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101. Bilateral oophorectomy and rate of colorectal cancer: A prospective cohort study

Author

Koch, Trine, primary, Therming Jørgensen, Jeanette, additional, Christensen, Jane, additional, Duun‐Henriksen, Anne Katrine, additional, Priskorn, Lærke, additional, Kildevæld Simonsen, Mette, additional, Dehlendorff, Christian, additional, Jovanovic Andersen, Zorana, additional, Juul, Anders, additional, Bräuner, Elvira V., additional, and Hickey, Martha, additional

Published
2021
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104. Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

Author

Andlauer, Till F M, Guzman-Parra, Jose, Orozco Diaz, Guillermo, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Gage, Diane, Garnham, Julie, Giambartolomei, Claudia, Pedersen, Marianne Giørtz, Goldstein, Jaqueline, Gordon, Scott D, Gordon-Smith, Katherine, de Diego-Otero, Yolanda, Green, Elaine K, Green, Melissa J, Greenwood, Tiffany A, Grove, Jakob, Guan, Weihua, Parra, José Guzman, Hamshere, Marian L, Hautzinger, Martin, Heilbronner, Urs, Herms, Stefan, Moreno-Küstner, Berta, Hipolito, Maria, Hoffmann, Per, Holland, Dominic, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, Juréus, Anders, Kandaswamy, Radhika, Karlsson, Robert, Kennedy, James L, Auburger, Georg, Kittel-Schneider, Sarah, Knowles, James A, Kogevinas, Manolis, Koller, Anna C, Kupka, Ralph, Lavebratt, Catharina, Lawrence, Jacob, Lawson, William B, Leber, Markus, Lee, Phil H, Degenhardt, Franziska, Levy, Shawn E, Li, Jun Z, Liu, Chunyu, Lucae, Susanne, Maaser, Anna, MacIntyre, Donald J, Mahon, Pamela B, Maier, Wolfgang, Martinsson, Lina, McCarroll, Steve, Heilmann-Heimbach, Stefanie, McGuffin, Peter, McInnis, Melvin G, McKay, James D, Medeiros, Helena, Medland, Sarah E, Meng, Fan, Milani, Lili, Montgomery, Grant W, Morris, Derek W, Mühleisen, 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, Ösby, Urban, Perlis, Roy H, Perry, Amy, Pfennig, Andrea, Potash, James B, Purcell, Shaun M, Regeer, Eline J, Reif, Andreas, Reinbold, Céline S, Rice, John P, Richards, Alexander L, Frank, Josef, Rivas, Fabio, Rivera, Margarita, Roussos, Panos, Ruderfer, Douglas M, Ryu, Euijung, Sánchez-Mora, Cristina, Schatzberg, Alan F, Scheftner, William A, Schork, Nicholas J, Weickert, Cynthia Shannon, Foo, Jerome C, Shehktman, Tatyana, Shilling, Paul D, Sigurdsson, Engilbert, Slaney, Claire, Smeland, Olav B, Sobell, Janet L, Hansen, Christine Søholm, Spijker, Anne T, Clair, David St, Steffens, Michael, Streit, Fabian, Treutlein, Jens, Strauss, John S, Strohmaier, Jana, Szelinger, Szabolcs, Thompson, Robert C, EThorgeirsson, Thorgeir, Vedde, Helmut, Wang, Weiqing, Watson, Stanley J, Witt, Stephanie H, Weickert, Thomas W, Xi, Simon, Xu, Wei, Young, Allan H, Zandi, Peter, Zhang, Peng, Zollner, Sebastian, Adolfsson, Rolf, Agartz, Ingrid, Cichon, Sven, Alda, Martin, Backlund, Lena, Baune, Bernhard T, Bellivier, Frank, Berrettini, Wade H, Biernacka, Joanna M, Blackwood, Douglas H R, Boehnke, Michael, Børglum, Anders D, Corvin, Aiden, Craddock, Nicholas, Daly, Mark J, Dannlowski, Udo, Esko, Tõnu, Etain, Bruno, Frye, Mark, Fullerton, Janice M, Gershon, Elliot S, Gill, Michael, Goes, Fernando, Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Hougaard, David M, Hultman, Christina M, Jones, Ian, Jones, Lisa A, Kahn, René S, Kirov, George, Landén, Mikael, Leboyer, Marion, Mayoral, Fermín, Lewis, Cathryn M, Li, Qingqin S, Lissowska, Jolanta, Martin, Nicholas G, Mayoral, Fermin, McElroy, Susan L, McIntosh, Andrew M, McMahon, Francis J, Melle, Ingrid, Metspalu, Andres, Müller-Myhsok, Bertram, Mitchell, Philip B, Morken, Gunnar, Mors, Ole, Mortensen, Preben Bo, Myers, Richard M, Neale, Benjamin M, Nimgaonkar, Vishwajit, Nordentoft, Merete, Nöthen, Markus M, Forstner, Andreas J, O'Donovan, Michael C, Oedegaard, Ketil J, Owen, Michael J, Paciga, Sara A, Pato, Carlos, Pato, Michele T, Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Ribasés, Marta, Rietschel, Marcella, Rouleau, Guy A, Schalling, Martin, Schofield, Peter R, Schulze, Thomas G, Serretti, Alessandro, Smoller, Jordan W, Stefansson, Hreinn, Stefansson, Kari, Stordal, Eystein, Sullivan, Patrick F, Turecki, Gustavo, Vaaler, Arne E, Vieta, Eduard, Vincent, John B, Werge, Thomas, Nurnberger, John I, Wray, Naomi R, Florio, Arianna Di, Edenberg, Howard J, Stahl, Eli A, Ophoff, Roel A, Scott, Laura J, Andreassen, Ole A, Kelsoe, John, Sklar, Pamela, Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M, Breen, Gerome, Abdellaoui, Abdel, Adams, Mark J, Agerbo, Esben, Air, Tracy M, Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T F, Bigdeli, Tim B, Binder, Elisabeth B, Bryois, Julien, Buttenschøn, Henriette N, Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R I, Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, McQuillin, Andrew, Craddock, Nick, Crawford, Gregory E, Davies, Gail, Deary, Ian J, Derks, Eske M, Direk, Nese, Dolan, Conor V, Dunn, Erin C, Eley, Thalia C, Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K, Gaspar, Héléna A, Goes, Fernando S, Trubetskoy, Vassily, Hall, Lynsey S, Hansen, Thomas F, Hickie, Ian B, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Howard, David M, Ising, Marcus, Jansen, Rick, Jorgenson, Eric, Kohane, Isaac S, Kraft, Julia, Wang, Yunpeng, Kretzschmar, Warren W, Kutalik, Zoltán, Li, Yihan, Lind, Penelope A, MacKinnon, Dean F, Maier, Robert M, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, Mehta, Divya, Middeldorp, Christel M, Mihailov, Evelin, Milaneschi, Yuri, Mondimore, Francis M, Mostafavi, Sara, Nauck, Matthias, Ng, Bernard, Nivard, Michel G, Nyholt, Dale R, O'Reilly, Paul F, Oskarsson, Hogni, Painter, Jodie N, González, Maria José, de Leeuw, Christiaan A, Pedersen, Carsten Bøcker, Peterson, Roseann E, Pettersson, Erik, Peyrot, Wouter J, Pistis, Giorgio, Quiroz, Jorge A, Qvist, Per, Steinberg, Stacy, Riley, Brien P, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C, Shen, Ling, Shi, Jianxin, Shyn, Stanley I, Sinnamon, Grant C B, Pavlides, Jennifer M Whitehead, Smit, Johannes H, Smith, Daniel J, Tansey, Katherine E, Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A, Thorgeirsson, Thorgeir E, Traylor, Matthew, Uitterlinden, André G, Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M, Viktorin, Alexander, Pers, Tune H, Visscher, Peter M, Webb, Bradley T, Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Wu, Yang, Xi, Hualin S, Yang, Jian, Holmans, Peter A, Zhang, Futao, Arolt, Volker, Berger, Klaus, Boomsma, Dorret I, de Geus, E. J. C., DePaulo, J Raymond, Domenici, Enrico, Abbott, Liam, Domschke, Katharina, Grabe, Hans J, Hamilton, Steven P, Hayward, Caroline, Heath, Andrew C, Kendler, Kenneth S, Kloiber, Stefan, Lewis, Glyn, Madden, Pamela A F, Magnusson, Patrik K, Akil, Huda, Pedersen, Nancy L, Penninx, Brenda W J H, Porteous, David J, Preisig, Martin, Albani, Diego, Schaefer, Catherine, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M, Gil Flores, Susana, Alliey-Rodriguez, Ney, Levinson, Douglas F, Als, Thomas D, Anjorin, Adebayo, Antilla, Verneri, Awasthi, Swapnil, Badner, Judith A, Barchas, Jack D, Bass, Nicholas, Bauer, Michael, Cabaleiro Fabeiro, Francisco J, Belliveau, Richard, Bergen, Sarah E, Bøen, Erlend, Boks, Marco, Boocock, James, Budde, Monika, Bunney, William, Burmeister, Margit, Del Río Noriega, Francisco, Byerley, William, Casas, Miquel, Cerrato, Felecia, Cervantes, Pablo, Chambert, Kimberly, Charney, Alexander W, Chen, Danfeng, Churchhouse, Claire, Coryell, William, Perez, Fermin Perez, Craig, David W, Cruceanu, Cristiana, Czerski, Piotr M, Dale, Anders M, de Jong, Simone, Del-Favero, Jurgen, Djurovic, Srdjan, Dobbyn, Amanda L, Haro González, Jesus, Dumont, Ashley, Elvsåshagen, Torbjørn, Fan, Chun Chieh, Fischer, Sascha B, Flickinger, Matthew, Foroud, Tatiana M, Forty, Liz, Fraser, Christine, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, Epidemiology and Data Science, APH - Digital Health, Andlauer T.F.M., Guzman-Parra J., Streit F., Strohmaier J., Gonzalez M.J., Gil Flores S., Cabaleiro Fabeiro F.J., del Rio Noriega F., Perez F.P., Haro Gonzalez J., Orozco Diaz G., de Diego-Otero Y., Moreno-Kustner B., Auburger G., Degenhardt F., Heilmann-Heimbach S., Herms S., Hoffmann P., Frank J., Foo J.C., Treutlein J., Witt S.H., Cichon S., Kogevinas M., Stahl E.A., Breen G., Forstner A.J., McQuillin A., Ripke S., Trubetskoy V., Mattheisen M., Wang Y., Coleman J.R.I., Gaspar H.A., de Leeuw C.A., Steinberg S., Pavlides J.M.W., Trzaskowski M., Pers T.H., Holmans P.A., Abbott L., Agerbo E., Akil H., Albani D., Alliey-Rodriguez N., Als T.D., Anjorin A., Antilla V., Awasthi S., Badner J.A., Baekvad-Hansen M., Barchas J.D., Bass N., Bauer M., Belliveau R., Bergen S.E., Pedersen C.B., Boen E., Boks M., Boocock J., Budde M., Bunney W., Burmeister M., Bybjerg-Grauholm J., Byerley W., Casas M., Cerrato F., Cervantes P., Chambert K., Charney A.W., Chen D., Churchhouse C., Clarke T.-K., Coryell W., Craig D.W., Cruceanu C., Czerski P.M., Dale A.M., de Jong S., Del-Favero J., DePaulo J.R., Djurovic S., Dobbyn A.L., Dumont A., Elvsashagen T., Escott-Price V., Fan C.C., Fischer S.B., Flickinger M., Foroud T.M., Forty L., Fraser C., Freimer N.B., Frisen L., Gade K., Gage D., Garnham J., Giambartolomei C., Pedersen M.G., Goldstein J., Gordon S.D., Gordon-Smith K., Green E.K., Green M.J., Greenwood T.A., Grove J., Guan W., Parra J.G., Hamshere M.L., Hautzinger M., Heilbronner U., Hipolito M., Holland D., Huckins L., Jamain S., Johnson J.S., Jureus A., Kandaswamy R., Karlsson R., Kennedy J.L., Kittel-Schneider S., Knowles J.A., Koller A.C., Kupka R., Lavebratt C., Lawrence J., Lawson W.B., Leber M., Lee P.H., Levy S.E., Li J.Z., Liu C., Lucae S., Maaser A., MacIntyre D.J., Mahon P.B., Maier W., Martinsson L., McCarroll S., McGuffin P., McInnis M.G., McKay J.D., Medeiros H., Medland S.E., Meng F., Milani L., Montgomery G.W., Morris D.W., Muhleisen T.W., Mullins N., Nguyen H., Nievergelt C.M., Adolfsson A.N., Nwulia E.A., O'Donovan C., Loohuis L.M.O., Ori A.P.S., Oruc L., Osby U., Perlis R.H., Perry A., Pfennig A., Potash J.B., Purcell S.M., Regeer E.J., Reif A., Reinbold C.S., Rice J.P., Richards A.L., Rivas F., Rivera M., Roussos P., Ruderfer D.M., Ryu E., Sanchez-Mora C., Schatzberg A.F., Scheftner W.A., Schork N.J., Weickert C.S., Shehktman T., Shilling P.D., Sigurdsson E., Slaney C., Smeland O.B., Sobell J.L., Hansen C.S., Spijker A.T., Clair D.S., Steffens M., Strauss J.S., Szelinger S., Thompson R.C., EThorgeirsson T., Vedde H., Wang W., Watson S.J., Weickert T.W., Xi S., Xu W., Young A.H., Zandi P., Zhang P., Zollner S., Adolfsson R., Agartz I., Alda M., Backlund L., Baune B.T., Bellivier F., Berrettini W.H., Biernacka J.M., Blackwood D.H.R., Boehnke M., Borglum A.D., Corvin A., Craddock N., Daly M.J., Dannlowski U., Esko T., Etain B., Frye M., Fullerton J.M., Gershon E.S., Gill M., Goes F., Grigoroiu-Serbanescu M., Hauser J., Hougaard D.M., Hultman C.M., Jones I., Jones L.A., Kahn R.S., Kirov G., Landen M., Leboyer M., Lewis C.M., Li Q.S., Lissowska J., Martin N.G., Mayoral F., McElroy S.L., McIntosh A.M., McMahon F.J., Melle I., Metspalu A., Mitchell P.B., Morken G., Mors O., Mortensen P.B., Muller-Myhsok B., Myers R.M., Neale B.M., Nimgaonkar V., Nordentoft M., Nothen M.M., O'Donovan M.C., Oedegaard K.J., Owen M.J., Paciga S.A., Pato C., Pato M.T., Posthuma D., Ramos-Quiroga J.A., Ribases M., Rietschel M., Rouleau G.A., Schalling M., Schofield P.R., Schulze T.G., Serretti A., Smoller J.W., Stefansson H., Stefansson K., Stordal E., Sullivan P.F., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Werge T., Nurnberger J.I., Wray N.R., Florio A.D., Edenberg H.J., Ophoff R.A., Scott L.J., Andreassen O.A., Kelsoe J., Sklar P., Byrne E.M., Abdellaoui A., Adams M.J., Air T.M., Bacanu S.-A., Beekman A.T.F., Bigdeli T.B., Binder E.B., Bryois J., Buttenschon H.N., Cai N., Castelao E., Christensen J.H., Colodro-Conde L., Couvy-Duchesne B., Crawford G.E., Davies G., Deary I.J., Derks E.M., Direk N., Dolan C.V., Dunn E.C., Eley T.C., Kiadeh F.F.H., Finucane H.K., Goes F.S., Hall L.S., Hansen T.F., Hickie I.B., Homuth G., Horn C., Hottenga J.-J., Howard D.M., Ising M., Jansen R., Jorgenson E., Kohane I.S., Hill, Kraft J., Kretzschmar W.W., Kutalik Z., Li Y., Lind P.A., MacKinnon D.F., Maier R.M., Marchini J., Mbarek H., McGrath P., Mehta D., Middeldorp C.M., Mihailov E., Milaneschi Y., Mondimore F.M., Mostafavi S., Nauck M., Ng B., Nivard M.G., Nyholt D.R., O'Reilly P.F., Oskarsson H., Painter J.N., Peterson R.E., Pettersson E., Peyrot W.J., Pistis G., Quiroz J.A., Qvist P., Riley B.P., Mirza S.S., Schoevers R., Schulte E.C., Shen L., Shi J., Shyn S.I., Sinnamon G.C.B., Smit J.H., Smith D.J., Tansey K.E., Teismann H., Teumer A., Thompson W., Thomson P.A., Thorgeirsson T.E., Traylor M., Uitterlinden A.G., Umbricht D., Van der Auwera S., van Hemert A.M., Viktorin A., Visscher P.M., Webb B.T., Weinsheimer S.M., Wellmann J., Willemsen G., Wu Y., Xi H.S., Yang J., Zhang F., Arolt V., Berger K., Boomsma D.I., de Geus E.J.C., Domenici E., Domschke K., Grabe H.J., Hamilton S.P., Hayward C., Heath A.C., Kendler K.S., Kloiber S., Lewis G., Madden P.A.F., Magnusson P.K., Pedersen N.L., Penninx B.W.J.H., Porteous D.J., Preisig M., Schaefer C., Tiemeier H., Uher R., Volzke H., Weissman M.M., Levinson D.F., Child and Adolescent Psychiatry / Psychology, Epidemiology, Internal Medicine, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, APH - Methodology, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Complex Trait Genetics, and Adult Psychiatry

Subjects
Netherlands Twin Register (NTR), Genetic variants, Bipolar Disorder, Specific risk, Disease, 0302 clinical medicine, Multiplex, Genetic risk, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Depression (differential diagnoses), 0303 health sciences, Depression, ddc, 3. Good health, Geðraskanir, Psychiatry and Mental health, Schizophrenia, Cohort, Major depressive disorder, Case-Control Studie, Human, medicine.medical_specialty, Bipolar disorder, Article, Cellular and Molecular Neuroscience, 03 medical and health sciences, Geðklofi, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Psychiatry, Þunglyndi, Molecular Biology, 030304 developmental biology, Depressive Disorder, Major, Geðhvarfasýki, business.industry, Psychiatric disorder, medicine.disease, Genarannsóknir, Case-Control Studies, Multiple comparisons problem, business, 030217 neurology & neurosurgery
Abstract

Publisher's version, Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development., The study was supported by the German Federal Ministry of Education and Research (BMBF), through the Integrated Network IntegraMent, under the auspices of the e:Med programme (grants 01ZX1314A to MMN and SC; 01ZX1314G to MR; 01ZX1614J to BMM) through grants 01EE1406C to MR and 01EE1409C to MR and SHW, and through ERA-NET NEURON, “SynSchiz—Linking synaptic dysfunction to disease mechanisms in schizophrenia—a multilevel investigation” (01EW1810 to MR) and BMBF grants 01EE1409C and 01EE1406C to MR and SHW; by the German Research Foundation (DFG grants FOR2107; RI908/11-2 to MR; NO246/10-2 to MMN; MU1315/8-2 to BMM; WI 3439/3-2 to SHW), by the Andalusian regional Health and Innovation Government (grants PI-0060-2017, RC-0006-2015 the Nicolas Monarde Programme for YDO and CTS-546) and by the Swiss National Science Foundation (SNSF grant 156791 to SC). MMN is a member of the DFG-funded cluster of excellence ImmunoSensation. The PGC has received major funding from the US National Institute of Mental Health and the US National Institute of Drug Abuse (U01 MH109528 and U01 MH1095320). We thank the research participants and employees of 23andMe, Inc. for their contribution to the MDD meta-analysis published in [14]. We thank the International Genomics of Alzheimer's Project (IGAP) for providing summary results data for the present analyses. See the Supplementary Data for extended Acknowledgements.

Published
2021

106. Our Readers Write: A Baker's Dozen Books I Would Take with Me If I Were Banished to a Desert Island

Author

Carter, Candy, Chelton, Mary K., Cullinan, Bernice E., Gere, Anne Ruggles, Stewig, John Warren, Farrell, Edmund J., Swift, Jonathan, Squires, Robert, Haley, Beverly, Carlsen, G. Robert, Horst, Bill, Perry, Jesse, Rodrigues, Raymond J., McFarland, Robbie, Cormier, Robert, Forehand, Mildred, Nilsen, Alleen, Donelson, Ken, Nicholson, Skip, Caldwell, Margueritte Johnson, Broz, Nancy, Larkin, Grace, Wilson, Velez, Veidemanis, Gladys V., Whetton, Betty B., Shaw, Dianne, and Christensen, Jane

Published
1982
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107. Anthropometric measures and bladder cancer risk: A prospective study in the EPIC cohort

Author

Roswall, Nina, Freisling, Heinz, Bueno-de-Mesquita, H. B(as), Ros, Martine, Christensen, Jane, Overvad, Kim, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Fagherazzi, Guy, Chang-Claude, Jenny, Kaaks, Rudolf, Steffen, Annika, Boeing, Heiner, Argüelles, Marcial, Agudo, Antonio, Sánchez, María-José, Chirlaque, Maria-Dolores, Gurrea, Aurelio Barricarte, Amiano, Pilar, Wareham, Nick, Khaw, Kay-Tee, Bradbury, Kathryn Erica, Trichopoulou, Antonia, Papatesta, Helen-Maria, Trichopoulos, Dimitrios, Palli, Domenico, Pala, Valeria, Tumino, Rosario, Sacerdote, Carlotta, Mattiello, Amalia, Peeters, Petra H., Ehrnström, Roy, Brennan, Paul, Ferrari, Pietro, Ljungberg, Börje, Norat, Teresa, Gunter, Marc, Riboli, Elio, Weiderpass, Elisabete, and Halkjær, Jytte

Published
2014
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111. Psychotropic medication among children who experience parental death to cancer

Author

Høeg, Beverley Lim, primary, Christensen, Jane, additional, Banko, Linda, additional, Frederiksen, Kirsten, additional, Appel, Charlotte Weiling, additional, Dalton, Susanne Oksbjerg, additional, Dyregrov, Atle, additional, Guldin, Mai-Britt, additional, Jørgensen, Sanne Ellegaard, additional, Lytje, Martin, additional, Bøge, Per, additional, and Bidstrup, Pernille Envold, additional

Published
2021
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112. Outcomes and characteristics of Danish patients undergoing a lung cancer patient pathway without getting a lung cancer diagnosis. A retrospective cohort study

Author

Thomsen Linda Aagaard, Rasmussen Torben Riis, Christensen Jane, Therkildsen Ditte Skadhede, Andersen Ole, and Christensen Niels Lyhne

Subjects
Pulmonary and Respiratory Medicine, Thorax, medicine.medical_specialty, Denmark, Population, pathways, Danish, Diseases of the respiratory system, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, 030212 general & internal medicine, Lung cancer, education, education.field_of_study, urgent referral, RC705-779, invasive examinations, business.industry, Cancer, Retrospective cohort study, medicine.disease, language.human_language, 030228 respiratory system, language, Population study, business, Research Article, Cohort study
Abstract

Introduction: The organ-specific Danish cancer patient pathways (CPPs) including standard time frames were introduced in 2008-2009 securing fast tracks for cancer diagnosis and treatment. Previous studies of the CPPs have focussed on patients getting the suspected cancer diagnosis, whereas little is known about patients not getting the cancer diagnosis for which they were examined. We aimed to describe the characteristics of patients who completed a lung cancer CPP (LCPP) without getting a LC diagnosis. Furthermore, to assess the proportion of patients who had invasive procedures performed during the LCPP and radiographic examinations of the chest conducted 30 days prior to the LCPP and during the LCPP. Moreover, we aimed to describe the proportion of patients being diagnosed with any other cancer-type than LC or with non-malignant pulmonary diseases (NMPDs) during the LCPP. Methods: The study was a retrospective population-based cohort study based on Danish national registers. Patients completing a LCPP between 1 January 2013 and 31 December 2016 without being diagnosed with LC and who were registered as initiating and completing the LCPP, a total of 35,809, were included in the study. Results: Invasive procedures were performed in 12,986 patients (37.4%) and almost all patients had CT-scans of thorax and lungs conducted 30 days prior to or during the LCPP. During the LCPP other cancer-types than LC were diagnosed in 1,537 patients (4.3% of the study population), including other primary thoracic malignancies in 312 patients, while 6,826 patients (19.1%) were diagnosed with NMPDs, most often infections or chronic respiratory diseases of lower airways. Conclusion: Besides diagnosing LC the LCPP may contribute significantly in diagnosing other primary and secondary cancers as well as non-malignant diseases.

Published
2021

113. Clinical effects of assessing electronic patient-reported outcomes monitoring symptomatic toxicities during breast cancer therapy:a nationwide and population-based study

Author

Pappot, Helle, Baeksted, Christina W., Nissen, Aase, Knoop, Ann, Mitchell, Sandra A., Christensen, Jane, Hjollund, Niels Henrik, Johansen, Christoffer, Pappot, Helle, Baeksted, Christina W., Nissen, Aase, Knoop, Ann, Mitchell, Sandra A., Christensen, Jane, Hjollund, Niels Henrik, and Johansen, Christoffer

Abstract

The involvement of cancer patients in symptom reporting talks into our cultural narrative of empowerment and participation in decisions in health of both patients and professionals. Electronic patient-reported outcome (ePRO) is a tool applied for use in such interaction. Based on limited evidence and few empirical studies, health systems are rapidly implementing this instrument in managing patients in active treatment and in follow-up. In a cluster randomized trial of all Danish oncology departments treating breast cancer with adjuvant chemotherapy, we applied ePRO in 347 patients consecutively recruited. Our primary outcome, which was at least one treatment adjustment, was not significantly influenced using ePRO, 34% in the ePRO arm and 41% in the usual care arm received at least one treatment adjustment, p = 0.095. Number of hospitalizations and events of febrile neutropenia were not influenced by the intervention. We believe that one of the main reasons for this finding could be the application of PRO in a well-regulated treatment setting within a public health care system where the most impacting symptomatic toxicities are already taken care off. Trial registration: Clinicaltrials.gov identifier: NCT02996201, registered 19 Dec 2016, retrospectively registered.

Published
2021

114. Breast cancer rate after oophorectomy:A Prospective Danish Cohort Study

Author

Koch, Trine, Jørgensen, Jeanette Therming, Christensen, Jane, Dehlendorff, Christian, Priskorn, Lærke, Simonsen, Mette K., Duun-Henriksen, Anne Katrine, Andersen, Zorana J., Juul, Anders, Bräuner, Elvira V., Hickey, Martha, Koch, Trine, Jørgensen, Jeanette Therming, Christensen, Jane, Dehlendorff, Christian, Priskorn, Lærke, Simonsen, Mette K., Duun-Henriksen, Anne Katrine, Andersen, Zorana J., Juul, Anders, Bräuner, Elvira V., and Hickey, Martha

Abstract

The association between oophorectomy and risk of breast cancer in the general population is uncertain. The aim of our study was to determine the breast cancer rate in women from the general population after oophorectomy (performed before/after menopause), and whether this varies by use of hormone replacement therapy (HRT), hysterectomy, body mass index (BMI) and shift work. The study included 24 409 female nurses (aged ≥45 years) participating in the Danish Nurse Cohort. Nurses were followed from cohort entry until date of breast cancer, death, emigration or end of follow-up at 31 December 2018, whichever came first. Poisson regression with log-transformed person-years as the offset examined the association between oophorectomy and breast cancer (all ages and stratified by menopausal status at time of oophorectomy). The potential modifying effect of HRT use, hysterectomy, BMI and shift work on the associations was estimated. During 502 463 person-years of follow-up, 1975 (8.1%) nurses were diagnosed with breast cancer. Bilateral oophorectomy was associated with a reduced breast cancer rate compared to nurses with preserved ovaries, adjusted rate ratio (95% confidence interval): 0.79 (0.64; 0.99). Similar associations (magnitude and direction) were detected for unilateral oophorectomy and when stratifying according to menopausal status at time of oophorectomy, but without statistical significance. Unilateral and bilateral oophorectomy is associated with a reduced breast cancer rate in women from the general population. This association is not modified by use of HRT, hysterectomy, BMI or shift work.

Published
2021

115. Prediction of the postoperative 90-day mortality after acute colorectal cancer surgery:development and temporal validation of the ACORCA model

Author

Degett, Thea Helene, Christensen, Jane, Dalton, Susanne Oksbjerg, Bossen, Kristine, Frederiksen, Kirsten, Iversen, Lene Hjerrild, Gögenur, Ismail, Degett, Thea Helene, Christensen, Jane, Dalton, Susanne Oksbjerg, Bossen, Kristine, Frederiksen, Kirsten, Iversen, Lene Hjerrild, and Gögenur, Ismail

Abstract

Purpose: The aim of this study was to develop and validate a model to predict 90-day mortality after acute colorectal cancer surgery. Methods: The model was developed in all patients undergoing acute colorectal cancer surgery in 2014–2016 and validated in a patient group operated in 2017 in Denmark. The outcome was 90-day mortality. Tested predictor variables were age, sex, performance status, BMI, smoking, alcohol, education level, cohabitation status, tumour localization and primary surgical procedure. Variables were selected according to the smallest Akaike information criterion. The model was shrunken by bootstrapping. Discrimination was evaluated with a receiver operated characteristic curve, calibration with a calibration slope and the accuracy with a Brier score. Results: A total of 1450 patients were included for development of the model and 451 patients for validation. The 90-day mortality rate was 19% and 20%, respectively. Age, performance status, alcohol, smoking and primary surgical procedure were the final variables included in the model. Discrimination (AUC = 0.79), calibration (slope = 1.04, intercept = 0.04) and accuracy (brier score = 0.13) were good in the developed model. In the temporal validation, discrimination (AUC = 0.80) and accuracy (brier score = 0.13) were good, and calibration was acceptable (slope = 1.19, intercept = 0.52). Conclusion: We developed prediction model for 90-day mortality after acute colorectal cancer surgery that may be a promising tool for surgeons to identify patients at risk of postoperative mortality.

Published
2021

116. Identification of genetic loci associated with nocturnal enuresis:a genome-wide association study

Author

Jørgensen, Cecilie S., Horsdal, Henriette T., Rajagopal, Veera M., Grove, Jakob, Als, Thomas D., Kamperis, Konstantinos, Nyegaard, Mette, Walters, G. Bragi, Eðvarðsson, Viðar Örn, Stefánsson, Hreinn, Nordentoft, Merete, Hougaard, David Michael, Werge, Thomas, Mors, Ole, Mortensen, Preben Bo, Agerbo, Esben, Rittig, Søren, Stefánsson, Kári, Børglum, Anders D., Demontis, Ditte, Christensen, Jane H., Jørgensen, Cecilie S., Horsdal, Henriette T., Rajagopal, Veera M., Grove, Jakob, Als, Thomas D., Kamperis, Konstantinos, Nyegaard, Mette, Walters, G. Bragi, Eðvarðsson, Viðar Örn, Stefánsson, Hreinn, Nordentoft, Merete, Hougaard, David Michael, Werge, Thomas, Mors, Ole, Mortensen, Preben Bo, Agerbo, Esben, Rittig, Søren, Stefánsson, Kári, Børglum, Anders D., Demontis, Ditte, and Christensen, Jane H.

Abstract

Background: Nocturnal enuresis (bedwetting) is a common disorder affecting 10–16% of 7-year-old children globally. Nocturnal enuresis is highly heritable, but its genetic determinants remain unknown. We aimed to identify genetic variants associated with nocturnal enuresis and explore its genetic architecture and underlying biology. Methods: We did a genome-wide association study (GWAS) of nocturnal enuresis. Nocturnal enuresis cases were identified in iPSYCH2012, a large Danish population-based case cohort established to investigate mental disorders, on the basis of 10th revision of the International Statistical Classification of Diseases (ICD-10) diagnoses and redeemed desmopressin prescriptions in Danish registers. The GWAS was done in a genetically homogeneous sample of unrelated individuals using logistic regression with relevant covariates. All genome-wide significant variants were analysed for their association with nocturnal enuresis in an independent Icelandic sample from deCODE genetics. Standardised polygenic risk scores for attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder were constructed from summary statistics of large GWASs and analysed for association with nocturnal enuresis. Findings: The GWAS included 3882 nocturnal enuresis cases and 31 073 controls. We found two loci at chromosome 6 and chromosome 13 significantly associated with nocturnal enuresis. Six genetic variants at the two loci (five variants at chromosome 6q16.2 and one variant at chromosome 13q22.3) surpassed the threshold for genome-wide significance (p<5 × 10−8). There were two lead variants: rs9376454 (chromosome 6q16.2), with an odds ratio (OR) of 1·199 (95% CI 1·135–1·267; p=9·91 × 10−11), and rs60721117 (chromosome 13q22.3), with an OR of 1·149 (1·095–1·205; p=1·21 × 10−8). All associated variants in the chromosome 6 locus were replicated (p<8 × 10−3) in the independent Icelandic cohort of 5475 nocturn

Published
2021

117. Novel variant of AVPR2 giving rise to X-linked congenital nephrogenic diabetes insipidus in a 7-month-old Danish boy

Author

Sollid, Johanne Emy, Joshi, Shivani, Pulczynska Wason, Malgorzata, Rittig, Søren, Hvarregaard Christensen, Jane, and Kamperis, Konstantinos

Subjects
x-linkedcongenital nephrotic diabetes insipidus, antidiuretic hormone receptor 2, Genetic testing, Antidiuretic hormone receptor 2, AVPR2, Case Report, X-linked congenital nephrotic diabetes insipidus, lcsh:Diseases of the genitourinary system. Urology, lcsh:RC870-923, avpr2, genetic testing
Abstract

Patients affected with congenital nephrogenic diabetes insipidus (CNDI) have reduced ability to concentrate urine. Early diagnosis of CNDI is important to avoid recurrent episodes of severe dehydration. We present a Danish male suffering from typical symptoms and diagnosed with CNDI at the age of 7 months. Gene sequencing of this proband and his mother revealed a novel variant in the gene encoding the antidiuretic hormone receptor (AVPR2). The variant is a deletion of nucleotide c.151 in exon 2 of AVPR2 (GenBank NM_000054.4:c.151del). This 1bp deletion is predicted to cause a frameshift that results in tryptophan replacing valine at position 51 in AVPR2 and a premature stop codon three codons downstream (p.Val51Trpfs*3) likely resulting in faulty expression of the receptor. Identification of disease-causing variants such as the one described here contributes to precise diagnosis, especially in carriers and newborns, thus preventing the long-term physical and intellectual disability observed in some CNDI-patients.

Published
2020

122. Diverse vasopressin V2 receptor functionality underlying partial congenital nephrogenic diabetes insipidus

Author

Faerch, Mia, Christensen, Jane H., Rittig, Soren, Johansson, Jan-Ove, Gregersen, Niels, de Zegher, Francis, and Corydon, Thomas J.

Subjects
Diabetes insipidus -- Genetic aspects, Vasopressin -- Physiological aspects, Vasopressin -- Genetic aspects, Genetic variation -- Physiological aspects, Biological sciences
Abstract

Faerch M, Christensen JH, Rittig S, Johansson J-O, Gregersen N, de Zegher F, Corydon TJ. Diverse vasopressin V2 receptor functionality underlying partial congenital nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 297: F1518-F1525, 2009. First published October 7, 2009; doi: 10.1152/ajprenal.00331.2009.--X-linked congenital nephrogenic diabetes insipidus (CNDI) is characterized by a defective renal response to the antidiuretic hormone (AVP) due to variations in the arginine vasopressin receptor 2 (AVPR2) gene. In a unique group of patients, the renal insensitivity to the effects of AVP is incomplete resulting in a partial phenotype. To investigate the molecular defects, two previously published variations in the AVPR2 gene, known to cause a partial CNDI phenotype, were expressed in transiently transfected human embryonic kidney cells. One variation (p.Argl04Cys) is located in the first extracellular loop and the other variation (p.Ser329Arg) is located in the intracellular COOH terminal of the receptor protein. Western blotting showed almost equal amounts of WT-V2R and Argl04Cys-V2R protein at steady state, whereas the level of Ser329Arg-V2R protein was lower. Confocal microscopy established that WT-V2R and Arg 104Cys-V2R are localized on the cellular surface while the Ser329Arg-V2R primarily accumulates within the endoplasmic reticulum resulting in reduced surface expression. Ligand binding analysis demonstrated that the [B.sub.max] for cells expressing Argl04Cys-V2R and Ser329ArgV2R were 14.8- and 2.5-fold lower than [B.sub.max] for WT-V2R, respectively. AVP affinity (1/[K.sub.d]) for WT-V2R and the Ser329Arg-V2R was similar while 1/[K.sub.d] for Argl04Cys-V2R was increased, cAMP assay revealed that cells expressing p.Argl04Cys-V2R or p.Ser329ArgV2R produced 1.7- and 6.8-fold lower amounts of cAMP compared with WT-V2R, respectively. In conclusion, ligand binding and signal transduction capability are dependent on localization of the amino acid variation. Striking divergences at the level of receptor functionality may thus underlie similar clinical phenotypes in CNDI. partial phenotype; arginine vasopressin receptor type 2; heterologous expression doi: 10.1152/ajprenal.00331.2009

Published
2009

123. Surgical treatment and survival from colorectal cancer in Denmark, England, Norway, and Sweden : a population-based study

Author

Majano, Sara Benitez, Di Girolamo, Chiara, Rachet, Bernard, Maringe, Camille, Guren, Marianne Gronlie, Glimelius, Bengt, Iversen, Lene Hjerrild, Schnell, Edrun Andrea, Lundqvist, Kristina, Christensen, Jane, Morris, Melanie, Coleman, Michel P., Walters, Sarah, Benitez Majano, Sara, Di Girolamo, Chiara, Rachet, Bernard, Maringe, Camille, Guren, Marianne Grønlie, Glimelius, Bengt, Iversen, Lene Hjerrild, Schnell, Edrun Andrea, Lundqvist, Kristina, Christensen, Jane, Morris, Melanie, Coleman, Michel P, and Walters, Sarah

Subjects
Adult, Male, Adolescent, diagnosis, Denmark, surgical treatment, Adenocarcinoma, Scandinavian and Nordic Countries, survival, Article, rectal-cancer, surgery, Young Adult, Humans, cancer, Registries, Colectomy, radiotherapy, Aged, Sweden, Aged, 80 and over, Cancer och onkologi, Norway, Age Factors, registries, Middle Aged, Survival Analysis, older patients, adjuvant chemotherapy, England, Cancer and Oncology, Multivariate Analysis, Female, complete mesocolic excision, cancer, survival, surgical treatment, Colorectal Neoplasms, management, metaanalysis
Abstract

Background Survival from colorectal cancer has been shown to be lower in Denmark and England than in comparable high-income countries. We used data from national colorectal cancer registries to assess whether differences in the proportion of patients receiving resectional surgery could contribute to international differences in colorectal cancer survival. Methods In this population-based study, we collected data from all patients aged 18–99 years diagnosed with primary, invasive, colorectal adenocarcinoma from Jan 1, 2010, to Dec 31, 2012, in Denmark, England, Norway, and Sweden, from national colorectal cancer registries. We estimated age-standardised net survival using multivariable modelling, and we compared the proportion of patients receiving resectional surgery by stage and age. We used logistic regression to predict the resectional surgery status patients would have had if they had been treated as in the best performing country, given their individual characteristics. Findings We extracted registry data for 139457 adult patients with invasive colorectal adenocarcinoma: 12958 patients in Denmark, 97466 in England, 11450 in Norway, and 17583 in Sweden. 3-year colon cancer survival was lower in England (63·9%, 95% CI 63·5–64·3) and Denmark (65·7%, 64·7–66·8) than in Norway (69·5%, 68·4–70·5) and Sweden (72·1%,71·2–73·0). Rectal cancer survival was lower in England (69·7%, 69·1–70·3) than in the other three countries (Denmark 72·5%, 71·1–74·0; Sweden 74·1%, 72·7–75·4; and Norway 75·0%, 73·1–76·8). We found no significant differences in survival for patients with stage I disease in any of the four countries. 3-year survival after stage II or III rectal cancer and stage IV colon cancer was consistently lower in England (stage II rectal cancer 86·4%, 95% CI 85·0–87·6; stage III rectal cancer 75·5%, 74·2–76·7; and stage IV colon cancer 20·5%, 19·9–21·1) than in Norway (94·1%, 91·5–96·0; 83·4%, 80·1–86·1; and 33·0%, 31·0–35·1) and Sweden (92·9%, 90·8–94·6; 80·6%, 78·2–82·7; and 23·7%, 22·0–25·3). 3-year survival after stage II rectal cancer and stage IV colon cancer was also lower in England than in Denmark (stage II rectal cancer 91·2%, 88·8–93·1; and stage IV colon cancer 23·5%, 21·9–25·1). The total proportion of patients treated with resectional surgery ranged from 47803 (68·4%) of 69867 patients in England to 9582 (81·3%) of 11786 in Sweden for colon cancer, and from 16544 (59·9%) of 27599 in England to 4106 (70·8%) of 5797 in Sweden for rectal cancer. This range was widest for patients older than 75 years (colon cancer 19078 [59·7%] of 31946 patients in England to 4429 [80·9%] of 5474 in Sweden; rectal cancer 4663 [45·7%] of 10195 in England to 1342 [61·9%] of 2169 in Sweden), and the proportion of patients treated with resectional surgery was consistently lowest in England. The age gradient of the decline in the proportion of patients treated with resectional surgery was steeper in England than in the other three countries in all stage categories. In the hypothetical scenario where all patients were treated as in Sweden, given their age, sex, and disease stage, the largest increase in resectional surgery would be for patients with stage III rectal cancer in England (increasing from 70·3% to 88·2%). Interpretation Survival from colon cancer and rectal cancer in England and colon cancer in Denmark was lower than in Norway and Sweden. Survival paralleled the relative provision of resectional surgery in these countries. Differences in patient selection for surgery, especially in patients older than 75 years or individuals with advanced disease, might partly explain these differences in international colorectal cancer survival.

Published
2019

124. Breast cancer rate after oophorectomy: A Prospective Danish Cohort Study

Author

Koch, Trine, primary, Jørgensen, Jeanette Therming, additional, Christensen, Jane, additional, Dehlendorff, Christian, additional, Priskorn, Lærke, additional, Simonsen, Mette K., additional, Duun‐Henriksen, Anne Katrine, additional, Andersen, Zorana J., additional, Juul, Anders, additional, Bräuner, Elvira V., additional, and Hickey, Martha, additional

Published
2021
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125. Identification of genetic loci associated with nocturnal enuresis: a genome-wide association study

Author

Jørgensen, Cecilie S, primary, Horsdal, Henriette T, additional, Rajagopal, Veera M, additional, Grove, Jakob, additional, Als, Thomas D, additional, Kamperis, Konstantinos, additional, Nyegaard, Mette, additional, Walters, G Bragi, additional, Eðvarðsson, Viðar Örn, additional, Stefánsson, Hreinn, additional, Nordentoft, Merete, additional, Hougaard, David Michael, additional, Werge, Thomas, additional, Mors, Ole, additional, Mortensen, Preben Bo, additional, Agerbo, Esben, additional, Rittig, Søren, additional, Stefánsson, Kári, additional, Børglum, Anders D, additional, Demontis, Ditte, additional, and Christensen, Jane H, additional

Published
2021
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127. A Partial Phenotype of adFNDI Related to the Signal Peptide c.55G>A Variant of the AVP Gene

Author

Tocci, Vera, primary, Mirabelli, Maria, additional, Giuliano, Stefania, additional, Chiefari, Eusebio, additional, Hagelskjær Knudsen, Jane, additional, Kvistgaard, Helene, additional, La Torre, Domenico, additional, Aversa, Antonio, additional, Foti, Daniela Patrizia, additional, Hvarregaard Christensen, Jane, additional, and Brunetti, Antonio, additional

Published
2021
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129. Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression

Author

Glanville, Kylie P, Coleman, Jonathan R I, Binder, Elisabeth B, Hall, Lynsey S, Hansen, Christine Søholm, Hansen, Thomas F, Herms, Stefan, Hickie, Ian B, Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M, Blackwood, Douglas H R, Howard, David M, Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A, Jorgenson, Eric, Knowles, James A, Kohane, Isaac S, Kraft, Julia, Kretzschmar, Warren W, Boomsma, Dorret I, Kutalik, Zoltán, Li, Yihan, Lind, Penelope A, MacIntyre, Donald J, MacKinnon, Dean F, Maier, Robert M, Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, Buttenschøn, Henriette N, McGuffin, Peter, Medland, Sarah E, Mehta, Divya, Middeldorp, Christel M, Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M, Montgomery, Grant W, Mostafavi, Sara, Colodro-Conde, Lucía, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G, Nyholt, Dale R, O'Reilly, Paul F, Oskarsson, Hogni, Owen, Michael J, Painter, Jodie N, Pedersen, Carsten Bøcker, Dannlowski, Udo, Pedersen, Marianne Giørtz, Peterson, Roseann E, Pettersson, Erik, Peyrot, Wouter J, Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A, Qvist, Per, Rice, John P, Riley, Brien P, Direk, Nese, Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C, Shen, Ling, Shi, Jianxin, Shyn, Stanley I, Sigurdsson, Engilbert, Sinnamon, Grant C B, Smit, Johannes H, Dunn, Erin C, Smith, Daniel J, Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E, Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A, Forstner, Andreas J, Thorgeirsson, Thorgeir E, Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, Andrés G, Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M, Viktorin, Alexander, Visscher, Peter M, de Geus, Eco J C, Wang, Yunpeng, Webb, Bradley T, Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H, Wu, Yang, Xi, Hualin S, Yang, Jian, Zhang, Futao, Hanscombe, Ken B, Grabe, Hans J, Arolt, Volker, Baune, Bernhard T, Berger, Klaus, Cichon, Sven, de Geus, E. J. C., DePaulo, J Raymond, Domenici, Enrico, Domschke, Katharina, Hamilton, Steven P, Esko, Tõnu, Hayward, Caroline, Heath, Andrew C, Kendler, Kenneth S, Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S, Lucae, Susanne, Madden, Pamela Af, Magnusson, Patrik K, Martin, Nicholas G, McIntosh, Andrew M, Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, Nöthen, Markus M, O'Donovan, Michael C, Paciga, Sara A, Pedersen, Nancy L, Penninx, Brenda W J H, Perlis, Roy H, Porteous, David J, Potash, James B, Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G, Smoller, Jordan W, Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M, Werge, Thomas, Lewis, Cathryn M, Levinson, Douglas F, Breen, Gerome, Børglum, Anders D, Sullivan, Patrick F, Euesden, Jack, Choi, Shing Wan, Ripke, Stephan, Purves, Kirstin L, Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics, Wray, Naomi R, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M, Abdellaoui, Abdel, Adams, Mark J, Agerbo, Esben, Air, Tracy M, Andlauer, Till F M, Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T F, Bigdeli, Tim B, Bryois, Julien, Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E, Davies, Gail, Deary, Ian J, Degenhardt, Franziska, Derks, Eske M, Dolan, Conor V, Eley, Thalia C, Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K, Foo, Jerome C, Frank, Josef, Gaspar, Héléna A, Gill, Michael, Goes, Fernando S, Gordon, Scott D, Grove, Jakob, Adult Psychiatry, APH - Mental Health, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Wray, N.R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., Adams, M.J., Agerbo, E., Air, T.M., Andlauer, TFM, Bacanu, S.A., Bækvad-Hansen, M., Beekman, ATF, Bigdeli, T.B., Binder, E.B., Bryois, J., Buttenschøn, H.N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Christensen, J.H., Clarke, T.K., Coleman, JRI, Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G.E., Davies, G., Deary, I.J., Degenhardt, F., Derks, E.M., Direk, N., Dolan, C.V., Dunn, E.C., Eley, T.C., Escott-Price, V., Hassan Kiadeh, F.F., Finucane, H.K., Foo, J.C., Forstner, A.J., Frank, J., Gaspar, H.A., Gill, M., Goes, F.S., Gordon, S.D., Grove, J., Hall, L.S., Hansen, C.S., Hansen, T.F., Herms, S., Hickie, I.B., Hoffmann, P., Homuth, G., Horn, C., Hottenga, J.J., Hougaard, D.M., Howard, D.M., Ising, M., Jansen, R., Jones, I., Jones, L.A., Jorgenson, E., Knowles, J.A., Kohane, I.S., Kraft, J., Kretzschmar, W.W., Kutalik, Z., Li, Y., Lind, P.A., MacIntyre, D.J., MacKinnon, D.F., Maier, R.M., Maier, W., Marchini, J., Mbarek, H., McGrath, P., McGuffin, P., Medland, S.E., Mehta, D., Middeldorp, C.M., Mihailov, E., Milaneschi, Y., Milani, L., Mondimore, F.M., Montgomery, G.W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R., O'Reilly, P.F., Oskarsson, H., Owen, M.J., Painter, J.N., Pedersen, C.B., Pedersen, M.G., Peterson, R.E., Pettersson, E., Peyrot, W.J., Pistis, G., Posthuma, D., Quiroz, J.A., Qvist, P., Rice, J.P., Riley, B.P., Rivera, M., Mirza, S.S., Schoevers, R., Schulte, E.C., Shen, L., Shi, J., Shyn, S.I., Sigurdsson, E., Sinnamon, GCB, Smit, J.H., Smith, D.J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K.E., Teismann, H., Teumer, A., Thompson, W., Thomson, P.A., Thorgeirsson, T.E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A.G., Umbricht, D., Van der Auwera, S., van Hemert, A.M., Viktorin, A., Visscher, P.M., Wang, Y., Webb, B.T., Weinsheimer, S.M., Wellmann, J., Willemsen, G., Witt, S.H., Wu, Y., Xi, H.S., Yang, J., Zhang, F., Arolt, V., Baune, B.T., Berger, K., Boomsma, D.I., Cichon, S., Dannlowski, U., de Geus, E., DePaulo, J.R., Domenici, E., Domschke, K., Esko, T., Grabe, H.J., Hamilton, S.P., Hayward, C., Heath, A.C., Kendler, K.S., Kloiber, S., Lewis, G., Li, Q.S., Lucae, S., Madden, P.A., Magnusson, P.K., Martin, N.G., McIntosh, A.M., Metspalu, A., Mors, O., Mortensen, P.B., Müller-Myhsok, B., Nordentoft, M., Nöthen, M.M., O'Donovan, M.C., Paciga, S.A., Pedersen, N.L., Penninx, BWJH, Perlis, R.H., Porteous, D.J., Potash, J.B., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T.G., Smoller, J.W., Stefansson, K., Tiemeier, H., Uher, R., Völzke, H., Weissman, M.M., Werge, T., Lewis, C.M., Levinson, D.F., Breen, G., Børglum, A.D., Sullivan, P.F., Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Biological Psychology, APH - Methodology, Functional Genomics, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Complex Trait Genetics, Epidemiology, Child and Adolescent Psychiatry / Psychology, Psychiatry, Internal Medicine, Human genetics, Amsterdam Reproduction & Development (AR&D), APH - Digital Health, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), and Perceptual and Cognitive Neuroscience (PCN)

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Major histocompatibility complex, LOCI, Complement, Autoimmune disorder, Genome-wide association study, Human leukocyte antigen, Genetic association, Major depressive disorder, Article, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, HLA Antigens, Genetic predisposition, IMPUTATION, Humans, ANXIETY, Genetic Predisposition to Disease, ddc:610, GENOME-WIDE ASSOCIATION, AUTOIMMUNE-DISEASE, Biological Psychiatry, Alleles, Complement component 4, Depressive Disorder, Major, Major histoconnpatibility complex, COMPLEX, biology, Depression, Haplotype, Odds ratio, ddc, 3. Good health, 030104 developmental biology, Haplotypes, Immunology, biology.protein, RISK-FACTORS, INFERENCE, HEALTH, 030217 neurology & neurosurgery
Abstract

Background\ud \ud The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression.\ud \ud \ud Methods\ud \ud We fine-mapped the classical MHC (chr6: 29.6–33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10−6) and a candidate threshold (1.6 × 10−4).\ud \ud \ud Results\ud \ud No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97–0.99).\ud \ud \ud Conclusions\ud \ud We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

Published
2020

130. Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

Author

Coleman, Jonathan RI, Peyrot, Wouter J, Purves, Kirstin L, Davis, Katrina AS, Rayner, Christopher, Choi, Shing Wan, Hubel, Christopher, Gaspar, Helena A, Kan, Carol, Van der Auwera, Sandra, Adams, Mark James, Lyall, Donald M, Choi, Karmel W, Dunn, Erin C, Vassos, Evangelos, Danese, Andrea, Maughan, Barbara, Grabe, Hans J, Lewis, Cathryn M, O'Reilly, Paul F, McIntosh, Andrew M, Smith, Daniel J, Wray, Naomi R, Hotopf, Matthew, Eley, Thalia C, Breen, Gerome, Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M, Abdellaoui, Abdel, Adams, Mark J, Agerbo, Esben, Air, Tracy M, Andlauer, Till FM, Bacanu, Silviu-Alin, Baekvad-Hansen, Marie, Beekman, Aartjan TF, Bigdeli, Tim B, Binder, Elisabeth B, Bryois, Julien, Buttenschon, Henriette N, Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Colodro-Conde, Lucia, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E, Davies, Gail, Deary, Ian J, Degenhardt, Franziska, Derks, Eske M, Direk, Nese, Dolan, Conor V, Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K, Foo, Jerome C, Forstner, Andreas J, Frank, Josef, Gill, Michael, Goes, Fernando S, Gordon, Scott D, Grove, Jakob, Hall, Lynsey S, Hansen, Christine Soholm, Hansen, Thomas F, Herms, Stefan, Hickie, Ian B, Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M, Howard, David M, Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A, Jorgenson, Eric, Knowles, James A, Kohane, Isaac S, Kraft, Julia, Kretzschmar, Warren W, Kutalik, Zoltan, Li, Yihan, Lind, Penelope A, MacIntyre, Donald J, MacKinnon, Dean F, Maier, Robert M, Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E, Mehta, Divya, Middeldorp, Christel M, Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M, Montgomery, Grant W, Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G, Nyholt, Dale R, Oskarsson, Hogni, Owen, Michael J, Painter, Jodie N, Pedersen, Carsten Bocker, Pedersen, Marianne Giortz, Peterson, Roseann E, Pettersson, Erik, Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A, Qvist, Per, Rice, John P, Riley, Brien P, Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C, Shen, Ling, Shi, Jianxin, Shyn, Stanley I, Sigurdsson, Engilbert, Sinnamon, Grant CB, Smit, Johannes H, Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E, Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A, Thorgeirsson, Thorgeir E, Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, Andres G, Umbricht, Daniel, van Hemert, Albert M, Viktorin, Alexander, Visscher, Peter M, Wang, Yunpeng, Webb, Bradley T, Weinsheimer, Shantel Marie, Wellmann, Jurgen, Willemsen, Gonneke, Witt, Stephanie H, Wu, Yang, Xi, Hualin S, Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T, Berger, Klaus, Boomsma, Dorret I, Cichon, Sven, Dannlowski, Udo, de Geus, EJC, DePaulo, J Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tonu, Hamilton, Steven P, Hayward, Caroline, Heath, Andrew C, Kendler, Kenneth S, Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S, Lucae, Susanne, Madden, Pamela AF, Magnusson, Patrik K, Martin, Nicholas G, Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Mueller-Myhsok, Bertram, Nordentoft, Merete, Noethen, Markus M, O'Donovan, Michael C, Paciga, Sara A, Pedersen, Nancy L, Penninx, Brenda WJH, Perlis, Roy H, Porteous, David J, Potash, James B, Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G, Smoller, Jordan W, Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Volzke, Henry, Weissman, Myrna M, Werge, Thomas, Levinson, Douglas F, Borglum, Anders D, Sullivan, Patrick F, Consortium, Psychiat Genomics, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Amsterdam Reproduction & Development (AR&D), Human genetics, APH - Methodology, APH - Digital Health, Adult Psychiatry, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Sociology and Social Gerontology, Complex Trait Genetics, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), on the behalf of Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Wray, N.R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., Adams, M.J., Agerbo, E., Air, T.M., Andlauer, TFM, Bacanu, S.A., Bækvad-Hansen, M., Beekman, ATF, Bigdeli, T.B., Binder, E.B., Bryois, J., Buttenschøn, H.N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Christensen, J.H., Clarke, T.K., Coleman, JRI, Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G.E., Davies, G., Deary, I.J., Degenhardt, F., Derks, E.M., Direk, N., Dolan, C.V., Dunn, E.C., Eley, T.C., Escott-Price, V., Kiadeh, FFH, Finucane, H.K., Foo, J.C., Forstner, A.J., Frank, J., Gaspar, H.A., Gill, M., Goes, F.S., Gordon, S.D., Grove, J., Hall, L.S., Hansen, C.S., Hansen, T.F., Herms, S., Hickie, I.B., Hoffmann, P., Homuth, G., Horn, C., Hottenga, J.J., Hougaard, D.M., Howard, D.M., Ising, M., Jansen, R., Jones, I., Jones, L.A., Jorgenson, E., Knowles, J.A., Kohane, I.S., Kraft, J., Kretzschmar, W.W., Kutalik, Z., Li, Y., Lind, P.A., MacIntyre, D.J., MacKinnon, D.F., Maier, R.M., Maier, W., Marchini, J., Mbarek, H., McGrath, P., McGuffin, P., Medland, S.E., Mehta, D., Middeldorp, C.M., Mihailov, E., Milaneschi, Y., Milani, L., Mondimore, F.M., Montgomery, G.W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R., O'Reilly, P.F., Oskarsson, H., Owen, M.J., Painter, J.N., Pedersen, C.B., Pedersen, M.G., Peterson, R.E., Pettersson, E., Peyrot, W.J., Pistis, G., Posthuma, D., Quiroz, J.A., Qvist, P., Rice, J.P., Riley, B.P., Rivera, M., Mirza, S.S., Schoevers, R., Schulte, E.C., Shen, L., Shi, J., Shyn, S.I., Sigurdsson, E., Sinnamon, GCB, Smit, J.H., Smith, D.J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K.E., Teismann, H., Teumer, A., Thompson, W., Thomson, P.A., Thorgeirsson, T.E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A.G., Umbricht, D., Van der Auwera, S., van Hemert, A.M., Viktorin, A., Visscher, P.M., Wang, Y., Webb, B.T., Weinsheimer, S.M., Wellmann, J., Willemsen, G., Witt, S.H., Wu, Y., Xi, H.S., Yang, J., Zhang, F., Arolt, V., Baune, B.T., Berger, K., Boomsma, D.I., Cichon, S., Dannlowski, U., de Geus, EJC, DePaulo, J.R., Domenici, E., Domschke, K., Esko, T., Grabe, H.J., Hamilton, S.P., Hayward, C., Heath, A.C., Kendler, K.S., Kloiber, S., Lewis, G., Li, Q.S., Lucae, S., Madden, PAF, Magnusson, P.K., Martin, N.G., McIntosh, A.M., Metspalu, A., Mors, O., Mortensen, P.B., Müller-Myhsok, B., Nordentoft, M., Nöthen, M.M., O'Donovan, M.C., Paciga, S.A., Pedersen, N.L., Penninx, BWJH, Perlis, R.H., Porteous, D.J., Potash, J.B., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T.G., Smoller, J.W., Stefansson, K., Tiemeier, H., Uher, R., Völzke, H., Weissman, M.M., Werge, T., Lewis, C.M., Levinson, D.F., Breen, G., Børglum, A.D., and Sullivan, P.F.

Subjects
Netherlands Twin Register (NTR), 0301 basic medicine, Male, SYMPTOMS, Databases, Factual, Genome-wide association study, 0302 clinical medicine, Medicine, Depression (differential diagnoses), RISK, HERITABILITY, PSYCHIATRIC-DISORDERS, Middle Aged, Psychiatry and Mental health, Major depressive disorder, Female, Waist Circumference, MENTAL-HEALTH, Psychological trauma, Clinical psychology, Adult, Psychological Trauma, Genetic correlation, CHILDHOOD MALTREATMENT, Article, EVENTS, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, ADVERSITY, mental disorders, SNP, Humans, Genetic Predisposition to Disease, Molecular Biology, Genetic association, Aged, Depressive Disorder, Major, business.industry, Heritability, medicine.disease, United Kingdom, ASSOCIATION ANALYSIS, 030104 developmental biology, BIOLOGICAL INSIGHTS, Gene-Environment Interaction, Self Report, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (r g = 0.24, p = 1.8 × 10 -7 versus r g = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10 -4 ). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

Published
2020

131. A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

Author

Shen, Xueyi, Howard, David M, McIntosh, Andrew M, O'Reilly, Paul F, Oskarsson, Hogni, Owen, Michael J, Painter, Jodie N, Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E, Pettersson, Erik, Peyrot, Wouter J, Pistis, Giorgio, Deary, Ian J, Posthuma, Danielle, Quiroz, Jorge A, Qvist, Per, Rice, John P, Riley, Brien P, Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C, Shen, Ling, Wray, Naomi R, Shi, Jianxin, Shyn, Stanley I, Sigurdsson, Engilbert, Sinnamon, Grant C B, Smit, Johannes H, Smith, Daniel J, Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Ripke, Stephan, Tansey, Katherine E, Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A, Thorgeirsson, Thorgeir E, Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, Andrés G, Mattheisen, Manuel, Umbricht, Daniel, Auwera, Sandra Van der, van Hemert, Albert M, Viktorin, Alexander, Visscher, Peter M, Wang, Yunpeng, Webb, Bradley T, Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Trzaskowski, Maciej, Witt, Stephanie H, Wu, Yang, Xi, Hualin S, Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T, Berger, Klaus, Boomsma, Dorret I, Cichon, Sven, Byrne, Enda M, Dannlowski, Udo, de Geus, E. J. C., DePaulo, J Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J, Hamilton, Steven P, Hayward, Caroline, Heath, Andrew C, Abdellaoui, Abdel, Kendler, Kenneth S, Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S, Lucae, Susanne, Madden, Pamela A F, Magnusson, Patrik K, Martin, Nicholas G, Metspalu, Andres, Mors, Ole, Agerbo, Esben, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, Nöthen, Markus M, O'Donovan, Michael C, Paciga, Sara A, Pedersen, Nancy L, Penninx, Brenda W J H, Perlis, Roy H, Porteous, David J, Air, Tracy M, Potash, James B, Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G, Smoller, Jordan W, Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Adams, Mark J, Andlauer, Till F M, Weissman, Myrna M, Werge, Thomas, Lewis, Cathryn M, Levinson, Douglas F, Breen, Gerome, Børglum, Anders D, Sullivan, Patrick F, Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T F, Bigdeli, Tim B, Binder, Elisabeth B, Bryois, Julien, Buttenschøn, Henriette N, Bybjerg-Grauholm, Jonas, Cai, Na, Hill, W David, Castelao, Enrique, Christensen, Jane Hvarregaard, Coleman, Jonathan R I, Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E, Davies, Gail, Degenhardt, Franziska, Derks, Eske M, Clarke, Toni-Kim, Direk, Nese, Dolan, Conor V, Dunn, Erin C, Eley, Thalia C, Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K, Foo, Jerome C, Forstner, Andreas J, Frank, Josef, Gaspar, Héléna A, Gill, Michael, Goes, Fernando S, Gordon, Scott D, Grove, Jakob, Hall, Lynsey S, Hansen, Christine Søholm, Hansen, Thomas F, Herms, Stefan, Hickie, Ian B, Whalley, Heather C, Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M, Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A, Jorgenson, Eric, Knowles, James A, Kohane, Isaac S, Kraft, Julia, Kretzschmar, Warren W, Kutalik, Zoltán, Li, Yihan, Lind, Penelope A, MacIntyre, Donald J, MacKinnon, Dean F, Maier, Robert M, Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E, Mehta, Divya, Middeldorp, Christel M, Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M, Montgomery, Grant W, Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G, Nyholt, Dale R, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatry, Human genetics, APH - Methodology, Epidemiology and Data Science, APH - Digital Health, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Complex Trait Genetics, Adult Psychiatry, Shen, Xueyi [0000-0002-0538-4774], Howard, David M [0000-0002-6005-1972], Adams, Mark J [0000-0002-3599-6018], Whalley, Heather C [0000-0002-4505-8869], McIntosh, Andrew M [0000-0002-0198-4588], Apollo - University of Cambridge Repository, Epidemiology, Erasmus MC other, Urology, Child and Adolescent Psychiatry / Psychology, Internal Medicine, Medical Informatics, Immunology, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, and University of Iceland

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), DISORDER, Male, General Physics and Astronomy, Genome-wide association study, Genome-wide association studies, 0302 clinical medicine, Risk Factors, SCHIZOPHRENIA, Medicine, lcsh:Science, Depression (differential diagnoses), Biological Specimen Banks, Multidisciplinary, Depression, Phenome-wide association, Mendelian Randomization Analysis, Middle Aged, Biobank, 3. Good health, ENVIRONMENT INTERACTION, symbols, Female, ddc:500, Clinical psychology, Science, Prefrontal Cortex, Genomics, Neuroimaging, Phenome, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, symbols.namesake, SDG 3 - Good Health and Well-being, Humans, Genetic Predisposition to Disease, Mendelian Randomisation, Þunglyndi, Aged, business.industry, General Chemistry, MAJOR DEPRESSION, Mental health, Genarannsóknir, 030104 developmental biology, Mendelian inheritance, lcsh:Q, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Publisher's version (útgefin grein), Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, pFDR, The present study is supported by a Wellcome Trust Strategic Award “Stratifying Resilience and Depression Longitudinally” (STRADL) (Reference 104036/Z/14/Z) and MRC Mental Health Data Pathfinder Award (Reference MC_PC_17209). Data acquisition and analyses were conducted using the UK Biobank Resource under approved project #4844. Participation of the UK Biobank subjects is gratefully appreciated. We also thank UK Biobank team for collecting and preparing data for analyses. Funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. The PGC has received major funding from the US National Institute of Mental Health (5 U01MH109528-03). We thank the research participants and employees of 23andMe for supporting this study. X.S. receives support from China Scholarship Council (No. 201506040037). H.C.W. is supported by a JMAS SIM fellowship from the Royal College of Physicians of Edinburgh and by an ESAT College Fellowship from the University of Edinburgh. D.M.H. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Reference 213674/Z/18/Z) and a 2018 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Reference 27404). W.D.H. is supported by a grant from Age UK (Disconnected Mind Project). A.M.M. is supported by the Sackler Trust. I.J.D. is a participant in UK Biobank.

Published
2020

132. Classical Human Leukocyte Antigen Alleles And C4 Haplotypes Are Not Significantly Associated With Depression

Author

Glanville, Kylie P., Coleman, Jonathan R.I., Hanscombe, Ken B., Euesden, Jack, Choi, Shing Wan, Purves, Kirstin L., Breen, Gerome, Air, Tracy M., Andlauer, Till F.M., Baune, Bernhard T., Binder, Elisabeth B., Blackwood, Douglas H.R., Boomsma, Dorret I., Buttenschøn, Henriette N., Colodro-Conde, Lucía, Dannlowski, Udo, Direk, Nese, Dunn, Erin C., Forstner, Andreas J., de Geus, Eco J.C., Grabe, Hans J., Hamilton, Steven P., Jones, Ian, Jones, Lisa A., Knowles, James A., Kutalik, Zoltán, Levinson, Douglas F., Lewis, Glyn, Lind, Penelope A., Lucae, Susanne, Magnusson, Patrik K., McGuffin, Peter, McIntosh, Andrew M., Milaneschi, Yuri, Mors, Ole, Mostafavi, Sara, Müller-Myhsok, Bertram, Pedersen, Nancy L., Penninx, Brenda W.J.H., Potash, James B., Preisig, Martin, Ripke, Stephan, Shi, Jianxin, Shyn, Stanley I., Smoller, Jordan W., Streit, Fabian, Sullivan, Patrick F., Tiemeier, Henning, Uher, Rudolf, Van der Auwera, Sandra, Weissman, Myrna M., O'Reilly, Paul F., Lewis, Cathryn M., Wray, Naomi R., Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T.F., Bigdeli, Tim B., Bryois, Julien, Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Derks, Eske M., Dolan, Conor V., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., and Foo, Jerome C.

Published
2020
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133. Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

Author

Coleman, Jonathan R.I., Peyrot, Wouter J., Purves, Kirstin L., Davis, Katrina A.S., Rayner, Christopher, Choi, Shing Wan, Hübel, Christopher, Gaspar, Helena A., Kan, Carol, Van der Auwera, Sandra, Adams, Mark J., Lyall, Donald M., Choi, Karmel W., Wray, Naomi R., Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Agerbo, Esben, Air, Tracy M., Andlauer, Till F.M., Bacanu, Silviu Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T.F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni Kim, Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gill, Michael, Goes, Fernando S., Gordon, Scott D., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke Jan, Hougaard, David M., Howard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., O’Reilly, Paul F., Oskarsson, Hogni, Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Pettersson, Erik, Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C.B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, Andrés G., Umbricht, Daniel, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E. J.C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A.F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, Nöthen, Markus M., O’Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Penninx, Brenda W.J.H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., Vassos, Evangelos, Danese, Andrea, Maughan, Barbara, Hotopf, Matthew, Coleman, Jonathan R.I., Peyrot, Wouter J., Purves, Kirstin L., Davis, Katrina A.S., Rayner, Christopher, Choi, Shing Wan, Hübel, Christopher, Gaspar, Helena A., Kan, Carol, Van der Auwera, Sandra, Adams, Mark J., Lyall, Donald M., Choi, Karmel W., Wray, Naomi R., Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Agerbo, Esben, Air, Tracy M., Andlauer, Till F.M., Bacanu, Silviu Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T.F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni Kim, Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gill, Michael, Goes, Fernando S., Gordon, Scott D., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke Jan, Hougaard, David M., Howard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., O’Reilly, Paul F., Oskarsson, Hogni, Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Pettersson, Erik, Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C.B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, Andrés G., Umbricht, Daniel, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E. J.C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A.F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, Nöthen, Markus M., O’Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Penninx, Brenda W.J.H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., Vassos, Evangelos, Danese, Andrea, Maughan, Barbara, and Hotopf, Matthew

Abstract

Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094–92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8 × 10−7 versus rg = −0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10−4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

Published
2020

134. Registrations of Patients with Renal Cell Carcinoma in the Nationwide Danish Renal Cancer Database versus the Danish Cancer Registry: Data Quality, Completeness and Survival (DaRenCa Study-3)

Author

Danckert,Bolette, Horsbøl,Trine Allerslev, Andersen,Ole, Dalton,Susanne Oksbjerg, Christensen,Jane, Rasted,Margit, Petersen,Astrid, Nørgaard,Mette, Azawi,Nessn, Lund,Lars, Donskov,Frede, Danckert,Bolette, Horsbøl,Trine Allerslev, Andersen,Ole, Dalton,Susanne Oksbjerg, Christensen,Jane, Rasted,Margit, Petersen,Astrid, Nørgaard,Mette, Azawi,Nessn, Lund,Lars, and Donskov,Frede

Abstract

Bolette Danckert,1 Trine Allerslev Horsbøl,2 Ole Andersen,1 Susanne Oksbjerg Dalton,2,3 Jane Christensen,4 Margit Rasted,5 Astrid Petersen,6 Mette Nørgaard,7 Nessn Azawi,8 Lars Lund,9 Frede Donskov10 1Director´s Office, Danish Cancer Society Research Center, Copenhagen, Denmark; 2Survivorship and Inequality in Cancer, Danish Cancer Society Research Center, Copenhagen, Denmark; 3Department of Clinical Oncology & Palliative Care, Zealand University Hospital, Næstved, Denmark; 4Statistics and Data Analysis, Danish Cancer Society Research Center, Copenhagen, Denmark; 5Danish Health Data Authority, Copenhagen, Denmark; 6Department of Pathology, Aalborg University Hospital, Aalborg, Denmark; 7Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 8Department of Urology, Zealand University Hospital, Roskilde, Denmark; 9Department of Urology and Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 10Department of Oncology, Aarhus University Hospital, Aarhus, DenmarkCorrespondence: Frede DonskovDepartment of Oncology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N 8200, DenmarkTel +45 4046 5234Email frede.donskov@auh.rm.dkBackground: The Danish multidisciplinary renal cancer group (DaRenCa) established the nationwide database DaRenCaData in 2010. The Danish Cancer Registry (DCR) has been considered the golden standard. In contrast to DCR, DaRenCaData required the diagnosis to be histologically or cytologically verified. DaRenCaData and DCR have not previously been compared.Patients and Methods: We included patients with renal cell carcinoma registered in DaRenCaData and/or DCR from August 1st 2010 to December 31st 2015. We computed completeness and positive predictive value (PPV) of a diagnosis in DaRenCaData compared with DCR, 1-year, 3-year and 5-year mortality rate ratios, and relative survival.Results: We identified 4890 patients in the two reg

Published
2020

135. Dietary carbohydrate intake is not associated with the breast cancer incidence rate ratio in postmenopausal Danish women

Author

Nielsen, Trine G., Olsen, Anja, Christensen, Jane, Overvad, Kim, and Tjonneland, Anne

Subjects
Breast cancer -- Diet therapy, High-carbohydrate diet -- Health aspects, Food/cooking/nutrition
Abstract

Although many case-control studies have suggested positive associations between carbohydrate intake and breast cancer incidence rates in both pre- and postmenopausal women, there is limited information available from cohort studies. We examined the effect of the intake of different carbohydrates, the glycemic index, and the glycemic load on breast cancer incidence in postmenopausal women taking into consideration tumor estrogen receptor status. Postmenopausal women (n = 23,870; aged 50-65 y) participated in the 'Diet, Cancer, and Health' study, and provided information about diet and established risk factors for breast cancer. During follow-up, we identified 634 incidents of breast cancer. Associations between carbohydrate intake and breast cancer incidence were analyzed using Cox's regression models. There was no association for intake of glucose, fructose, sucrose, maltose, lactose, or starch and breast cancer incidence rate, and no association for glycemic index or glycemic load after adjusting for confounding factors. Intake of different carbohydrates was not associated with breast cancer incidence rates for either estrogen receptor positive (ER+) or (ER) breast cancer. Similarly, glycemic index and glycemic load were not associated with ER+ breast cancer after adjusting for confounding factors. A borderline significant positive association between glycemic index and (ER) breast cancer was observed (P = 0.05). In conclusion, we found no clear associations between intake of different carbohydrates, total carbohydrate intake, glycemic index, or glycemic load and breast cancer incidence in postmenopausal women. Furthermore, when ER+ and ER breast cancer cases were analyzed separately, no clear associations were observed. KEY WORDS: * breast cancer * carbohydrates * cohort study * estrogen receptor

Published
2005

138. Intake of whole grains and vegetables determines the plasma enterolactone concentration of Danish women

Author

Johnsen, Nina F., Hausner, Helene, Olsen, Anja, Tetens, Inge, Christensen, Jane, Knudsen, Knud Erik Bach, Overvad, Kim, and Tjonneland, Anne

Subjects
Digestion -- Research, Food/cooking/nutrition
Abstract

The mammalian lignan enterolactone (ENL), which is produced from dietary plant-lignan precursors by the intestinal microflora, may protect against breast cancer and other hormone-dependent cancers. This cross-sectional study examined which variables related to diet and lifestyle were associated with high plasma concentrations of ENL in Danish postmenopausal women. Plasma ENL was measured by time-resolved fluoroimmunoassay in 857 Danish women aged 50-64 y who participated in a prospective cohort study. Diet was assessed using a semiquantitative FFQ, and background information on lifestyle was collected using a self-administered questionnaire. Multiple analyses of covariance were completed in two steps. The median plasma ENL concentration was 27 nmol/L (range 0-455 nmol/L). In covariance analyses, positive associations were found between consumption of cereals, vegetables, and beverages and plasma ENL concentration. When analyzing subgroups of these food groups, the associations were confined to whole-grain products, cabbage, leafy vegetables, and coffee. For fat and the nondietary variables, negative associations between BMI, smoking, and frequency of bowel movements and plasma ENL concentration were observed. These data show that foods high in ENL precursors are associated with high concentrations of ENL. Furthermore, smoking, frequent bowel movements, and consumption of fat seems to have a negative affect on the ENL concentration. In conclusion, whole grains and vegetables are the most important dietary providers of plant lignans for the concentration of ENL in Danish postmenopausal women, and if ENL is found to protect against cancer or heart disease, the intake of whole grains and vegetables should be increased. KEY WORDS: * lignans * intestinal microflora * whole grains

Published
2004

139. Lifetime alcohol consumption and postmenopausal breast cancer rate in Denmark: a prospective cohort study

Author

Tjonneland, Anne, Christensen, Jane, Thomsen, Birthe L., Olsen, Anja, Stripp, Connie, Overvad, Kim, and Olsen, Jorgen H.

Subjects
Drinking of alcoholic beverages, Breast cancer, Food/cooking/nutrition
Abstract

Alcohol intake may be one of the few modifiable risk factors for breast cancer. In a prospective cohort of 29,875 women with 423 cases of breast cancer during 1993-2000, we examined the relationship between postmenopausal breast cancer incidence rate and alcohol consumption in different life periods. When alcohol intake during four age ranges, twenties, thirties, forties and fifties was evaluated, only the intake in the fifties increased the risk of breast cancer [rate ratio (RR) = 1.12 (95% CI: 1.05-1.19)] per 10 g/d increase in alcohol intake. After adjustment for intake at study entry, this association was no longer present [RR = 1.01 (95% CI: 0.91-1.13)]. The cumulative lifetime alcohol intake, adjusted for recent intake, showed no association with postmenopausal breast cancer risk. Recent alcohol intake, adjusted for the alcohol intake in the other life time periods, showed a significant association of RR = 1.09 (95% CI: 1.00-1.18) per 10 g/d. There was no indication of a higher risk among women with early drinking start, nor did women who started to drink before their first birth have a higher risk than women who started to drink later in life. Our results suggest that baseline intake of alcohol is a more important determinant of postmenopausal breast cancer risk than earlier lifetime exposure. KEY WORDS: * alcohol intake * lifetime * breast cancer

Published
2004

144. Fish intake is positively associated with breast cancer incidence rate

Author

Stripp, Connie, Overvad, Kim, Christensen, Jane, Thomsen, Birthe L., Olsen, Anja, Moller, Susanne, and Tjonneland, Anne

Subjects
Fish as food, Breast cancer -- Risk factors, Food/cooking/nutrition
Abstract

Animal studies have, in general, been supportive of a protective effect of fish and fish (n-3) PUFA against breast cancer risk; but the epidemiologic evidence of such a relationship is limited. Case-control and cohort studies have rarely shown significant associations. The association between total fish intake and the effect of fat content and preparation method of the fish, in relation to the incidence rate ratios of breast cancer, were investigated among postmenopausal women. We also investigated the effect of fish intake with respect to estrogen receptor expression of breast cancer tumors. A total of 23,693 postmenopausal women from the prospective study 'Diet, Cancer and Health' were included in the study. During follow-up, 424 women were diagnosed with breast cancer. The incidence rate ratio (IRR) and 95% CI per each additional 25 g of mean daily intake of fish were 1.13 (CI, 1.03-1.23). Analysis of fatty fish gave IRR of 1.11 (CI, 0.91-1.34), and the result for lean fish was 1.13 (CI, 0.99-1.29). When fish intake was stratified into three types of preparation methods, the IRR for fried fish was 1.09 (CI, 0.95-1.25), for boiled fish 1.09 (CI, 0.85-1.42), and for processed fish 1.12 (CI, 0.93-1.34). The IRR per additional 25 g of mean daily intake of fish was 1.14 (CI, 1.03-1.26) for estrogen receptor-positive (ER+) and 1.00 (CI, 0.81-1.24) for estrogen receptor-negative (ER-) breast cancer. In conclusion, this study showed that higher intakes of fish were significantly associated with higher incidence rates of breast cancer. The association was present only for development of ER+ breast cancer. KEY WORDS: * breast neoplasms * fish * estrogen receptors * cohort study

Published
2003

147. Contributors

Author

Alman, Benjamin A., primary, Arboleda, Valerie A., additional, Arnold, Andrew, additional, Bell, Graeme I., additional, Beckers, Albert M., additional, Bertagna, Xavier Y., additional, Bertherat, Jerome, additional, Christensen, Jane H., additional, Clément, Karine, additional, Cummings, Shelly A., additional, Daly, Adrian F., additional, Dittmar, Manuela, additional, Dreijerink, Koen M.A., additional, Dubern, Beatrice, additional, Dumitrescu, Alexandra, additional, Ehrmann, David A., additional, Ellard, Sian, additional, Evans, Douglas B., additional, Fagin, James A., additional, Fleming, Alice A., additional, Grasberger, Helmut, additional, Greeley, Siri A., additional, Groussin, Lionel, additional, Halsall, David J., additional, Hattersley, Andrew T., additional, Hoffman, Leslie, additional, Holick, Michael F., additional, Höppener, Jo W.M., additional, Hwa, Vivian, additional, Jimenez, Camilo, additional, Joseph, Loren, additional, Kahaly, George J., additional, Lauter, Kelly, additional, Layman, Lawrence C., additional, Libe, Rosella, additional, Lips, Cornelius J.M., additional, Van de Luijt, Rob B., additional, Mitsiades, Nicholas, additional, Murphy, Rinki, additional, van Nesselrooij, Bernadette P.M., additional, New, Maria I., additional, Nimkarn, Saroj, additional, O’Rahilly, Stephen, additional, Philipson, Louis H., additional, Pohlenz, Joachim, additional, Polonsky, Kenneth S., additional, Qin, Kenan, additional, Radovick, Sally, additional, Refetoff, Samuel, additional, Rich, Thereasa A., additional, Rittig, Soren, additional, Romero, Christopher J., additional, RosenfeLd, Ron G., additional, Savage, David B., additional, Semple, Robert K., additional, Stöy, Julie, additional, Stratakis, Constantine A., additional, Strauss, Bernard S., additional, Tounian, Patrick, additional, Vilain, Eric, additional, Vliet, Guy Van, additional, and Weiss, Roy E., additional

Published
2010
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