Age at first birth in women is genetically associated with increased risk of schizophrenia

• Main Authors: Ni, G. (Guiyan), Gratten, J. (Jacob), Wray, N. R. (Naomi R.), Lee, S. H. (Sang Hong), S. W. (Schizophrenia Working Group of the Psychiatric Genomics Consortium)
• Format: Article in Journal/Newspaper
• Language: English
• Published: Springer Nature 2018
• Subjects: Brisbane; Brockton; Canada; Castle Peak; Chapel Hill; Ditte; Draga; Jebsen; Jeremy; Kari; Kung; Marian; Norway; Olli; Orleans; Pablo; Queensland; Rouen; SalpÊtriÈre; St. Louis; Stacy; Sven; Sørlandet; Tbilisi; Todd; Valentina; Iceland
• Online Access: http://urn.fi/urn:nbn:fi-fe2018111448098

Abstract Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is −0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health. Consortia Schizophrenia Working Group of the Psychiatric Genomics Consortium Stephan Ripke5,6, Benjamin M. Neale5,6,7,8, Aiden Corvin9, James T. R. Walters10, Kai-How Farh5, Peter A. Holmans10,11, Phil Lee5,6,8, Brendan Bulik-Sullivan5,6, David A. Collier12,13, Hailiang Huang5,7, Tune H. Pers7,14,15, Ingrid Agartz16,17,18, Esben Agerbo19,20,21, Margot Albus22, Madeline Alexander23, Farooq Amin24,25, Silviu A. Bacanu26, Martin Begemann27, Richard A. Belliveau6, Judit Bene28,29, Sarah E. Bergen6,30, Elizabeth Bevilacqua6, Tim B. Bigdeli26, Donald W. Black31, Richard Bruggeman32, Nancy G. Buccola33, Randy L. Buckner34,35,36, William Byerley37, Wiepke Cahn38, Guiqing Cai39,40, Dominique Campion41, Rita M. Cantor42, Vaughan J. Carr43,44, Noa Carrera10, Stanley V. Catts43,45, Kimberly D. Chambert6, Raymond C. K. Chan46, Ronald Y. L. Chen47, Eric Y. H. Chen47,48, Wei Cheng49, Eric F. C. Cheung50, Siow Ann Chong51, C. Robert Cloninger52, David Cohen53, Nadine Cohen54, Paul Cormican9, Nick Craddock10,11, James J. Crowley55, David Curtis56,57, Michael Davidson58, Kenneth L. Davis40, Franziska Degenhardt59,60, Jurgen Del Favero61, Ditte Demontis21,62,63, Dimitris Dikeos64, Timothy Dinan65, Srdjan Djurovic18,66, Gary Donohoe9,67, Elodie Drapeau40, Jubao Duan68,69, Frank Dudbridge70, Naser Durmishi71, Peter Eichhammer72, Johan Eriksson73,74,75, Valentina Escott-Price10, Laurent Essioux76, Ayman H. Fanous77,78,79,80, Martilias S. Farrell55, Josef Frank81, Lude Franke82, Robert Freedman83, Nelson B. Freimer84, Marion Friedl85, Joseph I. Friedman40, Menachem Fromer5,6,8,86, Giulio Genovese6, Lyudmila Georgieva10, Ina Giegling85,87, Paola Giusti-Rodríguez55, Stephanie Godard88, Jacqueline I. Goldstein5,7, Vera Golimbet89, Srihari Gopal90, Lieuwe de Haan91, Christian Hammer27, Marian L. Hamshere10, Mark Hansen92, Thomas Hansen21,93, Vahram Haroutunian40,94,95, Annette M. Hartmann85, Frans A. Henskens43,96,97, Stefan Herms59,60,98, Joel N. Hirschhorn7,15,99, Per Hoffmann59,60,98, Andrea Hofman59,60, Mads V. Hollegaard100, David M. Hougaard100, Masashi Ikeda101, Inge Joa102, Antonio Juliá103, René S. Kahn38, Luba Kalaydjieva104,105, Sena Karachanak-Yankova106, Juha Karjalainen82, David Kavanagh10, Matthew C. Keller107, James L. Kennedy108,109,110, Andrey Khrunin111, Yunjung Kim55, Janis Klovins112, James A. Knowles113, Bettina Konte85, Vaidutis Kucinskas114, Zita Ausrele Kucinskiene114, Hana Kuzelova-Ptackova115, Anna K. Kähler30, Claudine Laurent23,116, Jimmy Lee Chee Keong51,117, Sophie E. Legge10, Bernard Lerer118, Miaoxin Li47,48,119, Tao Li120, Kung-Yee Liang121, Jeffrey Lieberman122, Svetlana Limborska111, Carmel M. Loughland43,123, Jan Lubinski124, Jouko Lönnqvist125, Milan Macek115, Patrik K. E. Magnusson30, Brion S. Maher126, Wolfgang Maier127, Jacques Mallet128, Sara Marsal103, Manuel Mattheisen21,62,63,129, Morten Mattingsdal18,130, Robert W. McCarley131,132, Colm McDonald133, Andrew M. McIntosh134,135, Sandra Meier81, Carin J. Meijer91, Bela Melegh28,29, Ingrid Melle18,136, Raquelle I. Mesholam-Gately131,137, Andres Metspalu138, Patricia T. Michie43,139, Lili Milani138, Vihra Milanova140, Younes Mokrab12, Derek W. Morris9,67, Ole Mors21,62,141, Kieran C. Murphy142, Robin M. Murray143, Inez Myin-Germeys144, Bertram Müller-Myhsok145,146,147, Mari Nelis138, Igor Nenadic148, Deborah A. Nertney149, Gerald Nestadt150, Kristin K. Nicodemus151, Liene Nikitina-Zake112, Laura Nisenbaum152, Annelie Nordin153, Eadbhard O’Callaghan154, Colm O’Dushlaine6, F. Anthony O’Neill155, Sang-Yun Oh156, Ann Olincy83, Line Olsen21,93, Jim Van Os144,157, Christos Pantelis43,158, George N. Papadimitriou64, Sergi Papiol27, Elena Parkhomenko40, Michele T. Pato113, Tiina Paunio159,160, Milica Pejovic-Milovancevic161, Diana O. Perkins162, Olli Pietiläinen160,163, Jonathan Pimm57, Andrew J. Pocklington10, John Powell143, Alkes Price7,164, Ann E. Pulver150, Shaun M. Purcell86, Digby Quested165, Henrik B. Rasmussen21,93, Abraham Reichenberg40, Mark A. Reimers166, Alexander L. Richards10, Joshua L. Roffman34,36, Panos Roussos86,167, Douglas M. Ruderfer10,86, Veikko Salomaa75, Alan R. Sanders68,69, Ulrich Schall43,123, Christian R. Schubert168, Thomas G. Schulze81,169, Sibylle G. Schwab170, Edward M. Scolnick6, Rodney J. Scott43,171,172, Larry J. Seidman131,137, Jianxin Shi173, Engilbert Sigurdsson174, Teimuraz Silagadze175, Jeremy M. Silverman40,176, Kang Sim51, Petr Slominsky111, Jordan W. Smoller6,8, Hon-Cheong So47, Chris C. A. Spencer177, Eli A. Stahl7,86, Hreinn Stefansson178, Stacy Steinberg178, Elisabeth Stogmann179, Richard E. Straub180, Eric Strengman38,181, Jana Strohmaier81, T. Scott Stroup122, Mythily Subramaniam51, Jaana Suvisaari125, Dragan M. Svrakic52, Jin P. Szatkiewicz55, Erik Söderman16, Srinivas Thirumalai182, Draga Toncheva106, Sarah Tosato183, Juha Veijola184,185, John Waddington186, Dermot Walsh187, Dai Wang90, Qiang Wang120, Bradley T. Webb26, Mark Weiser58, Dieter B. Wildenauer188, Nigel M. Williams10, Stephanie Williams55, Stephanie H. Witt81, Aaron R. Wolen166, Emily H. M. Wong47, Brandon K. Wormley26, Hualin Simon Xi189, Clement C. Zai108,109, Xuebin Zheng190, Fritz Zimprich179, Kari Stefansson178, Peter M. 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