Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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31712721
TITLE
Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.
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.
DATE PUBLISHED
2019 Nov 11
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2018/08/21
accepted 2019/07/24
revised 2019/07/17
entrez 2019/11/13 06:00
pubmed 2019/11/13 06:00
medline 2019/11/13 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Andlauer TFM Andlauer Till F M TFM Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
Guzman-Parra J Guzman-Parra Jose J Department of Mental Health, University Regional Hospital of Málaga, Institute of Biomedicine of Málaga (IBIMA), Málaga, Spain.
Streit F Streit Fabian F Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Strohmaier J Strohmaier Jana J Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
González MJ González Maria José MJ Department of Mental Health, Hospital of Puerto Real, Cádiz, Spain.
Gil Flores S Gil Flores Susana S Department of Mental Health, University Hospital of Reina Sofia, Córdoba, Spain.
Cabaleiro Fabeiro FJ Cabaleiro Fabeiro Francisco J FJ Department of Mental Health, Hospital of Jaén, Jaén, Spain.
Del Río Noriega F Del Río Noriega Francisco F Department of Mental Health, Hospital of Jerez de la Frontera, Jerez de la Frontera, Spain.
Perez FP Perez Fermin Perez FP Department of Mental Health, Hospital of Puerto Real, Cádiz, Spain.
Haro González J Haro González Jesus J Department of Mental Health, Hospital Punta de Europa, Algeciras, Spain.
Orozco Diaz G Orozco Diaz Guillermo G Unidad de Gestión Clínica del Dispositivo de Cuidados Críticos y Urgencias del Distrito Sanitario Málaga-Coin-Guadalhorce, Málaga, Spain.
de Diego-Otero Y de Diego-Otero Yolanda Y Department of Mental Health, University Regional Hospital of Málaga, Institute of Biomedicine of Málaga (IBIMA), Málaga, Spain.
Moreno-Küstner B Moreno-Küstner Berta B Department of Personality, Assessment and Psychological Treatment, University of Malaga, Institute of Biomedicine of Málaga (IBIMA), Málaga, Spain.
Auburger G Auburger Georg G Department of Neurology, Goethe University Medical School, Frankfurt am Main, Germany.
Degenhardt F Degenhardt Franziska F Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Heilmann-Heimbach S Heilmann-Heimbach Stefanie S Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Herms S Herms Stefan S Department of Biomedicine, University of Basel, Basel, Switzerland.
Hoffmann P Hoffmann Per P Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, Germany.
Frank J Frank Josef J Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Foo JC Foo Jerome C JC Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Treutlein J Treutlein Jens J Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Witt SH Witt Stephanie H SH Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Cichon S Cichon Sven S Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, Germany.
Kogevinas M Kogevinas Manolis M Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain.
Bipolar Disorder Working Group of the Psychiatric Genomics Consortium
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Rivas F Rivas Fabio F Department of Mental Health, University Regional Hospital of Málaga, Institute of Biomedicine of Málaga (IBIMA), Málaga, Spain.
Mayoral F Mayoral Fermín F Department of Mental Health, University Regional Hospital of Málaga, Institute of Biomedicine of Málaga (IBIMA), Málaga, Spain.
Müller-Myhsok B Müller-Myhsok Bertram B Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Forstner AJ Forstner Andreas J AJ Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
Nöthen MM Nöthen Markus M MM Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Rietschel M Rietschel Marcella M Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Marcella.Rietschel@zi-mannheim.de.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Stahl Eli A EA
Breen Gerome G
Forstner Andreas J AJ
McQuillin Andrew A
Ripke Stephan S
Trubetskoy Vassily V
Mattheisen Manuel M
Wang Yunpeng Y
Coleman Jonathan R I JRI
Gaspar Héléna A HA
de Leeuw Christiaan A CA
Steinberg Stacy S
Pavlides Jennifer M Whitehead JMW
Trzaskowski Maciej M
Pers Tune H TH
Holmans Peter A PA
Abbott Liam L
Agerbo Esben E
Akil Huda H
Albani Diego D
Alliey-Rodriguez Ney N
Als Thomas D TD
Anjorin Adebayo A
Antilla Verneri V
Awasthi Swapnil S
Badner Judith A JA
Bækvad-Hansen Marie M
Barchas Jack D JD
Bass Nicholas N
Bauer Michael M
Belliveau Richard R
Bergen Sarah E SE
Pedersen Carsten Bøcker CB
Bøen Erlend E
Boks Marco M
Boocock James J
Budde Monika M
Bunney William W
Burmeister Margit M
Bybjerg-Grauholm Jonas J
Byerley William W
Casas Miquel M
Cerrato Felecia F
Cervantes Pablo P
Chambert Kimberly K
Charney Alexander W AW
Chen Danfeng D
Churchhouse Claire C
Clarke Toni-Kim TK
Coryell William W
Craig David W DW
Cruceanu Cristiana C
Czerski Piotr M PM
Dale Anders M AM
de Jong Simone S
Degenhardt Franziska F
Del-Favero Jurgen J
DePaulo J Raymond JR
Djurovic Srdjan S
Dobbyn Amanda L AL
Dumont Ashley A
Elvsåshagen Torbjørn T
Escott-Price Valentina V
Fan Chun Chieh CC
Fischer Sascha B SB
Flickinger Matthew M
Foroud Tatiana M TM
Forty Liz L
Frank Josef J
Fraser Christine C
Freimer Nelson B NB
Frisén Louise L
Gade Katrin K
Gage Diane D
Garnham Julie J
Giambartolomei Claudia C
Pedersen Marianne Giørtz MG
Goldstein Jaqueline J
Gordon Scott D SD
Gordon-Smith Katherine K
Green Elaine K EK
Green Melissa J MJ
Greenwood Tiffany A TA
Grove Jakob J
Guan Weihua W
Parra José Guzman JG
Hamshere Marian L ML
Hautzinger Martin M
Heilbronner Urs U
Herms Stefan S
Hipolito Maria M
Hoffmann Per P
Holland Dominic D
Huckins Laura L
Jamain Stéphane S
Johnson Jessica S JS
Juréus Anders A
Kandaswamy Radhika R
Karlsson Robert R
Kennedy James L JL
Kittel-Schneider Sarah S
Knowles James A JA
Kogevinas Manolis M
Koller Anna C AC
Kupka Ralph R
Lavebratt Catharina C
Lawrence Jacob J
Lawson William B WB
Leber Markus M
Lee Phil H PH
Levy Shawn E SE
Li Jun Z JZ
Liu Chunyu C
Lucae Susanne S
Maaser Anna A
MacIntyre Donald J DJ
Mahon Pamela B PB
Maier Wolfgang W
Martinsson Lina L
McCarroll Steve S
McGuffin Peter P
McInnis Melvin G MG
McKay James D JD
Medeiros Helena H
Medland Sarah E SE
Meng Fan F
Milani Lili L
Montgomery Grant W GW
Morris Derek W DW
Mühleisen Thomas W TW
Mullins Niamh N
Nguyen Hoang H
Nievergelt Caroline M CM
Adolfsson Annelie Nordin AN
Nwulia Evaristus A EA
O'Donovan Claire C
Loohuis Loes M Olde LMO
Ori Anil P S APS
Oruc Lilijana L
Ösby Urban U
Perlis Roy H RH
Perry Amy A
Pfennig Andrea A
Potash James B JB
Purcell Shaun M SM
Regeer Eline J EJ
Reif Andreas A
Reinbold Céline S CS
Rice John P JP
Richards Alexander L AL
Rivas Fabio F
Rivera Margarita M
Roussos Panos P
Ruderfer Douglas M DM
Ryu Euijung E
Sánchez-Mora Cristina C
Schatzberg Alan F AF
Scheftner William A WA
Schork Nicholas J NJ
Weickert Cynthia Shannon CS
Shehktman Tatyana T
Shilling Paul D PD
Sigurdsson Engilbert E
Slaney Claire C
Smeland Olav B OB
Sobell Janet L JL
Hansen Christine Søholm CS
Spijker Anne T AT
Clair David St DS
Steffens Michael M
Strauss John S JS
Streit Fabian F
Strohmaier Jana J
Szelinger Szabolcs S
Thompson Robert C RC
EThorgeirsson Thorgeir T
Treutlein Jens J
Vedde Helmut H
Wang Weiqing W
Watson Stanley J SJ
Weickert Thomas W TW
Witt Stephanie H SH
Xi Simon S
Xu Wei W
Young Allan H AH
Zandi Peter P
Zhang Peng P
Zollner Sebastian S
Adolfsson Rolf R
Agartz Ingrid I
Alda Martin M
Backlund Lena L
Baune Bernhard T BT
Bellivier Frank F
Berrettini Wade H WH
Biernacka Joanna M JM
Blackwood Douglas H R DHR
Boehnke Michael M
Børglum Anders D AD
Corvin Aiden A
Craddock Nicholas N
Daly Mark J MJ
Dannlowski Udo U
Esko Tõnu T
Etain Bruno B
Frye Mark M
Fullerton Janice M JM
Gershon Elliot S ES
Gill Michael M
Goes Fernando F
Grigoroiu-Serbanescu Maria M
Hauser Joanna J
Hougaard David M DM
Hultman Christina M CM
Jones Ian I
Jones Lisa A LA
Kahn René S RS
Kirov George G
Landén Mikael M
Leboyer Marion M
Lewis Cathryn M CM
Li Qingqin S QS
Lissowska Jolanta J
Martin Nicholas G NG
Mayoral Fermin F
McElroy Susan L SL
McIntosh Andrew M AM
McMahon Francis J FJ
Melle Ingrid I
Metspalu Andres A
Mitchell Philip B PB
Morken Gunnar G
Mors Ole O
Mortensen Preben Bo PB
Müller-Myhsok Bertram B
Myers Richard M RM
Neale Benjamin M BM
Nimgaonkar Vishwajit V
Nordentoft Merete M
Nöthen Markus M MM
O'Donovan Michael C MC
Oedegaard Ketil J KJ
Owen Michael J MJ
Paciga Sara A SA
Pato Carlos C
Pato Michele T MT
Posthuma Danielle D
Ramos-Quiroga Josep Antoni JA
Ribasés Marta M
Rietschel Marcella M
Rouleau Guy A GA
Schalling Martin M
Schofield Peter R PR
Schulze Thomas G TG
Serretti Alessandro A
Smoller Jordan W JW
Stefansson Hreinn H
Stefansson Kari K
Stordal Eystein E
Sullivan Patrick F PF
Turecki Gustavo G
Vaaler Arne E AE
Vieta Eduard E
Vincent John B JB
Werge Thomas T
Nurnberger John I JI
Wray Naomi R NR
Florio Arianna Di AD
Edenberg Howard J HJ
Cichon Sven S
Ophoff Roel A RA
Scott Laura J LJ
Andreassen Ole A OA
Kelsoe John J
Sklar Pamela P
Wray Naomi R NR
Ripke Stephan S
Mattheisen Manuel M
Trzaskowski Maciej M
Byrne Enda M EM
Abdellaoui Abdel A
Adams Mark J MJ
Agerbo Esben E
Air Tracy M TM
Andlauer Till F M TFM
Bacanu Silviu-Alin SA
Bækvad-Hansen Marie M
Beekman Aartjan T F ATF
Bigdeli Tim B TB
Binder Elisabeth B EB
Bryois Julien J
Buttenschøn Henriette N HN
Bybjerg-Grauholm Jonas J
Cai Na N
Castelao Enrique E
Christensen Jane Hvarregaard JH
Clarke Toni-Kim TK
Coleman Jonathan R I JRI
Colodro-Conde Lucía L
Couvy-Duchesne Baptiste B
Craddock Nick N
Crawford Gregory E GE
Davies Gail G
Deary Ian J IJ
Degenhardt Franziska F
Derks Eske M EM
Direk Nese N
Dolan Conor V CV
Dunn Erin C EC
Eley Thalia C TC
Escott-Price Valentina V
Kiadeh Farnush Farhadi Hassan FFH
Finucane Hilary K HK
Foo Jerome C JC
Forstner Andreas J AJ
Frank Josef J
Gaspar Héléna A HA
Gill Michael M
Goes Fernando S FS
Gordon Scott D SD
Grove Jakob J
Hall Lynsey S LS
Hansen Christine Søholm CS
Hansen Thomas F TF
Herms Stefan S
Hickie Ian B IB
Hoffmann Per P
Homuth Georg G
Horn Carsten C
Hottenga Jouke-Jan JJ
Hougaard David M DM
Howard David M DM
Ising Marcus M
Jansen Rick R
Jones Ian I
Jones Lisa A LA
Jorgenson Eric E
Knowles James A JA
Kohane Isaac S IS
Kraft Julia J
Kretzschmar Warren W WW
Kutalik Zoltán Z
Li Yihan Y
Lind Penelope A PA
MacIntyre Donald J DJ
MacKinnon Dean F DF
Maier Robert M RM
Maier Wolfgang W
Marchini Jonathan J
Mbarek Hamdi H
McGrath Patrick P
McGuffin Peter P
Medland Sarah E SE
Mehta Divya D
Middeldorp Christel M CM
Mihailov Evelin E
Milaneschi Yuri Y
Milani Lili L
Mondimore Francis M FM
Montgomery Grant W GW
Mostafavi Sara S
Mullins Niamh N
Nauck Matthias M
Ng Bernard B
Nivard Michel G MG
Nyholt Dale R DR
O'Reilly Paul F PF
Oskarsson Hogni H
Owen Michael J MJ
Painter Jodie N JN
Pedersen Carsten Bøcker CB
Pedersen Marianne Giørtz MG
Peterson Roseann E RE
Pettersson Erik E
Peyrot Wouter J WJ
Pistis Giorgio G
Posthuma Danielle D
Quiroz Jorge A JA
Qvist Per P
Rice John P JP
Riley Brien P BP
Rivera Margarita M
Mirza Saira Saeed SS
Schoevers Robert R
Schulte Eva C EC
Shen Ling L
Shi Jianxin J
Shyn Stanley I SI
Sigurdsson Engilbert E
Sinnamon Grant C B GCB
Smit Johannes H JH
Smith Daniel J DJ
Stefansson Hreinn H
Steinberg Stacy S
Streit Fabian F
Strohmaier Jana J
Tansey Katherine E KE
Teismann Henning H
Teumer Alexander A
Thompson Wesley W
Thomson Pippa A PA
Thorgeirsson Thorgeir E TE
Traylor Matthew M
Treutlein Jens J
Trubetskoy Vassily V
Uitterlinden André G AG
Umbricht Daniel D
Van der Auwera Sandra S
van Hemert Albert M AM
Viktorin Alexander A
Visscher Peter M PM
Wang Yunpeng Y
Webb Bradley T BT
Weinsheimer Shantel Marie SM
Wellmann Jürgen J
Willemsen Gonneke G
Witt Stephanie H SH
Wu Yang Y
Xi Hualin S HS
Yang Jian J
Zhang Futao F
Arolt Volker V
Baune Bernhard T BT
Berger Klaus K
Boomsma Dorret I DI
Cichon Sven S
Dannlowski Udo U
de Geus E J C EJC
DePaulo J Raymond JR
Domenici Enrico E
Domschke Katharina K
Esko Tõnu T
Grabe Hans J HJ
Hamilton Steven P SP
Hayward Caroline C
Heath Andrew C AC
Kendler Kenneth S KS
Kloiber Stefan S
Lewis Glyn G
Li Qingqin S QS
Lucae Susanne S
Madden Pamela A F PAF
Magnusson Patrik K PK
Martin Nicholas G NG
McIntosh Andrew M AM
Metspalu Andres A
Mors Ole O
Mortensen Preben Bo PB
Müller-Myhsok Bertram B
Nordentoft Merete M
Nöthen Markus M MM
O'Donovan Michael C MC
Paciga Sara A SA
Pedersen Nancy L NL
Penninx Brenda W J H BWJH
Perlis Roy H RH
Porteous David J DJ
Potash James B JB
Preisig Martin M
Rietschel Marcella M
Schaefer Catherine C
Schulze Thomas G TG
Smoller Jordan W JW
Stefansson Kari K
Tiemeier Henning H
Uher Rudolf R
Völzke Henry H
Weissman Myrna M MM
Werge Thomas T
Lewis Cathryn M CM
Levinson Douglas F DF
Breen Gerome G
Børglum Anders D AD
Sullivan Patrick F PF
JOURNAL
VOLUME:
ISSUE:
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2019
MONTH: Nov
DAY: 11
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
RI908/11-1 Deutsche Forschungsgemeinschaft (German Research Foundation)
MU1315/8-2 Deutsche Forschungsgemeinschaft (German Research Foundation)
NO246/10-1 Deutsche Forschungsgemeinschaft (German Research Foundation)
156791 Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
GENERAL NOTE
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