Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations
Autor: | Van Hemert, Albert M., Porteous, David J., O'Donovan, Michael C., McIntosh, Andrew M., Lewis, Glyn, Hayward, Caroline, Traylor, Matthew, Thomson, Pippa A., Tansey, Katherine E., Smith, Daniel J., Owen, Michael J., O'Reilly, Paul F., McGuffin, Peter, Marchini, Jonathan, MacIntyre, Donald J., Kretzschmar, Warren W., Hall, Lynsey S., Gaspar, Helena A., Escott-Price, Valentina, Eley, Thalia C., Deary, Ian J., Davies, Gail, Craddock, Nick, Coleman, Jonathan R.I., Clarke, Toni-Kim, Cai, Na, Blackwood, Douglas H.R., Adams, Mark J., Rivera, Margarita, Mullins, Niamh, Lewis, Cathryn, Kan, Carol, Dehghan, Abbas, Breen, Gerome, Sullivan, Patrick F., Borglum, Anders D., Levinson, Douglas F., Werge, Thomas, Weissman, Myrna M., Volzke, Henry, Uher, Rudolf, Tiemeier, Henning, Stefansson, Kari, Smoller, Jordan W., Schulze, Thomas G., Schaefer, Catherine, Potash, James B., Trubetskoy, Vassily, Treutlein, Jens, Thorgeirsson, Thorgeir E., Thompson, Wesley, Teismann, Henning, Steinberg, Stacy, Stefansson, Hreinn, Smit, Johannes H., Sinnamon, Grant C.B., Sigurdsson, Engilbert, Shyn, Stanley I., Shi, Jianxin, Shen, Ling, Schulte, Eva C., Schoevers, Robert, Mirza, Saira Saeed, Riley, Brien P., Rice, John P., Qvist, Per, Quiroz, Jorge A., Posthuma, Danielle, Pettersson, Erik, Peterson, Roseann E., Pedersen, Marianne Giortz, Pedersen, Carsten Bocker, Painter, Jodie N., Oskarsson, Hogni, Nyholt, Dale R., Nivard, Michel G., Ng, Bernard, Mostafavi, Sara, Montgomery, Grant W., Mondimore, Francis M., Milani, Lili, Mihailov, Evelin, Middeldorp, Christel M., Mehta, Divya, Medland, Sarah E., McGrath, Patrick, Mbarek, Hamdi, Maier, Wolfgang, Maier, Robert M., MacKinnon, Dean F., Lind, Penelope A., Li, Yihan, Kutalik, Zoltan, Krogh, Jesper, Kraft, Julia, Kohane, Isaac S., Knowles, James A., Jorgenson, Eric, Jansen, Rick, Ising, Marcus, Hougaard, David M., Hottenga, Jouke-Jan, Horn, Carsten, Hoffmann, Per, Hickie, Ian B., Herms, Stefan, Hansen, Thomas F., Hansen, Christine Soholm, Grove, Jakob, Gordon, Scott D., Goes, Fernando S., Frank, Josef, Finucane, Hilary K., Kiadeh, Farnush Farhadi Hassan, Dunn, Erin C., Dolan, Conor V., Direk, Nese, Derks, Eske M., Degenhardt, Franziska, Crawford, Gregory E., Couvy-Duchesne, Baptiste, Colodro-Conde, Lucia, Christensen, Jane Hvarregaard, Castelao, Enrique, Bybjerg-Grauholm, Jonas, Buttenschon, Henriette N., Bryois, Julien, Bigdeli, Tim B., Beekman, Aartjan T.F., Bakvad-Hansen, Marie, Bacanu, Silviu-Alin, Andlauer, Till F.M., Air, Tracy M., Agerbo, Esben, Abdellaoui, Abdel, Byrne, Enda M., Mattheisen, Manuel, Ripke, Stephan, Penninx, Brenda W.J.H., Boomsma, Dorret I., Wray, Naomi R., Van Der Auwera, Sandra, Teumer, Alexander, Strohmaier, Jana, Streit, Fabian, Rietschel, Marcella, Preisig, Martin, Pistis, Giorgio, Nauck, Matthias, Homuth, Georg, Grabe, Hans J., Forstner, Andreas J., Baune, Bernhard T., Peyrot, Wouter J., Lamers, Femke, Milaneschi, Yuri, Gill, Michael, Binder, Elisabeth B., Trzaskowski, Maciej, Perlis, Roy H., Pedersen, Nancy L., Paciga, Sara A., Nothen, Markus M., Nordentoft, Merete, Muller-Myhsok, Bertram, Mortensen, Preben Bo, Mors, Ole, Metspalu, Andres, Martin, Nicholas G., Magnusson, Patrik K., Madden, Pamela A.F., Lucae, Susanne, Li, Qingqin S., Kloiber, Stefan, Kendler, Kenneth S., Heath, Andrew C., Hamilton, Steven P., Esko, Tonu, Domschke, Katharina, Domenici, Enrico, DePaulo, J. Raymond, De Geus, E.J.C., Dannlowski, Udo, Cichon, Sven, Arolt, Volker, Zhang, Futao, Yang, Jian, Xi, Hualin S., Wu, Yang, Witt, Stephanie H., Willemsen, Gonneke, Wellmann, Jurgen, Weinsheimer, Shantel Marie, Webb, Bradley T., Wang, Yunpeng, Visscher, Peter M., Viktorin, Alexander, Umbricht, Daniel, Uitterlinden, Andre G., Berger, Klaus |
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Přispěvatelé: | Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Psychiatry, APH - Digital Health, Biological Psychology, Clinical Psychology, APH - Methodology, Epidemiology, Urology, Child and Adolescent Psychiatry / Psychology, Internal Medicine, Medical Informatics, Immunology |
Rok vydání: | 2017 |
Předmět: |
Netherlands Twin Register (NTR)
Adult Male medicine.medical_specialty International Cooperation Population Genome-wide association study Overweight Weight Gain behavioral disciplines and activities Body Mass Index 03 medical and health sciences 0302 clinical medicine SDG 3 - Good Health and Well-being Internal medicine mental disorders medicine Journal Article Humans Genetic Predisposition to Disease Obesity Psychiatry education Problem Solving Depression (differential diagnoses) Original Investigation Craving Psychiatric Status Rating Scales education.field_of_study Depressive Disorder Major Odds ratio medicine.disease 030227 psychiatry Multicenter Study Diagnostic and Statistical Manual of Mental Disorders Psychiatry and Mental health C-Reactive Protein Cohort Major depressive disorder Female medicine.symptom Psychology Body mass index 030217 neurology & neurosurgery Genome-Wide Association Study |
Zdroj: | Milaneschi, Y, Lamers, F, Peyrot, W J, Baune, B T, Breen, G, Dehghan, A, Forstner, A J, Grabe, H J, Homuth, G, Kan, C, Lewis, C, Mullins, N, Nauck, M, Pistis, G, Preisig, M, Rivera, M, Rietschel, M, Streit, F, Strohmaier, J, Teumer, A, Van der Auwera, S, Wray, N R, Boomsma, D I, Penninx, B W J H & CHARGE Inflammation Working Group and the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2017, ' Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations ', J A M A Psychiatry, vol. 74, no. 12, pp. 1214-1225 . https://doi.org/10.1001/jamapsychiatry.2017.3016 Milaneschi, Y, Lamers, F, Peyrot, W J, Baune, B T, Breen, G, Dehghan, A, Forstner, A J, Grabe, H J, Homuth, G, Kan, C, Lewis, C, Mullins, N, Nauck, M, Pistis, G, Preisig, M, Rivera, M, Rietschel, M, Streit, F, Strohmaier, J, Teumer, A, Van der Auwera, S, Wray, N R, Boomsma, D I, Penninx, B W J H & CHARGE Inflammation Working Group and the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2017, ' Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations ', JAMA Psychiatry, vol. 74, no. 12, pp. 1214-1225 . https://doi.org/10.1001/jamapsychiatry.2017.3016 JAMA psychiatry 2017, ' Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations ', JAMA Psychiatry . https://doi.org/10.1001/jamapsychiatry.2017.3016 JAMA Psychiatry, 74(12), 1214-1225. American Medical Association Milaneschi, Y, Lamers, F, Peyrot, W J, Baune, B T, Breen, G, Dehghan, A, Forstner, A J, Grabe, H J, Homuth, G, Kan, C, Lewis, C M, Mullins, N, Nauck, M, Pistis, G, Preisig, M, Rivera, M, Rietschel, M, Streit, F, Strohmaier, J, Teumer, A, Van der Auwera, S, Wray, N R, Boomsma, D I, Penninx, B W J H & CHARGE Inflammation Working Group and the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2017, ' Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations ', JAMA Psychiatry, vol. 74, no. 12, pp. 1214-1225 . https://doi.org/10.1001/jamapsychiatry.2017.3016 |
ISSN: | 2168-6238 2168-622X |
Popis: | © 2017 American Medical Association. All rights reserved.IMPORTANCE The association between major depressive disorder (MDD) and obesitymay stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased appetite and/or weight (A/W) during an active episode. OBJECTIVE To determine whether subgroups of patients with MDD stratified according to the A/W criterion had a different degree of genetic overlap with obesity-related traits (body mass index [BMI] and levels of C-reactive protein [CRP] and leptin). DESIGN, SETTING, AND PATIENTS This multicenter study assembled genome-wide genotypic and phenotypic measures from 14 data sets of the Psychiatric Genomics Consortium. Data sets were drawn from case-control, cohort, and population-based studies, including 26 628 participants with established psychiatric diagnoses and genome-wide genotype data. Data on BMI were available for 15 237 participants. Data were retrieved and analyzed from September 28, 2015, through May 20, 2017. MAIN OUTCOMES AND MEASURES Lifetime DSM-IV MDDwas diagnosed using structured diagnostic instruments. Patients with MDD were stratified into subgroups according to change in the DSM-IV A/W symptoms as decreased or increased. RESULTS Data included 11 837 participants with MDD and 14 791 control individuals, for a total of 26 628 participants (59.1% female and 40.9%male). Among participants with MDD, 5347 (45.2%) were classified in the decreased A/W and 1871 (15.8%) in the increased A/W subgroups. Common genetic variants explained approximately 10% of the heritability in the 2 subgroups. The increased A/W subgroup showed a strong and positive genetic correlation (SE) with BMI (0.53 [0.15]; P = 6.3 × 10-4), whereas the decreased A/W subgroup showed an inverse correlation (-0.28 [0.14]; P = .06). Furthermore, the decreased A/W subgroup had a higher polygenic risk for increased BMI (odds ratio [OR], 1.18; 95%CI, 1.12-1.25; P = 1.6 × 10-10) and levels of CRP (OR, 1.08; 95%CI, 1.02-1.13; P = 7.3 × 10-3) and leptin (OR, 1.09; 95%CI, 1.06-1.12; P = 1.7 × 10-3). CONCLUSIONS AND RELEVANCE The phenotypic associations between atypical depressive symptoms and obesity-related traits may arise from shared pathophysiologic mechanisms in patients with MDD. Development of treatments effectively targeting immunometabolic dysregulations may benefit patients with depression and obesity, both syndromes with important disability. |
Databáze: | OpenAIRE |
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