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1. Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.

Author

Andlauer, Till FM, 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, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Rivas, Fabio, Mayoral, Fermín, Müller-Myhsok, Bertram, Forstner, Andreas J, Nöthen, Markus M, and Rietschel, Marcella

Subjects
Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Psychiatry, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences
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.

Published
2021

2. The Andalusian Bipolar Family (ABiF) Study: Protocol and sample description

Author

Guzman-Parra, Jose, Rivas, Fabio, Strohmaier, Jana, Forstner, Andreas, Streit, Fabian, Auburger, Georg, Propping, Peter, Orozco-Diaz, Guillermo, González, Maria José, Gil-Flores, Susana, Cabaleiro-Fabeiro, Francisco Javier, del Río-Noriega, Francisco, Perez-Perez, Fermin, Haro-González, Jesus, de Diego-Otero, Yolanda, Romero-Sanchiz, Pablo, Moreno-Küstner, Berta, Cichon, Sven, Nöthen, Markus M., Rietschel, Marcella, and Mayoral, Fermin

Published
2018
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3. El estudio Andalusian Bipolar Family (ABiF): protocolo y descripción de la muestra

Author

Guzman-Parra, Jose, Rivas, Fabio, Strohmaier, Jana, Forstner, Andreas, Streit, Fabian, Auburger, Georg, Propping, Peter, Orozco-Diaz, Guillermo, González, Maria José, Gil-Flores, Susana, Cabaleiro-Fabeiro, Francisco Javier, del Río-Noriega, Francisco, Perez-Perez, Fermin, Haro-González, Jesus, de Diego-Otero, Yolanda, Romero-Sanchiz, Pablo, Moreno-Küstner, Berta, Cichon, Sven, Nöthen, Markus M., Rietschel, Marcella, and Mayoral, Fermin

Published
2018
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4. Clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex families

Author

Guzman-Parra, Jose, Streit, Fabian, Forstner, Andreas J., Strohmaier, Jana, González, Maria José, Gil Flores, Susana, Cabaleiro Fabeiro, Francisco J., del Río Noriega, Francisco, Perez Perez, Fermin, Haro González, Jesus, Orozco Diaz, Guillermo, de Diego-Otero, Yolanda, Moreno-Kustner, Berta, Auburger, Georg, Degenhardt, Franziska, Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoffmann, Per, Frank, Josef, Foo, Jerome C., Sirignano, Lea, Witt, Stephanie H., Cichon, Sven, Rivas, Fabio, Mayoral, Fermín, Nöthen, Markus M., Andlauer, Till F. M., and Rietschel, Marcella

Published
2021
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5. Whole-exome sequencing of 81 individuals from 27 multiply affected bipolar disorder families

Author

Forstner, Andreas J., Fischer, Sascha B., Schenk, Lorena M., Strohmaier, Jana, Maaser-Hecker, Anna, Reinbold, Céline S., Sivalingam, Sugirthan, Hecker, Julian, Streit, Fabian, Degenhardt, Franziska, Witt, Stephanie H., Schumacher, Johannes, Thiele, Holger, Nürnberg, Peter, Guzman-Parra, José, Orozco Diaz, Guillermo, Auburger, Georg, Albus, Margot, Borrmann-Hassenbach, Margitta, González, Maria José, Gil Flores, Susana, Cabaleiro Fabeiro, Francisco J., del Río Noriega, Francisco, Perez Perez, Fermin, Haro González, Jesus, Rivas, Fabio, Mayoral, Fermin, Bauer, Michael, Pfennig, Andrea, Reif, Andreas, Herms, Stefan, Hoffmann, Per, Pirooznia, Mehdi, Goes, Fernando S., Rietschel, Marcella, Nöthen, Markus M., and Cichon, Sven

Published
2020
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6. Clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex families

Author

Guzman-Parra, Jose, Streit, Fabian, Forstner, Andreas J., Strohmaier, Jana, González, Maria José, Gil Flores, Susana, Cabaleiro Fabeiro, Francisco J., del Río Noriega, Francisco, Perez Perez, Fermin, Haro González, Jesus, Orozco Diaz, Guillermo, de Diego-Otero, Yolanda, Moreno-Kustner, Berta, Auburger, Georg, Degenhardt, Franziska, Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoffmann, Per, Frank, Josef, Foo, Jerome C., Sirignano, Lea, Witt, Stephanie H., Cichon, Sven, Rivas, Fabio, Mayoral, Fermín, Nöthen, Markus M., Andlauer, Till F. M., and Rietschel, Marcella

Subjects
Article, Bipolar disorder, Clinical genetics, ddc
Published
2020

7. Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

Author

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, 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, 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, Hipolito, Maria, Holland, Dominic, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S., Juréus, Anders, Kandaswamy, Radhika, Karlsson, Robert, Kennedy, James L., Kittel-Schneider, Sarah, Knowles, James A., 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., Szelinger, Szabolcs, Thompson, Robert C., EThorgeirsson, Thorgeir, Vedde, Helmut, Wang, Weiqing, Watson, Stanley J., Weickert, Thomas W., 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, Nicholas, Daly, Mark J., Dannlowski, Udo, Esko, Tõnu, Etain, Bruno, Frye, Mark, Fullerton, Janice M., Gill, Michael, Martin, Nicholas G., Schofield, Peter R., Sullivan, Patrick F., Adams, Mark J., Colodro-Conde, Lucía, Derks, Eske M., Howard, David M., Lind, Penelope A., Mehta, Divya, Nyholt, Dale R., Smith, Daniel J., Visscher, Peter M., other, and, 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, 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, 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, Hipolito, Maria, Holland, Dominic, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S., Juréus, Anders, Kandaswamy, Radhika, Karlsson, Robert, Kennedy, James L., Kittel-Schneider, Sarah, Knowles, James A., 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., Szelinger, Szabolcs, Thompson, Robert C., EThorgeirsson, Thorgeir, Vedde, Helmut, Wang, Weiqing, Watson, Stanley J., Weickert, Thomas W., 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, Nicholas, Daly, Mark J., Dannlowski, Udo, Esko, Tõnu, Etain, Bruno, Frye, Mark, Fullerton, Janice M., Gill, Michael, Martin, Nicholas G., Schofield, Peter R., Sullivan, Patrick F., Adams, Mark J., Colodro-Conde, Lucía, Derks, Eske M., Howard, David M., Lind, Penelope A., Mehta, Divya, Nyholt, Dale R., Smith, Daniel J., Visscher, Peter M., and other, and

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.

Published
2021

8. El estudio Andalusian Bipolar Family(ABiF): protocolo y descripción de la muestra

Author

Guzman-Parra, Jose, Rivas, Fabio, Strohmaier, Jana, Forstner, Andreas, Streit, Fabian, Auburger, Georg, Propping, Peter, Orozco-Diaz, Guillermo, González, Maria José, Gil-Flores, Susana, Cabaleiro-Fabeiro, Francisco Javier, del Río-Noriega, Francisco, Perez-Perez, Fermin, Haro-González, Jesus, de Diego-Otero, Yolanda, Romero-Sanchiz, Pablo, Moreno-Küstner, Berta, Cichon, Sven, Nöthen, Markus M., Rietschel, Marcella, and Mayoral, Fermin

Abstract

Se presenta la primera descripción del estudio denominado Andalusian Bipolar Family(ABiF). Se trata de una investigación longitudinal con familias procedentes de Andalucía (España), que comenzó en 1997, con el objetivo de dilucidar las causas geneticomoleculares del trastorno afectivo bipolar. Desde entonces, esta cohorte ha contribuido a una serie de hallazgos clave, que han sido publicados en revistas internacionales. Sin embargo, el conocimiento sobre las bases genéticas del trastorno en estas familias sigue siendo limitado.

Published
2018
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9. Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

Author

Andlauer, Till FM, 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, Bipolar Disorder Working Group Of The Psychiatric Genomics Consortium, Consortium, Major Depressive Disorder Working Group Of The Psychiatric Genomics, Rivas, Fabio, Mayoral, Fermín, Müller-Myhsok, Bertram, Forstner, Andreas J, Nöthen, Markus M, and Rietschel, Marcella

Subjects
Depressive Disorder, Major, Bipolar Disorder, Case-Control Studies, Schizophrenia, Humans, Genetic Predisposition to Disease, 3. Good health
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.

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