Browsing by Author "Loukola, Anu"

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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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    Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning
    (Springer Nature, 2022) Lahti, Jari; Tuominen, Samuli; Yang, Qiong; Pergola, Giulio; Ahmad, Shahzad; Amin, Najaf; Armstrong, Nicola J.; Beiser, Alexa; Bey, Katharina; Bis, Joshua C.; Boerwinkle, Eric; Bressler, Jan; Campbell, Archie; Campbell, Harry; Chen, Qiang; Corley, Janie; Cox, Simon R.; Davies, Gail; De Jager, Philip L.; Derks, Eske M.; Faul, Jessica D.; Fitzpatrick, Annette L.; Fohner, Alison E.; Ford, Ian; Fornage, Myriam; Gerring, Zachary; Grabe, Hans J.; Grodstein, Francine; Gudnason, Vilmundur; Simonsick, Eleanor; Holliday, Elizabeth G.; Joshi, Peter K.; Kajantie, Eero; Kaprio, Jaakko; Karell, Pauliina; Kleineidam, Luca; Knol, Maria J.; Kochan, Nicole A.; Kwok, John B.; Leber, Markus; Lam, Max; Lee, Teresa; Li, Shuo; Loukola, Anu; Luck, Tobias; Marioni, Riccardo E.; Mather, Karen A.; Medland, Sarah; Mirza, Saira S.; Nalls, Mike A.; Nho, Kwangsik; O'Donnell, Adrienne; Oldmeadow, Christopher; Painter, Jodie; Pattie, Alison; Reppermund, Simone; Risacher, Shannon L.; Rose, Richard J.; Sadashivaiah, Vijay; Scholz, Markus; Satizabal, Claudia L.; Schofield, Peter W.; Schraut, Katharina E.; Scott, Rodney J.; Simino, Jeannette; Smith, Albert V.; Smith, Jennifer A.; Stott, David J.; Surakka, Ida; Teumer, Alexander; Thalamuthu, Anbupalam; Trompet, Stella; Turner, Stephen T.; van der Lee, Sven J.; Villringer, Arno; Völker, Uwe; Wilson, Robert S.; Wittfeld, Katharina; Vuoksimaa, Eero; Xia, Rui; Yaffe, Kristine; Yu, Lei; Zare, Habil; Zhao, Wei; Ames, David; Attia, John; Bennett, David A.; Brodaty, Henry; Chasman, Daniel I.; Goldman, Aaron L.; Hayward, Caroline; Ikram, M. Arfan; Jukema, J. Wouter; Kardia, Sharon L.R.; Lencz, Todd; Loeffler, Markus; Mattay, Venkata S.; Palotie, Aarno; Psaty, Bruce M.; Ramirez, Alfredo; Ridker, Paul M.; Riedel-Heller, Steffi G.; Sachdev, Perminder S.; Saykin, Andrew J.; Scherer, Martin; Schofield, Peter R.; Sidney, Stephen; Starr, John M.; Trollor, Julian; Ulrich, William; Wagner, Michael; Weir, David R.; Wilson, James F.; Wright, Margaret J.; Weinberger, Daniel R.; Debette, Stephanie; Eriksson, Johan G.; Mosley, Thomas H., Jr.; Launer, Lenore J.; van Duijn, Cornelia M.; Deary, Ian J.; Seshadri, Sudha; Räikkönen, Katri; Radiology and Imaging Sciences, School of Medicine
    Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.
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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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    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.