Musliner, Katherine L., Mortensen, Preben B., McGrath, John J., Suppli, Nis P., Hougaard, David M., Bybjerg-Grauholm, Jonas ORCID: 0000-0003-1705-4008, Baekvad-Hansen, Marie, Andreassen, Ole, Pedersen, Carsten B., Pedersen, Marianne G., Mors, Ole, Nordentoft, Merete ORCID: 0000-0003-4895-7023, Borglum, Anders D., Werge, Thomas, Agerbo, Esben ORCID: 0000-0002-2849-524X, Stahl, Eli A., Breen, Gerome, Forstner, Andreas J., McQuillin, Andrew ORCID: 0000-0003-1567-2240, Ripke, Stephan, Trubetskoy, Vassily, Mattheisen, Manuel ORCID: 0000-0002-8442-493X, Wang, Yunpeng, Coleman, Jonathan R., I, Gaspar, Helena A., de Leeuw, Christiaan A., Steinberg, Stacy, Pavlides, Jennifer M. Whitehead, Trzaskowski, Maciej, Pers, Tune H., Holmans, Peter A., Abbott, Liam, Agerbo, Esben ORCID: 0000-0002-2849-524X, Akil, Huda, Albani, Diego, Alliey-Rodriguez, Ney, Als, Thomas D., Anjorin, Adebayo, Antilla, Verneri, Awasthi, Swapnil, Badner, Judith A., Etzekvad-Hansen, Marie, Barchas, Jack D., Bass, Nicholas, Bauer, Michael, Belliveau, Richard, Bergen, Sarah E., Pedersen, Carsten Bocker, Boen, Erlend, Boks, Marco, Boocock, James, Budde, Monika, Bunney, William, Burmeister, Margit, Bybjerg-Grauholm, Jonas ORCID: 0000-0003-1705-4008, Byerley, William, Casas, Miguel, Cerrato, Felecia, Cervantes, Pablo, Chambert, Kimberly, Chamey, Alexander W., Chen, Danfeng, Churchhouse, Claire, Clarke, Toni-Kim ORCID: 0000-0002-7745-6351, Coryell, William, Craig, David W., Cruceanu, Cristiana, Curtis, David, Czerski, Piotr M., Dale, Anders M., de Jong, Simone, Degenhardt, Franziska, Del-Favero, Jurgen, DePaulo, J. Raymond, Djurovic, Srdjan, Dobbyn, Amanda L., Dumont, Ashley, Elvsashagen, Torbjorn, Escott-Price, Valentina, Fan, Chun Chieh, Fischer, Sascha B., Flickinger, Matthew, Foroud, Tatiana M., Forty, Liz, Frank, Josef, Fraser, Christine, Freimer, Nelson B., Frisen, Louise, Gade, Katrin, Gage, Diane, Garnham, Julie, Giambartobmei, Claudia, Pedersen, Marianne Giortz, Goldstein, Jaqueline, Gordon, Scott D., Gordon-Smith, Katherine, Green, Elaine K., Green, Melissa J., Greenwood, Tiffany A., Grove, Jakob ORCID: 0000-0003-2284-5744, Guan, Weihua, Parra, Jose Guzman, Hamshere, Marian L., Hautzinger, Martin, Heilbronner, Urs, Herms, Stefan, Hipolito, Maria, Hoffmann, Per, Holland, Dominic, Huckins, Laura, Jamain, Stephan, Johnson, Jessica S., Jureus, Anders, Kandaswamy, Radhika, Karlsson, Robert, Kennedy, James L., Kittel-Schneider, Sarah, Knott, Sarah, V, Knowles, James A., Kogevinas, Manolis, Koller, Anna C., Kupka, Ralph, Lavebratt, Catharina, Lawrence, Jacob, Lawson, William B., Leber, Markus, Lee, Phil H., Levy, Shawn E., Li, Jun Z., Liu, Chunyu, Lucae, Susanne, Maaser, Anna, MacIntyre, Donald J., Mahon, Pamela B., Maier, Wolfgang, Martinsson, Lina ORCID: 0000-0002-2938-2773, McCarroll, Steve, McGuffin, Peter, McInnis, Melvin G., McKay, James D., Medeiros, Helena, Medland, Sarah E., Meng, Fan, Milani, Lili, Montgomery, Grant W., Morris, Derek W., Muehleisen, Thomas W., Mullins, Niamh, Nguyen, Hoang, Nievergelt, Caroline M., Adolfsson, Annelie Nordin, Nwulia, Evaristus A., O'Donovan, Claire, Loohuis, Loes M. Olde, Ori, Anil P. S., Oruc, Lilijana, Osby, Urban, Perlis, Roy H., Perry, Amy, Pfennig, Andrea, Potash, James B., Purcell, Shaun M., Regeer, Eline J., Reif, Andreas, Reinbold, Celine S., Rice, John P., Rivas, Fabio, Rivera, Margarita ORCID: 0000-0003-4717-1045, Roussos, Panos, Ruderfer, Douglas M., Ryu, Euijung, Sanchez-Mora, Cristina, Schatzberg, Alan F., Scheftner, William A., Schork, Nicholas J., Weickert, Cynthia Shannon, Shehktman, Tatyana, Shilling, Paul D., Sigurdsson, Engilbert, Slaney, Claire, Smeland, Olav B., Sobell, Janet L., Hansen, Christine Soholm, Spijker, Anne T., St Clair, David, Steffens, Michael, Strauss, John S., Streit, Fabian, Strohmaier, Jana, Szelinger, Szabolcs, Thompson, Robert C., Thorgeirsson, Thorgeir E., Treutlein, Jens, Vedder, Helmut, Wang, Weiqing, Watson, Stanley J., Weickert, Thomas W., Witt, Stephanie H., Xi, Simon, Xu, Wei, Young, Allan H., Zandi, Peter, Zhang, Peng, Zollner, Sebastian, Agartz, Ingrid, Aida, Martin, Backlund, Lena, Baune, Bernhard T., Bellivier, Frank, Berrettini, Wade H., Biemacka, Joanna M., Blackwood, Douglas H. R., Boehnke, Michael, Berglum, Anders D., Corvin, Aiden, Craddock, Nicholas, Daly, Mark J., Dannlowski, Udo, Esko, Tonu, Etain, Bruno ORCID: 0000-0002-5377-1488, Frye, Mark, Fullerton, Janice M., Gershon, Elliot S., Goes, Fernando, Grigoroiu-Serbanescu, Maria ORCID: 0000-0002-1304-6687, Hauser, Joanna, Hougaard, David M., Hultman, Christina M., Jones, Ian, Jones, Lisa A., Kahn, Rene S., Kirov, George, Landen, Mikael, Leboyer, Marion, Lewis, Cathryn M., Li, Qingqin S., Lissowska, Jolanta ORCID: 0000-0003-2695-5799, Martin, Nicholas G., Mayoral, Fermin, McElroy, Susan L., McIntosh, Andrew M., McMahon, Francis J., Melle, Ingrid, Metspalu, Andres, Mitchell, Philip B., Morken, Gunnar, Mors, Ole, Mortensen, Preben Bo, Mueller-Myhsok, Bertram, Myers, Richard M., Neale, Benjamin M., Nimgaonkar, Vishwajit, Nordentoft, Merete ORCID: 0000-0003-4895-7023, Noethen, Markus M., O'Donovan, Michael C., Oedegaard, Ketil J., Owen, Michael, Paciga, Sara A., Pato, Carlos, Pato, Michele T., Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Ribases, Marta ORCID: 0000-0003-1039-1116, Rietschel, Marcella, Rouleau, Guy A., Schalling, Martin, Schofield, Peter R., Schulze, Thomas G., Serretti, Alessandro ORCID: 0000-0003-4363-3759, Smoller, Jordan W., Stefansson, Hreinn, Stefansson, Kari, Stordal, Eystein, Sullivan, Patrick F., Turecki, Gustavo, Vaaler, Arne E., Ieta, Eduard, V, Vincent, John B., Werge, Thomas, Nurnberger, John, I, Wray, Naomi R., Di Florio, Arianna, Edenberg, Howard J., Cichon, Sven, Ophoff, Roel A., Scott, Laura J., Andreassen, Ole A., Kelsoe, John and Sklar, Pamela (2019). Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population. JAMA Psychiatry, 76 (5). S. 516 - 526. CHICAGO: AMER MEDICAL ASSOC. ISSN 2168-6238

Full text not available from this repository.

Abstract

IMPORTANCE Although the usefulness of polygenic risk scores as a measure of genetic liability for major depression (MD) has been established, their association with depression in the general population remains relatively unexplored. OBJECTIVE To evaluate whether polygenic risk scores for MD, bipolar disorder (BD), and schizophrenia (SZ) are associated with depression in the general population and explore whether these polygenic liabilities are associated with heterogeneity in terms of age at onset and severity at the initial depression diagnosis. DESIGN SETTING AND PARTICIPANTS Participants were drawn from the Danish iPSYCH2012 case-cohort study, a representative sample drawn from the population of Denmark born between May 1, 1981, and December 31, 2005. The hazard of depression was estimated using Cox regressions modified to accommodate the case-cohort design. Case-only analyses were conducted using linear and multinomial regressions. The data analysis was conducted from February 2017 to June 2018. EXPOSURES Polygenic risk scores for MD, BD, and SZ trained using the most recent genome-wide association study results from the Psychiatric Genomics Consortium. MAIN OUTCOMES AND MEASURES The main outcome was first depressive episode (international Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code F32) treated in hospital-based psychiatric care. Severity at the initial diagnosis was measured using the ICD-10 code severity specifications (mild, moderate, severe without psychosis, and severe with psychosis) and treatment setting (inpatient, outpatient, and emergency). RESULTS Of 34 573 participants aged 10 to 31 years at censoring, 68% of those with depression were female compared with 48.9% of participants without depression. Each SD increase in polygenic liability for MD, BD, and SZ was associated with 30% (hazard ratio [HR], 1.30; 95% CI, 1.27-1.33), 5% (HR, 1.05; 95% CI, 1.02-1.07), and 12% (HR, 1.12; 95% CI, 1.09-1.15) increases in the hazard of depression, respectively. Among cases, a higher polygenic liability for BD was associated with earlier depression onset (beta =-.07; SE =.02; P =.002). CONCLUSIONS AND RELEVANCE Polygenic ability for MD is associated with first depress on in the general population, which supports the idea that these scores tap into an underlying liability for developing the disorder. The fact that polygenic risk for BD and polygenic risk for SZ also were associated with depression is consistent with prior evidence that these disorders share some common genetic overlap. Variations in polygenic liability may contribute slightly to heterogeneity in clinical presentation, but these associations appear minimal.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Musliner, Katherine L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mortensen, Preben B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGrath, John J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suppli, Nis P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hougaard, David M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bybjerg-Grauholm, JonasUNSPECIFIEDorcid.org/0000-0003-1705-4008UNSPECIFIED
Baekvad-Hansen, MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andreassen, OleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pedersen, Carsten B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pedersen, Marianne G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mors, OleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nordentoft, MereteUNSPECIFIEDorcid.org/0000-0003-4895-7023UNSPECIFIED
Borglum, Anders D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Werge, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Stahl, Eli A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Trubetskoy, VassilyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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de Leeuw, Christiaan A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Pers, Tune H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Anjorin, AdebayoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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O'Donovan, Michael C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oedegaard, Ketil J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Owen, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paciga, Sara A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pato, CarlosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pato, Michele T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Posthuma, DanielleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramos-Quiroga, Josep AntoniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ribases, MartaUNSPECIFIEDorcid.org/0000-0003-1039-1116UNSPECIFIED
Rietschel, MarcellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rouleau, Guy A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schalling, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schofield, Peter R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulze, Thomas G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Serretti, AlessandroUNSPECIFIEDorcid.org/0000-0003-4363-3759UNSPECIFIED
Smoller, Jordan W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stefansson, HreinnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stefansson, KariUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stordal, EysteinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sullivan, Patrick F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Turecki, GustavoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vaaler, Arne E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ieta, Eduard, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vincent, John B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Werge, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nurnberger, John, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wray, Naomi R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Di Florio, AriannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Edenberg, Howard J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cichon, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ophoff, Roel A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scott, Laura J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andreassen, Ole A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kelsoe, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sklar, PamelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-149619
DOI: 10.1001/jamapsychiatry.2018.4166
Journal or Publication Title: JAMA Psychiatry
Volume: 76
Number: 5
Page Range: S. 516 - 526
Date: 2019
Publisher: AMER MEDICAL ASSOC
Place of Publication: CHICAGO
ISSN: 2168-6238
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PsychiatryMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14961

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