robert A.; Swerdlow, Russell H.; Tang, Mitchell; Tanzi, Rudolph E.; Trojanowski, John Q.; Troncoso, Juan C.; Van Deerlin, Vivianna M.; Van Eldik, Linda J.; Vinters, Harry V.; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A.; Wilhelmsen, Kirk C.; Williamson, Jennifer; Wingo, Thomas S.; Woltjer, Randall L.; Wright, Clinton B.; Yu, Chang-En; Yu, Lei; Saba, Yasaman; Pilotto, Alberto; Bullido, Maria J.; Peters, Oliver; Crane, Paul K.; Bennett, David; Bosco, Paola; Coto, Eliecer; Boccardi, Virginia; De Jager, Phil L.; Lleo, Alberto; Warner, Nick; Lopez, Oscar L.; Ingelsson, Martin; Deloukas, Panagiotis; Cruchaga, Carlos; Graff, Caroline; Gwilliam, Rhian; Fornage, Myriam; Goate, Alison M.; Sanchez-Juan, Pascual; Kehoe, Patrick G.; Amin, Najaf; Ertekin-Taner, Nilifur; Berr, Claudine; Debette, Stéphanie; Love, Seth; Launer, Lenore J.; Younkin, Steven G.; Dartigues, Jean-Francois; Corcoran, Chris; Ikram, M. Arfan; Dickson, Dennis W.; Nicolas, Gael; Campion, Dominique; Tschanz, JoAnn; Schmidt, Helena; Hakonarson, Hakon; Clarimon, Jordi; Munger, Ron; Schmidt, Reinhold; Farrer, Lindsay A.; Van Broeckhoven, Christine; O'Donovan, Michael C.; DeStefano, Anita L.; Jones, Lesley; Haines, Jonathan L.; Deleuze, Jean-Francois; Owen, Michael J.; Gudnason, Vilmundur; Mayeux, Richard; Escott-Price, Valentina; Psaty, Bruce M.; Ramirez, Alfredo; Wang, Li-San; Ruiz, Agustin; van Duijn, Cornelia M.; Holmans, Peter A.; Seshadri, Sudha; Williams, Julie; Amouyel, Phillippe; Schellenberg, Gerard D.; Lambert, Jean-Charles; Pericak-Vance, Margaret A.; Pathology and Laboratory Medicine, School of Medicine
    Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
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    Genome-wide association study identifies 48 common genetic variants associated with handedness
    (Springer Nature, 2021) Cuellar-Partida, Gabriel; Tung, Joyce Y.; Eriksson, Nicholas; Albrecht, Eva; Aliev, Fazil; Andreassen, Ole A.; Barroso, Inês; Beckmann, Jacques S.; Boks, Marco P.; Boomsma, Dorret I.; Boyd, Heather A.; Breteler, Monique M. B.; Campbell, Harry; Chasman, Daniel I.; Cherkas, Lynn F.; Davies, Gail; de Geus, Eco J. C.; Deary, Ian J.; Deloukas, Panos; Dick, Danielle M.; Duffy, David L.; Eriksson, Johan G.; Esko, Tõnu; Feenstra, Bjarke; Geller, Frank; Gieger, Christian; Giegling, Ina; Gordon, Scott D.; Han, Jiali; Hansen, Thomas F.; Hartmann, Annette M.; Hayward, Caroline; Heikkilä, Kauko; Hicks, Andrew A.; Hirschhorn, Joel N.; Hottenga, Jouke-Jan; Huffman, Jennifer E.; Hwang, Liang-Dar; Ikram, M. Arfan; Kaprio, Jaakko; Kemp, John P.; Khaw, Kay-Tee; Klopp, Norman; Konte, Bettina; Kutalik, Zoltan; Lahti, Jari; Li, Xin; Loos, Ruth J. F.; Luciano, Michelle; Magnusson, Sigurdur H.; Mangino, Massimo; Marques-Vidal, Pedro; Martin, Nicholas G.; McArdle, Wendy L.; McCarthy, Mark I.; Medina-Gomez, Carolina; Melbye, Mads; Melville, Scott A.; Metspalu, Andres; Milani, Lili; Mooser, Vincent; Nelis, Mari; Nyholt, Dale R.; O'Connell, Kevin S.; Ophoff, Roel A.; Palmer, Cameron; Palotie, Aarno; Palviainen, Teemu; Pare, Guillaume; Paternoster, Lavinia; Peltonen, Leena; Penninx, Brenda W. J. H.; Polasek, Ozren; Pramstaller, Peter P.; Prokopenko, Inga; Raikkonen, Katri; Ripatti, Samuli; Rivadeneira, Fernando; Rudan, Igor; Rujescu, Dan; Smit, Johannes H.; Smith, George Davey; Smoller, Jordan W.; Soranzo, Nicole; Spector, Tim D.; St. Pourcain, Beate; Starr, John M.; Stefánsson, Hreinn; Steinberg, Stacy; Teder-Laving, Maris; Thorleifsson, Gudmar; Stefánsson, Kári; Timpson, Nicholas J.; Uitterlinden, André G.; van Duijn, Cornelia M.; van Rooij, Frank J. A.; Vink, Jaqueline M.; Vollenweider, Peter; Vuoksimaa, Eero; Waeber, Gérard; Wareham, Nicholas J.; Warrington, Nicole; Waterworth, Dawn; Werge, Thomas; Wichmann, H-Erich; Widen, Elisabeth; Willemsen, Gonneke; Wright, Alan F.; Wright, Margaret J.; Xu, Mousheng; Zhao, Jing Hua; Kraft, Peter; Hinds, David A.; Lindgren, Cecilia M.; Mägi, Reedik; Neale, Benjamin M.; Evans, David M.; Medland, Sarah E.; Epidemiology, School of Public Health
    Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10-8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.
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    GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors
    (American Psychiatric Association, 2023) Docherty, Anna R.; Mullins, Niamh; Ashley-Koch, Allison E.; Qin, Xuejun; Coleman, Jonathan R. I.; Shabalin, Andrey; Kang, JooEun; Murnyak, Balasz; Wendt, Frank; Adams, Mark; Campos, Adrian I.; DiBlasi, Emily; Fullerton, Janice M.; Kranzler, Henry R.; Bakian, Amanda V.; Monson, Eric T.; Rentería, Miguel E.; Walss-Bass, Consuelo; Andreassen, Ole A.; Behera, Chittaranjan; Bulik, Cynthia M.; Edenberg, Howard J.; Kessler, Ronald C.; Mann, J. John; Nurnberger, John I., Jr.; Pistis, Giorgio; Streit, Fabian; Ursano, Robert J.; Polimanti, Renato; Dennis, Michelle; Garrett, Melanie; Hair, Lauren; Harvey, Philip; Hauser, Elizabeth R.; Hauser, Michael A.; Huffman, Jennifer; Jacobson, Daniel; Madduri, Ravi; McMahon, Benjamin; Oslin, David W.; Trafton, Jodie; Awasthi, Swapnil; Berrettini, Wade H.; Bohus, Martin; Chang, Xiao; Chen, Hsi-Chung; Chen, Wei J.; Christensen, Erik D.; Crow, Scott; Duriez, Philibert; Edwards, Alexis C.; Fernández-Aranda, Fernando; Galfalvy, Hanga; Gandal, Michael; Gorwood, Philip; Guo, Yiran; Hafferty, Jonathan D.; Hakonarson, Hakon; Halmi, Katherine A.; Hishimoto, Akitoyo; Jain, Sonia; Jamain, Stéphane; Jiménez-Murcia, Susana; Johnson, Craig; Kaplan, Allan S.; Kaye, Walter H.; Keel, Pamela K.; Kennedy, James L.; Kim, Minsoo; Klump, Kelly L.; Levey, Daniel F.; Li, Dong; Liao, Shih-Cheng; Lieb, Klaus; Lilenfeld, Lisa; Marshall, Christian R.; Mitchell, James E.; Okazaki, Satoshi; Otsuka, Ikuo; Pinto, Dalila; Powers, Abigail; Ramoz, Nicolas; Ripke, Stephan; Roepke, Stefan; Rozanov, Vsevolod; Scherer, Stephen W.; Schmahl, Christian; Sokolowski, Marcus; Starnawska, Anna; Strober, Michael; Su, Mei-Hsin; Thornton, Laura M.; Treasure, Janet; Ware, Erin B.; Watson, Hunna J.; Witt, Stephanie H.; Woodside, D. Blake; Yilmaz, Zeynep; Zillich, Lea; Adolfsson, Rolf; Agartz, Ingrid; Alda, Martin; Alfredsson, Lars; Appadurai, Vivek; Artigas, María Soler; Van der Auwera, Sandra; Azevedo, M. Helena; Bass, Nicholas; Bau, Claiton H. D.; Baune, Bernhard T.; Bellivier, Frank; Berger, Klaus; Biernacka, Joanna M.; Bigdeli, Tim B.; Binder, Elisabeth B.; Boehnke, Michael; Boks, Marco P.; Braff, David L.; Bryant, Richard; Budde, Monika; Byrne, Enda M.; Cahn, Wiepke; Castelao, Enrique; Cervilla, Jorge A.; Chaumette, Boris; Corvin, Aiden; Craddock, Nicholas; Djurovic, Srdjan; Foo, Jerome C.; Forstner, Andreas J.; Frye, Mark; Gatt, Justine M.; Giegling, Ina; Grabe, Hans J.; Green, Melissa J.; Grevet, Eugenio H.; Grigoroiu-Serbanescu, Maria; Gutierrez, Blanca; Guzman-Parra, Jose; Hamshere, Marian L.; Hartmann, Annette M.; Hauser, Joanna; Heilmann-Heimbach, Stefanie; Hoffmann, Per; Ising, Marcus; Jones, Ian; Jones, Lisa A.; Jonsson, Lina; Kahn, René S.; Kelsoe, John R.; Kendler, Kenneth S.; Kloiber, Stefan; Koenen, Karestan C.; Kogevinas, Manolis; Krebs, Marie-Odile; Landén, Mikael; Leboyer, Marion; Lee, Phil H.; Levinson, Douglas F.; Liao, Calwing; Lissowska, Jolanta; Mayoral, Fermin; McElroy, Susan L.; McGrath, Patrick; McGuffin, Peter; McQuillin, Andrew; Mehta, Divya; Melle, Ingrid; Mitchell, Philip B.; Molina, Esther; Morken, Gunnar; Nievergelt, Caroline; Nöthen, Markus M.; O'Donovan, Michael C.; Ophoff, Roel A.; Owen, Michael J.; Pato, Carlos; Pato, Michele T.; Penninx, Brenda W. J. H.; Potash, James B.; Power, Robert A.; Preisig, Martin; Quested, Digby; Ramos-Quiroga, Josep Antoni; Reif, Andreas; Ribasés, Marta; Richarte, Vanesa; Rietschel, Marcella; Rivera, Margarita; Roberts, Andrea; Roberts, Gloria; Rouleau, Guy A.; Rovaris, Diego L.; Sanders, Alan R.; Schofield, Peter R.; Schulze, Thomas G.; Scott, Laura J.; Serretti, Alessandro; Shi, Jianxin; Sirignano, Lea; Sklar, Pamela; Smeland, Olav B.; Smoller, Jordan W.; Sonuga-Barke, Edmund J. S.; Trzaskowski, Maciej; Tsuang, Ming T.; Turecki, Gustavo; Vilar-Ribó, Laura; Vincent, John B.; Völzke, Henry; Walters, James T. R.; Weickert, Cynthia Shannon; Weickert, Thomas W.; Weissman, Myrna M.; Williams, Leanne M.; Wray, Naomi R.; Zai, Clement C.; Agerbo, Esben; Børglum, Anders D.; Breen, Gerome; Demontis, Ditte; Erlangsen, Annette; Gelernter, Joel; Glatt, Stephen J.; Hougaard, David M.; Hwu, Hai-Gwo; Kuo, Po-Hsiu; Lewis, Cathryn M.; Li, Qingqin S.; Liu, Chih-Min; Martin, Nicholas G.; McIntosh, Andrew M.; Medland, Sarah E.; Mors, Ole; Nordentoft, Merete; Olsen, Catherine M.; Porteous, David; Smith, Daniel J.; Stahl, Eli A.; Stein, Murray B.; Wasserman, Danuta; Werge, Thomas; Whiteman, David C.; Willour, Virginia; VA Million Veteran Program (MVP); MVP Suicide Exemplar Workgroup; Suicide Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Eating Disorder Working Group of the Psychiatric Genomics Consortium; German Borderline Genomics Consortium; Coon, Hilary; Beckham, Jean C.; Kimbrel, Nathan A.; Ruderfer, Douglas M.; Psychiatry, School of Medicine
    Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. Methods: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. Results: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. Conclusions: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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    New insights into the genetic etiology of Alzheimer's disease and related dementias
    (Springer Nature, 2022) Bellenguez, Céline; Küçükali, Fahri; Jansen, Iris E.; Kleineidam, Luca; Moreno-Grau, Sonia; Amin, Najaf; Naj, Adam C.; Campos-Martin, Rafael; Grenier-Boley, Benjamin; Andrade, Victor; Holmans, Peter A.; Boland, Anne; Damotte, Vincent; van der Lee, Sven J.; Costa, Marcos R.; Kuulasmaa, Teemu; Yang, Qiong; de Rojas, Itziar; Bis, Joshua C.; Yaqub, Amber; Prokic, Ivana; Chapuis, Julien; Ahmad, Shahzad; Giedraitis, Vilmantas; Aarsland, Dag; Garcia-Gonzalez, Pablo; Abdelnour, Carla; Alarcón-Martín, Emilio; Alcolea, Daniel; Alegret, Montserrat; Alvarez, Ignacio; Álvarez, Victoria; Armstrong, Nicola J.; Tsolaki, Anthoula; Antúnez, Carmen; Appollonio, Ildebrando; Arcaro, Marina; Archetti, Silvana; Arias Pastor, Alfonso; Arosio, Beatrice; Athanasiu, Lavinia; Bailly, Henri; Banaj, Nerisa; Baquero, Miquel; Barral, Sandra; Beiser, Alexa; Belén Pastor, Ana; Below, Jennifer E.; Benchek, Penelope; Benussi, Luisa; Berr, Claudine; Besse, Céline; Bessi, Valentina; Binetti, Giuliano; Bizarro, Alessandra; Blesa, Rafael; Boada, Mercè; Boerwinkle, Eric; Borroni, Barbara; Boschi, Silvia; Bossù, Paola; Bråthen, Geir; Bressler, Jan; Bresner, Catherine; Brodaty, Henry; Brookes, Keeley J.; Brusco, Luis Ignacio; Buiza-Rueda, Dolores; Bûrger, Katharina; Burholt, Vanessa; Bush, William S.; Calero, Miguel; Cantwell, Laura B.; Chene, Geneviève; Chung, Jaeyoon; Cuccaro, Michael L.; Carracedo, Ángel; Cecchetti, Roberta; Cervera-Carles, Laura; Charbonnier, Camille; Chen, Hung-Hsin; Chillotti, Caterina; Ciccone, Simona; Claassen, Jurgen A. H. R.; Clark, Christopher; Conti, Elisa; Corma-Gómez, Anaïs; Costantini, Emanuele; Custodero, Carlo; Daian, Delphine; Dalmasso, Maria Carolina; Daniele, Antonio; Dardiotis, Efthimios; Dartigues, Jean-François; de Deyn, Peter Paul; de Paiva Lopes, Katia; de Witte, Lot D.; Debette, Stéphanie; Deckert, Jürgen; Del Ser, Teodoro; Denning, Nicola; DeStefano, Anita; Dichgans, Martin; Diehl-Schmid, Janine; Diez-Fairen, Mónica; Dionigi Rossi, Paolo; Djurovic, Srdjan; Duron, Emmanuelle; Düzel, Emrah; Dufouil, Carole; Eiriksdottir, Gudny; Engelborghs, Sebastiaan; Escott-Price, Valentina; Espinosa, Ana; Ewers, Michael; Faber, Kelley M.; Fabrizio, Tagliavini; Fallgaard Nielsen, Sune; Fardo, David W.; Farotti, Lucia; Fenoglio, Chiara; Fernández-Fuertes, Marta; Ferrari, Raffaele; Ferreira, Catarina B.; Ferri, Evelyn; Fin, Bertrand; Fischer, Peter; Fladby, Tormod; Fließbach, Klaus; Fongang, Bernard; Fornage, Myriam; Fortea, Juan; Foroud, Tatiana M.; Fostinelli, Silvia; Fox, Nick C.; Franco-Macías, Emlio; Bullido, María J.; Frank-García, Ana; Froelich, Lutz; Fulton-Howard, Brian; Galimberti, Daniela; García-Alberca, Jose Maria; García-González, Pablo; Garcia-Madrona, Sebastian; Garcia-Ribas, Guillermo; Ghidoni, Roberta; Giegling, Ina; Giorgio, Giaccone; Goate, Alison M.; Goldhardt, Oliver; Gomez-Fonseca, Duber; González-Pérez, Antonio; Graff, Caroline; Grande, Giulia; Green, Emma; Grimmer, Timo; Grünblatt, Edna; Grunin, Michelle; Gudnason, Vilmundur; Guetta-Baranes, Tamar; Haapasalo, Annakaisa; Hadjigeorgiou, Georgios; Haines, Jonathan L.; Hamilton-Nelson, Kara L.; Hampel, Harald; Hanon, Olivier; Hardy, John; Hartmann, Annette M.; Hausner, Lucrezia; Harwood, Janet; Heilmann-Heimbach, Stefanie; Helisalmi, Seppo; Heneka, Michael T.; Hernández, Isabel; Herrmann, Martin J.; Hoffmann, Per; Holmes, Clive; Holstege, Henne; Huerto Vilas, Raquel; Hulsman, Marc; Humphrey, Jack; Jan Biessels, Geert; Jian, Xueqiu; Johansson, Charlotte; Jun, Gyungah R.; Kastumata, Yuriko; Kauwe, John; Kehoe, Patrick G.; Kilander, Lena; Kinhult Ståhlbom, Anne; Kivipelto, Miia; Koivisto, Anne; Kornhuber, Johannes; Kosmidis, Mary H.; Kukull, Walter A.; Kuksa, Pavel P.; Kunkle, Brian W.; Kuzma, Amanda B.; Lage, Carmen; Laukka, Erika J.; Launer, Lenore; Lauria, Alessandra; Lee, Chien-Yueh; Lehtisalo, Jenni; Lerch, Ondrej; Lleó, Alberto; Longstreth, William, Jr.; Lopez, Oscar; Lopez de Munain, Adolfo; Love, Seth; Löwemark, Malin; Luckcuck, Lauren; Lunetta, Kathryn L.; Ma, Yiyi; Macías, Juan; MacLeod, Catherine A.; Maier, Wolfgang; Mangialasche, Francesca; Spallazzi, Marco; Marquié, Marta; Marshall, Rachel; Martin, Eden R.; Martín Montes, Angel; Martínez Rodríguez, Carmen; Masullo, Carlo; Mayeux, Richard; Mead, Simon; Mecocci, Patrizia; Medina, Miguel; Meggy, Alun; Mehrabian, Shima; Mendoza, Silvia; Menéndez-González, Manuel; Mir, Pablo; Moebus, Susanne; Mol, Merel; Molina-Porcel, Laura; Montrreal, Laura; Morelli, Laura; Moreno, Fermin; Morgan, Kevin; Mosley, Thomas; Nöthen, Markus M.; Muchnik, Carolina; Mukherjee, Shubhabrata; Nacmias, Benedetta; Ngandu, Tiia; Nicolas, Gael; Nordestgaard, Børge G.; Olaso, Robert; Orellana, Adelina; Orsini, Michela; Ortega, Gemma; Padovani, Alessandro; Paolo, Caffarra; Papenberg, Goran; Parnetti, Lucilla; Pasquier, Florence; Pastor, Pau; Peloso, Gina; Pérez-Cordón, Alba; Pérez-Tur, Jordi; Pericard, Pierre; Peters, Oliver; Pijnenburg, Yolande A. L.; Pineda, Juan A.; Piñol-Ripoll, Gerard; Pisanu, Claudia; Polak, Thomas; Popp, Julius; Posthuma, Danielle; Priller, Josef; Puerta, Raquel; Quenez, Olivier; Quintela, Inés; Qvist Thomassen, Jesper; Rábano, Alberto; Rainero, Innocenzo; Rajabli, Farid; Ramakers, Inez; Real, Luis M.; Reinders, Marcel J. T.; Reitz, Christiane; Reyes-Dumeyer, Dolly; Ridge, Perry; Riedel-Heller, Steffi; Riederer, Peter; Roberto, Natalia; Rodriguez-Rodriguez, Eloy; Rongve, Arvid; Rosas Allende, Irene; Rosende-Roca, Maitée; Royo, Jose Luis; Rubino, Elisa; Rujescu, Dan; Sáez, María Eugenia; Sakka, Paraskevi; Saltvedt, Ingvild; Sanabria, Ángela; Sánchez-Arjona, María Bernal; Sanchez-Garcia, Florentino; Sánchez Juan, Pascual; Sánchez-Valle, Raquel; Sando, Sigrid B.; Sarnowski, Chloé; Satizabal, Claudia L.; Scamosci, Michela; Scarmeas, Nikolaos; Scarpini, Elio; Scheltens, Philip; Scherbaum, Norbert; Scherer, Martin; Schmid, Matthias; Schneider, Anja; Schott, Jonathan M.; Selbæk, Geir; Seripa, Davide; Serrano, Manuel; Sha, Jin; Shadrin, Alexey A.; Skrobot, Olivia; Slifer, Susan; Snijders, Gijsje J. L.; Soininen, Hilkka; Solfrizzi, Vincenzo; Solomon, Alina; Song, Yeunjoo; Sorbi, Sandro; Sotolongo-Grau, Oscar; Spalletta, Gianfranco; Spottke, Annika; Squassina, Alessio; Stordal, Eystein; Tartan, Juan Pablo; Tárraga, Lluís; Tesí, Niccolo; Thalamuthu, Anbupalam; Thomas, Tegos; Tosto, Giuseppe; Traykov, Latchezar; Tremolizzo, Lucio; Tybjærg-Hansen, Anne; Uitterlinden, Andre; Ullgren, Abbe; Ulstein, Ingun; Valero, Sergi; Valladares, Otto; Van Broeckhoven, Christine; Vance, Jeffery; Vardarajan, Badri N.; van der Lugt, Aad; Van Dongen, Jasper; van Rooij, Jeroen; van Swieten, John; Vandenberghe, Rik; Verhey, Frans; Vidal, Jean-Sébastien; Vogelgsang, Jonathan; Vyhnalek, Martin; Wagner, Michael; Wallon, David; Wang, Li-San; Wang, Ruiqi; Weinhold, Leonie; Wiltfang, Jens; Windle, Gill; Woods, Bob; Yannakoulia, Mary; Zare, Habil; Zhao, Yi; Zhang, Xiaoling; Zhu, Congcong; Zulaica, Miren; EADB; GR@ACE; DEGESCO; EADI; GERAD; Demgene; FinnGen; ADGC; CHARGE; Farrer, Lindsay A.; Psaty, Bruce M.; Ghanbari, Mohsen; Raj, Towfique; Sachdev, Perminder; Mather, Karen; Jessen, Frank; Ikram, M. Arfan; de Mendonça, Alexandre; Hort, Jakub; Tsolaki, Magda; Pericak-Vance, Margaret A.; Amouyel, Philippe; Williams, Julie; Frikke-Schmidt, Ruth; Clarimon, Jordi; Deleuze, Jean-François; Rossi, Giacomina; Seshadri, Sudha; Andreassen, Ole A.; Ingelsson, Martin; Hiltunen, Mikko; Sleegers, Kristel; Schellenberg, Gerard D.; van Duijn, Cornelia M.; Sims, Rebecca; van der Flier, Wiesje M.; Ruiz, Agustín; Ramirez, Alfredo; Lambert, Jean-Charles; Medical and Molecular Genetics, School of Medicine
    Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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    Shared Genetic Risk between Eating Disorder and Substance Use-Related Phenotypes: Evidence from Genome-Wide Association Studies
    (Wiley, 2021) 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; Perica, Vesna Boraska; Buehren, Katharina; Burghardt, Roland; Cassina, Matgteo; 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; Stuber, Garret D.; 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.; 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; 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, Marion 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, Gabrielle; 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.; Mullan Harris, Kathleen; Hesselbrock, Victor; Hewitt, John K.; Hopfer, Christian; 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; Biochemistry and Molecular Biology, School of Medicine
    Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic risk between eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use, mainly abuse and dependence (twin-based genetic correlation [rg]=0.23–0.53). Analytic advances facilitate the computation of genetic correlations using summary statistics from existing genome-wide association studies (GWAS). We investigated shared genetic risk between eating disorder and substance use and disorder phenotypes using GWAS data. Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN 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. Total sample sizes per phenotype ranged from ~2,400 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 non-diagnostic smoking phenotypes (smoking initiation, smoking cessation, and cigarettes per day) and AN without binge-eating (rgs=−0.19 to −0.23; qs<0.04). The observed patterns of association between different eating disorder and substance use-related phenotypes highlights the potentially complex and substance-specific relationships between these behaviors associated with significant public health burden.
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    Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders
    (Springer Nature, 2018-12) 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; Hottenga, Jouke Jan; 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; Wodarz, Norbert; Zill, Peter; Adkins, Daniel E.; Boden, Joseph M.; Boomsma, Dorret I.; 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 M.; Goldman, David; Grucza, Richard A.; Hancock, Dana B.; Harris, Kathleen Mullan; Heath, Andrew C.; Hesselbrock, Victor; Hewitt, John K.; Hopfer, Christian J.; Horwood, John; Iacono, William; Johnson, Eric O.; Kaprio, Jaakko A.; Karpyak, Victor M.; Kendler, Kenneth S.; Kranzler, Henry R.; Krauter, Kenneth; Lichtenstein, Paul; Lind, Penelope A.; McGue, Matt; MacKillop, James; Madden, Pamela A. F.; Maes, Hermine H.; Magnusson, Patrik; Martin, Nicholas G.; Medland, Sarah E.; Montgomery, Grant W.; Nelson, Elliot C.; Nöthen, Markus M.; 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.; Agrawal, Arpana; Biochemistry and Molecular Biology, School of Medicine
    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.