Browsing by Author "Kaprio, Jaakko A."

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    Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits
    (medRxiv, 2025-02-03) Johnson, Emma C.; Lai, Dongbing; Miller, Alex P.; Hatoum, Alexander S.; Deak, Joseph D.; Balbona, Jared V.; Baranger, David A. A.; Galimberti, Marco; Sanichwankul, Kittipong; Thorgeirsson, Thorgeir; McColbert, Sarah; Sanchez-Roige, Sandra; Adhikari, Keyrun; Docherty, Anna; Degenhardt, Louisa; Edwards, Tobias; Fox, Louis; Giannelis, Alexandros; Jeffries, Paul; Korhonen, Tellervo; Morrison, Claire; Nunez, Yaira Z.; Palviainen, Teemu; Su, Mei-Hsin; Romero Villela, Pamela N.; Wetherill, Leah; Willoughby, Emily A.; Zellers, Stephanie; Bierut, Laura; Buchwald, Jadwiga; Copeland, William; Corley, Robin; Friedman, Naomi P.; Foroud, Tatiana M.; Gillespie, Nathan A.; Gizer, Ian R.; Heath, Andrew C.; Hickie, Ian B.; Kaprio, Jaakko A.; Keller, Matthew C.; Lee, James L.; Lind, Penelope A.; Madden, Pamela A.; Maes, Hermine H. M.; Martin, Nicholas G.; McGue, Matt; Medland, Sarah E.; Nelson, Elliot C.; Pearson, John V.; Porjesz, Bernice; Stallings, Michael; Vrieze, Scott; Wilhelmsen, Kirk C.; Walters, Raymond K.; Polimanti, Renato; Malison, Robert T.; Zhou, Hang; Stefansson, Kari; Potenza, Marc N.; Mutirangura, Apiwat; Shotelersuk, Vorasuk; Kalayasiri, Rasmon; Edenberg, Howard J.; Gelernter, Joel; Agrawal, Arpana; Medical and Molecular Genetics, School of Medicine
    Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement. We conducted a genome-wide association study of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry, 10,231 of African ancestry, 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes. We replicated the well-known association at the CHRNA5 locus (lead SNP: rs147144681, p =1.27E-11 in European ancestry; lead SNP = rs2036527, p = 6.49e-13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder and 6 of 11 individual diagnostic criteria, but none of the Fagerström Test for Nicotine Dependence (FTND) items, in the independent NESARC-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than did a "problematic tobacco use" factor (a combination of cigarettes per day and nicotine dependence defined by the FTND). Finally, DSM-NicDep was strongly genetically correlated with a GWAS of tobacco use disorder as defined in electronic health records, suggesting that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.
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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.