Abstract
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.
Original language | English |
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Pages (from-to) | 1286-1298 |
Number of pages | 13 |
Journal | Molecular Psychiatry |
Volume | 26 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 2021 |
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Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders. / Andlauer, Till F.M.; Guzman-Parra, Jose; Streit, Fabian; Strohmaier, Jana; González, Maria José; Gil Flores, Susana; Cabaleiro Fabeiro, Francisco J.; del Río Noriega, Francisco; Perez, Fermin Perez; Haro González, Jesus; Orozco Diaz, Guillermo; de Diego-Otero, Yolanda; Moreno-Küstner, Berta; Auburger, Georg; Degenhardt, Franziska; Heilmann-Heimbach, Stefanie; Herms, Stefan; Hoffmann, Per; Frank, Josef; Foo, Jerome C.; Treutlein, Jens; Witt, Stephanie H.; Cichon, Sven; Kogevinas, Manolis; Stahl, Eli A.; Breen, Gerome; Forstner, Andreas J.; McQuillin, Andrew; Ripke, Stephan; Trubetskoy, Vassily; Mattheisen, Manuel; Wang, Yunpeng; Coleman, Jonathan R.I.; Gaspar, Héléna A.; de Leeuw, Christiaan A.; Steinberg, Stacy; Pavlides, Jennifer M.Whitehead; Trzaskowski, Maciej; Pers, Tune H.; Holmans, Peter A.; Abbott, Liam; Agerbo, Esben; Akil, Huda; Albani, Diego; Alliey-Rodriguez, Ney; Als, Thomas D.; Anjorin, Adebayo; Antilla, Verneri; Awasthi, Swapnil; Badner, Judith A.; Bækvad-Hansen, Marie; Barchas, Jack D.; Bass, Nicholas; Bauer, Michael; Belliveau, Richard; Bergen, Sarah E.; Pedersen, Carsten Bøcker; Bøen, Erlend; Boks, Marco; Boocock, James; Budde, Monika; Bunney, William; Burmeister, Margit; Bybjerg-Grauholm, Jonas; Byerley, William; Casas, Miquel; Cerrato, Felecia; Cervantes, Pablo; Chambert, Kimberly; Charney, Alexander W.; Chen, Danfeng; Churchhouse, Claire; Clarke, Toni Kim; Coryell, William; Craig, David W.; Cruceanu, Cristiana; Czerski, Piotr M.; Dale, Anders M.; de Jong, Simone; Degenhardt, Franziska; Del-Favero, Jurgen; DePaulo, J. Raymond; Djurovic, Srdjan; Dobbyn, Amanda L.; Dumont, Ashley; Elvsåshagen, Torbjørn; Escott-Price, Valentina; Fan, Chun Chieh; Fischer, Sascha B.; Flickinger, Matthew; Foroud, Tatiana M.; Forty, Liz; Frank, Josef; Fraser, Christine; Freimer, Nelson B.; Frisén, Louise; Gade, Katrin; Gage, Diane; Garnham, Julie; Giambartolomei, Claudia; Pedersen, Marianne Giørtz; Goldstein, Jaqueline; Gordon, Scott D.; Gordon-Smith, Katherine; 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; Hipolito, Maria; Hoffmann, Per; Holland, Dominic; Huckins, Laura; Jamain, Stéphane; Johnson, Jessica S.; Juréus, Anders; Kandaswamy, Radhika; Karlsson, Robert; Kennedy, James L.; 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.; Levy, Shawn E.; Li, Jun Z.; Liu, Chunyu; Lucae, Susanne; Maaser, Anna; MacIntyre, Donald J.; Mahon, Pamela B.; Maier, Wolfgang; Martinsson, Lina; McCarroll, Steve; McGuffin, Peter; McInnis, Melvin G.; McKay, James D.; Medeiros, Helena; Medland, Sarah E.; Meng, Fan; Milani, Lili; Montgomery, Grant W.; Morris, Derek W.; 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.; 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; 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; Strauss, John S.; Streit, Fabian; Strohmaier, Jana; Szelinger, Szabolcs; Thompson, Robert C.; EThorgeirsson, Thorgeir; Treutlein, Jens; Vedde, Helmut; Wang, Weiqing; Watson, Stanley J.; Weickert, Thomas W.; Witt, Stephanie H.; Xi, Simon; Xu, Wei; Young, Allan H.; Zandi, Peter; Zhang, Peng; Zollner, Sebastian; Adolfsson, Rolf; Agartz, Ingrid; 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, Nick; Daly, Mark J.; Dannlowski, Udo; Esko, Tõnu; Etain, Bruno; Frye, Mark; Fullerton, Janice M.; Gershon, Elliot S.; Gill, Michael; Goes, Fernando S.; 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; 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; Mitchell, Philip B.; Morken, Gunnar; Mors, Ole; Mortensen, Preben Bo; Müller-Myhsok, Bertram; Myers, Richard M.; Neale, Benjamin M.; Nimgaonkar, Vishwajit; Nordentoft, Merete; Nöthen, Markus M.; 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.; Cichon, Sven; Ophoff, Roel A.; Scott, Laura J.; Andreassen, Ole A.; Kelsoe, John; Sklar, Pamela; Ripke, Stephan; Mattheisen, Manuel; Trzaskowski, Maciej; Byrne, Enda M.; 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; 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; 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.; Hoffmann, Per; Homuth, Georg; Horn, Carsten; Hottenga, Jouke Jan; Hougaard, David M.; Howard, David M.; Ising, Marcus; Jansen, Rick; Jorgenson, Eric; Knowles, James A.; Kohane, Isaac S.; Hill; 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; 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.; O’Reilly, Paul F.; Oskarsson, Hogni; Painter, Jodie N.; Pedersen, Carsten Bøcker; 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.; 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.; 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, André G.; Umbricht, Daniel; Van der Auwera, Sandra; 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; 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; 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.; Tiemeier, Henning; Uher, Rudolf; Völzke, Henry; Weissman, Myrna M.; Werge, Thomas; Levinson, Douglas F.; Børglum, Anders D.; Sullivan, Patrick F.; Rivas, Fabio; Mayoral, Fermín; Müller-Myhsok, Bertram; Forstner, Andreas J.; Nöthen, Markus M.; Rietschel, Marcella; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.
In: Molecular Psychiatry, Vol. 26, No. 4, 04.2021, p. 1286-1298.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders
AU - Andlauer, Till F.M.
AU - Guzman-Parra, Jose
AU - Streit, Fabian
AU - Strohmaier, Jana
AU - González, Maria José
AU - Gil Flores, Susana
AU - Cabaleiro Fabeiro, Francisco J.
AU - del Río Noriega, Francisco
AU - Perez, Fermin Perez
AU - Haro González, Jesus
AU - Orozco Diaz, Guillermo
AU - de Diego-Otero, Yolanda
AU - Moreno-Küstner, Berta
AU - Auburger, Georg
AU - Degenhardt, Franziska
AU - Heilmann-Heimbach, Stefanie
AU - Herms, Stefan
AU - Hoffmann, Per
AU - Frank, Josef
AU - Foo, Jerome C.
AU - Treutlein, Jens
AU - Witt, Stephanie H.
AU - Cichon, Sven
AU - Kogevinas, Manolis
AU - Stahl, Eli A.
AU - Breen, Gerome
AU - Forstner, Andreas J.
AU - McQuillin, Andrew
AU - Ripke, Stephan
AU - Trubetskoy, Vassily
AU - Mattheisen, Manuel
AU - Wang, Yunpeng
AU - Coleman, Jonathan R.I.
AU - Gaspar, Héléna A.
AU - de Leeuw, Christiaan A.
AU - Steinberg, Stacy
AU - Pavlides, Jennifer M.Whitehead
AU - Trzaskowski, Maciej
AU - Pers, Tune H.
AU - Holmans, Peter A.
AU - Abbott, Liam
AU - Agerbo, Esben
AU - Akil, Huda
AU - Albani, Diego
AU - Alliey-Rodriguez, Ney
AU - Als, Thomas D.
AU - Anjorin, Adebayo
AU - Antilla, Verneri
AU - Awasthi, Swapnil
AU - Badner, Judith A.
AU - Bækvad-Hansen, Marie
AU - Barchas, Jack D.
AU - Bass, Nicholas
AU - Bauer, Michael
AU - Belliveau, Richard
AU - Bergen, Sarah E.
AU - Pedersen, Carsten Bøcker
AU - Bøen, Erlend
AU - Boks, Marco
AU - Boocock, James
AU - Budde, Monika
AU - Bunney, William
AU - Burmeister, Margit
AU - Bybjerg-Grauholm, Jonas
AU - Byerley, William
AU - Casas, Miquel
AU - Cerrato, Felecia
AU - Cervantes, Pablo
AU - Chambert, Kimberly
AU - Charney, Alexander W.
AU - Chen, Danfeng
AU - Churchhouse, Claire
AU - Clarke, Toni Kim
AU - Coryell, William
AU - Craig, David W.
AU - Cruceanu, Cristiana
AU - Czerski, Piotr M.
AU - Dale, Anders M.
AU - de Jong, Simone
AU - Degenhardt, Franziska
AU - Del-Favero, Jurgen
AU - DePaulo, J. Raymond
AU - Djurovic, Srdjan
AU - Dobbyn, Amanda L.
AU - Dumont, Ashley
AU - Elvsåshagen, Torbjørn
AU - Escott-Price, Valentina
AU - Fan, Chun Chieh
AU - Fischer, Sascha B.
AU - Flickinger, Matthew
AU - Foroud, Tatiana M.
AU - Forty, Liz
AU - Frank, Josef
AU - Fraser, Christine
AU - Freimer, Nelson B.
AU - Frisén, Louise
AU - Gade, Katrin
AU - Gage, Diane
AU - Garnham, Julie
AU - Giambartolomei, Claudia
AU - Pedersen, Marianne Giørtz
AU - Goldstein, Jaqueline
AU - Gordon, Scott D.
AU - Gordon-Smith, Katherine
AU - Green, Elaine K.
AU - Green, Melissa J.
AU - Greenwood, Tiffany A.
AU - Grove, Jakob
AU - Guan, Weihua
AU - Parra, José Guzman
AU - Hamshere, Marian L.
AU - Hautzinger, Martin
AU - Heilbronner, Urs
AU - Herms, Stefan
AU - Hipolito, Maria
AU - Hoffmann, Per
AU - Holland, Dominic
AU - Huckins, Laura
AU - Jamain, Stéphane
AU - Johnson, Jessica S.
AU - Juréus, Anders
AU - Kandaswamy, Radhika
AU - Karlsson, Robert
AU - Kennedy, James L.
AU - Kittel-Schneider, Sarah
AU - Knowles, James A.
AU - Kogevinas, Manolis
AU - Koller, Anna C.
AU - Kupka, Ralph
AU - Lavebratt, Catharina
AU - Lawrence, Jacob
AU - Lawson, William B.
AU - Leber, Markus
AU - Lee, Phil H.
AU - Levy, Shawn E.
AU - Li, Jun Z.
AU - Liu, Chunyu
AU - Lucae, Susanne
AU - Maaser, Anna
AU - MacIntyre, Donald J.
AU - Mahon, Pamela B.
AU - Maier, Wolfgang
AU - Martinsson, Lina
AU - McCarroll, Steve
AU - McGuffin, Peter
AU - McInnis, Melvin G.
AU - McKay, James D.
AU - Medeiros, Helena
AU - Medland, Sarah E.
AU - Meng, Fan
AU - Milani, Lili
AU - Montgomery, Grant W.
AU - Morris, Derek W.
AU - Mühleisen, Thomas W.
AU - Mullins, Niamh
AU - Nguyen, Hoang
AU - Nievergelt, Caroline M.
AU - Adolfsson, Annelie Nordin
AU - Nwulia, Evaristus A.
AU - O’Donovan, Claire
AU - Loohuis, Loes M.Olde
AU - Ori, Anil P.S.
AU - Oruc, Lilijana
AU - Ösby, Urban
AU - Perlis, Roy H.
AU - Perry, Amy
AU - Pfennig, Andrea
AU - Potash, James B.
AU - Purcell, Shaun M.
AU - Regeer, Eline J.
AU - Reif, Andreas
AU - Reinbold, Céline S.
AU - Rice, John P.
AU - Richards, Alexander L.
AU - Rivas, Fabio
AU - Rivera, Margarita
AU - Roussos, Panos
AU - Ruderfer, Douglas M.
AU - Ryu, Euijung
AU - Sánchez-Mora, Cristina
AU - Schatzberg, Alan F.
AU - Scheftner, William A.
AU - Schork, Nicholas J.
AU - Weickert, Cynthia Shannon
AU - Shehktman, Tatyana
AU - Shilling, Paul D.
AU - Sigurdsson, Engilbert
AU - Slaney, Claire
AU - Smeland, Olav B.
AU - Sobell, Janet L.
AU - Hansen, Christine Søholm
AU - Spijker, Anne T.
AU - Clair, David St
AU - Steffens, Michael
AU - Strauss, John S.
AU - Streit, Fabian
AU - Strohmaier, Jana
AU - Szelinger, Szabolcs
AU - Thompson, Robert C.
AU - EThorgeirsson, Thorgeir
AU - Treutlein, Jens
AU - Vedde, Helmut
AU - Wang, Weiqing
AU - Watson, Stanley J.
AU - Weickert, Thomas W.
AU - Witt, Stephanie H.
AU - Xi, Simon
AU - Xu, Wei
AU - Young, Allan H.
AU - Zandi, Peter
AU - Zhang, Peng
AU - Zollner, Sebastian
AU - Adolfsson, Rolf
AU - Agartz, Ingrid
AU - Alda, Martin
AU - Backlund, Lena
AU - Baune, Bernhard T.
AU - Bellivier, Frank
AU - Berrettini, Wade H.
AU - Biernacka, Joanna M.
AU - Blackwood, Douglas H.R.
AU - Boehnke, Michael
AU - Børglum, Anders D.
AU - Corvin, Aiden
AU - Craddock, Nick
AU - Daly, Mark J.
AU - Dannlowski, Udo
AU - Esko, Tõnu
AU - Etain, Bruno
AU - Frye, Mark
AU - Fullerton, Janice M.
AU - Gershon, Elliot S.
AU - Gill, Michael
AU - Goes, Fernando S.
AU - Grigoroiu-Serbanescu, Maria
AU - Hauser, Joanna
AU - Hougaard, David M.
AU - Hultman, Christina M.
AU - Jones, Ian
AU - Jones, Lisa A.
AU - Kahn, René S.
AU - Kirov, George
AU - Landén, Mikael
AU - Leboyer, Marion
AU - Lewis, Cathryn M.
AU - Li, Qingqin S.
AU - Lissowska, Jolanta
AU - Martin, Nicholas G.
AU - Mayoral, Fermin
AU - McElroy, Susan L.
AU - McIntosh, Andrew M.
AU - McMahon, Francis J.
AU - Melle, Ingrid
AU - Metspalu, Andres
AU - Mitchell, Philip B.
AU - Morken, Gunnar
AU - Mors, Ole
AU - Mortensen, Preben Bo
AU - Müller-Myhsok, Bertram
AU - Myers, Richard M.
AU - Neale, Benjamin M.
AU - Nimgaonkar, Vishwajit
AU - Nordentoft, Merete
AU - Nöthen, Markus M.
AU - O’Donovan, Michael C.
AU - Oedegaard, Ketil J.
AU - Owen, Michael J.
AU - Paciga, Sara A.
AU - Pato, Carlos
AU - Pato, Michele T.
AU - Posthuma, Danielle
AU - Ramos-Quiroga, Josep Antoni
AU - Ribasés, Marta
AU - Rietschel, Marcella
AU - Rouleau, Guy A.
AU - Schalling, Martin
AU - Schofield, Peter R.
AU - Schulze, Thomas G.
AU - Serretti, Alessandro
AU - Smoller, Jordan W.
AU - Stefansson, Hreinn
AU - Stefansson, Kari
AU - Stordal, Eystein
AU - Sullivan, Patrick F.
AU - Turecki, Gustavo
AU - Vaaler, Arne E.
AU - Vieta, Eduard
AU - Vincent, John B.
AU - Werge, Thomas
AU - Nurnberger, John I.
AU - Wray, Naomi R.
AU - Florio, Arianna Di
AU - Edenberg, Howard J.
AU - Cichon, Sven
AU - Ophoff, Roel A.
AU - Scott, Laura J.
AU - Andreassen, Ole A.
AU - Kelsoe, John
AU - Sklar, Pamela
AU - Ripke, Stephan
AU - Mattheisen, Manuel
AU - Trzaskowski, Maciej
AU - Byrne, Enda M.
AU - Abdellaoui, Abdel
AU - Adams, Mark J.
AU - Agerbo, Esben
AU - Air, Tracy M.
AU - Bacanu, Silviu Alin
AU - Bækvad-Hansen, Marie
AU - Beekman, Aartjan T.F.
AU - Bigdeli, Tim B.
AU - Binder, Elisabeth B.
AU - Bryois, Julien
AU - Buttenschøn, Henriette N.
AU - Bybjerg-Grauholm, Jonas
AU - Cai, Na
AU - Castelao, Enrique
AU - Christensen, Jane Hvarregaard
AU - Clarke, Toni Kim
AU - Coleman, Jonathan R.I.
AU - Colodro-Conde, Lucía
AU - Couvy-Duchesne, Baptiste
AU - Craddock, Nick
AU - Crawford, Gregory E.
AU - Davies, Gail
AU - Deary, Ian J.
AU - Degenhardt, Franziska
AU - Derks, Eske M.
AU - Direk, Nese
AU - Dolan, Conor V.
AU - Dunn, Erin C.
AU - Eley, Thalia C.
AU - Escott-Price, Valentina
AU - Kiadeh, Farnush Farhadi Hassan
AU - Finucane, Hilary K.
AU - Foo, Jerome C.
AU - Forstner, Andreas J.
AU - Frank, Josef
AU - Gaspar, Héléna A.
AU - Gill, Michael
AU - Goes, Fernando S.
AU - Gordon, Scott D.
AU - Grove, Jakob
AU - Hall, Lynsey S.
AU - Hansen, Christine Søholm
AU - Hansen, Thomas F.
AU - Herms, Stefan
AU - Hickie, Ian B.
AU - Hoffmann, Per
AU - Homuth, Georg
AU - Horn, Carsten
AU - Hottenga, Jouke Jan
AU - Hougaard, David M.
AU - Howard, David M.
AU - Ising, Marcus
AU - Jansen, Rick
AU - Jorgenson, Eric
AU - Knowles, James A.
AU - Kohane, Isaac S.
AU - Hill,
AU - Kraft, Julia
AU - Kretzschmar, Warren W.
AU - Kutalik, Zoltán
AU - Li, Yihan
AU - Lind, Penelope A.
AU - MacIntyre, Donald J.
AU - MacKinnon, Dean F.
AU - Maier, Robert M.
AU - Maier, Wolfgang
AU - Marchini, Jonathan
AU - Mbarek, Hamdi
AU - McGrath, Patrick
AU - McGuffin, Peter
AU - Mehta, Divya
AU - Middeldorp, Christel M.
AU - Mihailov, Evelin
AU - Milaneschi, Yuri
AU - Milani, Lili
AU - Mondimore, Francis M.
AU - Montgomery, Grant W.
AU - Mostafavi, Sara
AU - Mullins, Niamh
AU - Nauck, Matthias
AU - Ng, Bernard
AU - Nivard, Michel G.
AU - Nyholt, Dale R.
AU - O’Reilly, Paul F.
AU - Oskarsson, Hogni
AU - Painter, Jodie N.
AU - Pedersen, Carsten Bøcker
AU - Pedersen, Marianne Giørtz
AU - Peterson, Roseann E.
AU - Pettersson, Erik
AU - Peyrot, Wouter J.
AU - Pistis, Giorgio
AU - Posthuma, Danielle
AU - Quiroz, Jorge A.
AU - Qvist, Per
AU - Rice, John P.
AU - Riley, Brien P.
AU - Rivera, Margarita
AU - Mirza, Saira Saeed
AU - Schoevers, Robert
AU - Schulte, Eva C.
AU - Shen, Ling
AU - Shi, Jianxin
AU - Shyn, Stanley I.
AU - Sigurdsson, Engilbert
AU - Sinnamon, Grant C.B.
AU - Smit, Johannes H.
AU - Smith, Daniel J.
AU - Steinberg, Stacy
AU - Streit, Fabian
AU - Strohmaier, Jana
AU - Tansey, Katherine E.
AU - Teismann, Henning
AU - Teumer, Alexander
AU - Thompson, Wesley
AU - Thomson, Pippa A.
AU - Thorgeirsson, Thorgeir E.
AU - Traylor, Matthew
AU - Treutlein, Jens
AU - Trubetskoy, Vassily
AU - Uitterlinden, André G.
AU - Umbricht, Daniel
AU - Van der Auwera, Sandra
AU - van Hemert, Albert M.
AU - Viktorin, Alexander
AU - Visscher, Peter M.
AU - Wang, Yunpeng
AU - Webb, Bradley T.
AU - Weinsheimer, Shantel Marie
AU - Wellmann, Jürgen
AU - Willemsen, Gonneke
AU - Witt, Stephanie H.
AU - Wu, Yang
AU - Xi, Hualin S.
AU - Yang, Jian
AU - Zhang, Futao
AU - Arolt, Volker
AU - Baune, Bernhard T.
AU - Berger, Klaus
AU - Boomsma, Dorret I.
AU - Cichon, Sven
AU - de Geus, E. J.C.
AU - DePaulo, J. Raymond
AU - Domenici, Enrico
AU - Domschke, Katharina
AU - Esko, Tõnu
AU - Grabe, Hans J.
AU - Hamilton, Steven P.
AU - Hayward, Caroline
AU - Heath, Andrew C.
AU - Kendler, Kenneth S.
AU - Kloiber, Stefan
AU - Lewis, Glyn
AU - Li, Qingqin S.
AU - Lucae, Susanne
AU - Madden, Pamela A.F.
AU - Magnusson, Patrik K.
AU - Martin, Nicholas G.
AU - McIntosh, Andrew M.
AU - Metspalu, Andres
AU - Mors, Ole
AU - Müller-Myhsok, Bertram
AU - Nordentoft, Merete
AU - Nöthen, Markus M.
AU - O’Donovan, Michael C.
AU - Paciga, Sara A.
AU - Pedersen, Nancy L.
AU - Penninx, Brenda W.J.H.
AU - Perlis, Roy H.
AU - Porteous, David J.
AU - Potash, James B.
AU - Preisig, Martin
AU - Rietschel, Marcella
AU - Schaefer, Catherine
AU - Schulze, Thomas G.
AU - Smoller, Jordan W.
AU - Tiemeier, Henning
AU - Uher, Rudolf
AU - Völzke, Henry
AU - Weissman, Myrna M.
AU - Werge, Thomas
AU - Levinson, Douglas F.
AU - Børglum, Anders D.
AU - Sullivan, Patrick F.
AU - Rivas, Fabio
AU - Mayoral, Fermín
AU - Müller-Myhsok, Bertram
AU - Forstner, Andreas J.
AU - Nöthen, Markus M.
AU - Rietschel, Marcella
AU - Bipolar Disorder Working Group of the Psychiatric Genomics Consortium
AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
N1 - Funding Information: Acknowledgements 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. Publisher Copyright: © 2019, The Author(s).
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85075169356&partnerID=8YFLogxK
U2 - 10.1038/s41380-019-0558-2
DO - 10.1038/s41380-019-0558-2
M3 - Article
C2 - 31712721
VL - 26
SP - 1286
EP - 1298
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
IS - 4
ER -