Browsing by Author "Iacono, William G."

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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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    Exome chip meta-analysis fine maps causal variants and elucidates the genetic architecture of rare coding variants in smoking and alcohol use
    (Elsevier, 2018) 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; Medical and Molecular Genetics, School of Medicine
    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 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 152,348-433,216, depending on the phenotype. Rare coding variation explained 1.1-2.2% of phenotypic variance, reflecting 11%-18% of the total SNP 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 3 and 10 variants for 65 loci. 20 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 GWAS loci identifies specific variants contributing to the biological etiology of substance use behavior.
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    A large-scale genome-wide association study meta-analysis of cannabis use disorder
    (Elsevier, 2020-12) Johnson, Emma C.; Demontis, Ditte; Thorgeirsson, Thorgeir E.; Walters, Raymond K.; Polimanti, Renato; Hatoum, Alexander S.; Sanchez-Roige, Sandra; Paul, Sarah E.; Wendt, Frank R.; Clarke, Toni-Kim; Lai, Dongbing; Reginsson, Gunnar W.; Zhou, Hang; He, June; Baranger, David A.A.; Gudbjartsson, Daniel F.; Wedow, Robbee; Adkins, Daniel E.; Adkins, Amy E.; Alexander, Jeffry; Bacanu, Silviu-Alin; Bigdeli, Tim B.; Boden, Joseph; Brown, Sandra A.; Bucholz, Kathleen K.; Bybjerg-Grauholm, Jonas; Corley, Robin P.; Degenhardt, Louisa; Dick, Danielle M.; Domingue, Benjamin W.; Fox, Louis; Goate, Alison M.; Gordon, Scott D.; Hack, Laura M.; Hancock, Dana B.; Hartz, Sarah M.; Hickie, Ian B.; Hougaard, David M.; Krauter, Kenneth; 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.; Sherva, Richard; Silberg, Judy L.; Tarter, Ralph E.; Tyrfingsson, Thorarinn; Wall, Tamara L.; Webb, Bradley T.; Werge, Thomas; Wetherill, Leah; 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.; Mullan Harris, Kathleen; Heath, Andrew C.; Hesselbrock, Victor; Hewitt, John K.; Hopfer, Christian J.; Horwood, John; 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.; Porjesz, Bernice; Riley, Brien P.; Stallings, Michael C.; Vanyukov, Michael M.; Vrieze, Scott; Davis, Lea K.; Bogdan, Ryan; Gelernter, Joel; Edenberg, Howard J.; Stefansson, Kari; Børglum, Anders D.; Agrawal, Arpana; Medical and Molecular Genetics, School of Medicine
    Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50-70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07-1·15, p=1·84 × 10-9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86-0·93, p=6·46 × 10-9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10-21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder.
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    Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
    (Springer Nature, 2019-01-07) 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.; Boer, Rudolf A. de; Leeuw, Christiaan A. de; 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; Leij, Andries R. van der; Meer, Peter van der; 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; Zhao, Wei; Zhou, Kaixin; Amouyel, Philippe; Blankenberg, Stefan; Caulfield, Mark J.; Chowdhury, Rajiv; Cucca, Francesco; Deary, Ian J.; Deloukas, Panos; Angelantonio, Emanuele Di; 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; Harst, Pim van der; 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.; Medical and Molecular Genetics, School of Medicine
    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.
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    Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design
    (Public Library of Science, 2023-06-23) Gross, Rachel; Thaweethai, Tanayott; Rosenzweig, Erika B.; Chan, James; Chibnik, Lori B.; Cicek, Mine S.; Elliott, Amy J.; Flaherman, Valerie J.; Foulkes, Andrea S.; Witvliet, Margot Gage; Gallagher, Richard; Gennaro, Maria Laura; Jernigan, Terry L.; Karlson, Elizabeth W.; Katz, Stuart D.; Kinser, Patricia A.; Kleinman, Lawrence C.; Lamendola-Essel, Michelle F.; Milner, Joshua D.; Mohandas, Sindhu; Mudumbi, Praveen C.; Newburger, Jane W.; Rhee, Kyung E.; Salisbury, Amy L.; Snowden, Jessica N.; Stein, Cheryl R.; Stockwell, Melissa S.; Tantisira, Kelan G.; Thomason, Moriah E.; Truong, Dongngan T.; Warburton, David; Wood, John C.; Ahmed, Shifa; Akerlundh, Almary; Alshawabkeh, Akram N.; Anderson, Brett R.; Aschner, Judy L.; Atz, Andrew M.; Aupperle, Robin L.; Baker, Fiona C.; Balaraman, Venkataraman; Banerjee, Dithi; Barch, Deanna M.; Baskin-Sommers, Arielle; Bhuiyan, Sultana; Bind, Marie-Abele C.; Bogie, Amanda L.; Buchbinder, Natalie C.; Bueler, Elliott; Bükülmez, Hülya; Casey, B. J.; Chang, Linda; Clark, Duncan B.; Clifton, Rebecca G.; Clouser, Katharine N.; Cottrell, Lesley; Cowan, Kelly; D'Sa, Viren; Dapretto, Mirella; Dasgupta, Soham; Dehority, Walter; Dummer, Kirsten B.; Elias, Matthew D.; Esquenazi-Karonika, Shari; Evans, Danielle N.; Faustino, E. Vincent S.; Fiks, Alexander G.; Forsha, Daniel; Foxe, John J.; Friedman, Naomi P.; Fry, Greta; Gaur, Sunanda; Gee, Dylan G.; Gray, Kevin M.; Harahsheh, Ashraf S.; Heath, Andrew C.; Heitzeg, Mary M.; Hester, Christina M.; Hill, Sophia; Hobart-Porter, Laura; Hong, Travis K. F.; Horowitz, Carol R.; Hsia, Daniel S.; Huentelman, Matthew; Hummel, Kathy D.; Iacono, William G.; Irby, Katherine; Jacobus, Joanna; Jacoby, Vanessa L.; Jone, Pei-Ni; Kaelber, David C.; Kasmarcak, Tyler J.; Kluko, Matthew J.; Kosut, Jessica S.; Laird, Angela R.; Landeo-Gutierrez, Jeremy; Lang, Sean M.; Larson, Christine L.; Lim, Peter Paul C.; Lisdahl, Krista M.; McCrindle, Brian W.; McCulloh, Russell J.; Mendelsohn, Alan L.; Metz, Torri D.; Morgan, Lerraughn M.; Müller-Oehring, Eva M.; Nahin, Erica R.; Neale, Michael C.; Ness-Cochinwala, Manette; Nolan, Sheila M.; Oliveira, Carlos R.; Oster, Matthew E.; Payne, R. Mark; Raissy, Hengameh; Randall, Isabelle G.; Rao, Suchitra; Reeder, Harrison T.; Rosas, Johana M.; Russell, Mark W.; Sabati, Arash A.; Sanil, Yamuna; Sato, Alice I.; Schechter, Michael S.; Selvarangan, Rangaraj; Shakti, Divya; Sharma, Kavita; Squeglia, Lindsay M.; Stevenson, Michelle D.; Szmuszkovicz, Jacqueline; Talavera-Barber, Maria M.; Teufel, Ronald J., II; Thacker, Deepika; Udosen, Mmekom M.; Warner, Megan R.; Watson, Sara E.; Werzberger, Alan; Weyer, Jordan C.; Wood, Marion J.; Yin, H. Shonna; Zempsky, William T.; Zimmerman, Emily; Dreyer, Benard P.; Pediatrics, School of Medicine
    Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.
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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.