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

Stephan Ripke,Benjamin M. Neale,Aiden Corvin,James T. R. Walters, Kai-How, Farh,Peter A. Holmans,Phil Lee,Brendan Bulik-Sullivan,David A. Collier,Hailiang Huang,Tune H. Pers,Ingrid Agartz,Esben Agerbo, Margot, Albus,Madeline Alexander,Farooq Amin,Silviu A. Bacanu,Martin Begemann,Richard A. Belliveau,Judit Bene,Sarah E. Bergen, Elizabeth Bevilacqua,B. Tim, Bigdeli,Donald W. Black,Richard Bruggeman,Nancy G. Buccola, L. Randy, Buckner,William Byerley,Wiepke Cahn,Guiqing Cai,Dominique Campion,Rita M. Cantor,Vaughan J. Carr,Noa Carrera,Stanley V. Catts, D. Kimberly, Chambert, Raymond C. K. Chan,Ronald Y. L. Chen,Eric Y. H. Chen,Wei Cheng,Eric F. C. Cheung,Siow Ann Chong,C. Robert Cloninger,David Cohen,Nadine Cohen,Paul Cormican,Nick Craddock,James J. Crowley,David Curtis,Michael Davidson,Kenneth L. Davis,Franziska Degenhardt,Jurgen Del Favero,Ditte Demontis,Dimitris Dikeos,Timothy Dinan,Srdjan Djurovic,Gary Donohoe,Elodie Drapeau,Jubao Duan,Frank Dudbridge,Naser Durmishi,Peter Eichhammer, Johan, Eriksson,Valentina Escott-Price,Laurent Essioux,Ayman H. Fanous,Martilias S. Farrell,Josef Frank,Lude Franke,Robert Freedman,Marion Friedl,Joseph I. Friedman,Menachem Fromer,Giulio Genovese, Lyudmila, Georgieva,Ina Giegling,Paola Giusti-Rodríguez,Stephanie Godard, I. Jacqueline, Goldstein,Vera Golimbet,Srihari Gopal,Lieuwe de Haan,Christian Hammer,Marian, L. Hamshere,Mark Hansen,Thomas Hansen,Vahram Haroutunian, M. Annette, Hartmann,Frans A. Henskens,Stefan Herms,Joel N. Hirschhorn, Per, Hoffmann,Andrea Hofman,Mads V. Hollegaard,David M. Hougaard, Masashi, Ikeda,Inge Joa,Antonio Juliá,René S. Kahn,Luba Kalaydjieva, Sena, Karachanak-Yankova,Juha Karjalainen,David Kavanagh,Matthew C. Keller,L. James, Kennedy,Andrey Khrunin,Yunjung Kim,Janis Klovins,James A. Knowles,Bettina Konte,Vaidutis Kucinskas, - HanaKuzelova, Ptackova,Anna K. Kähler,Claudine Laurent,Jimmy Lee Chee Keong, E. Sophie,Bernard Lerer,Miaoxin Li,Tao Li,Kung-Yee Liang, Jeffrey, Lieberman,Svetlana Limborska,Carmel M. Loughland,Jan Lubinski, Jouko, Lönnqvist,Milan Macek,Patrik K. E. Magnusson,Brion S. Maher,Wolfgang Maier,Jacques Mallet,Sara Marsal,Manuel Mattheisen,Morten Mattingsdal,Robert W. McCarley,Colm McDonald,Andrew M. McIntosh,Sandra Meier,Carin J. Meijer,Bela Melegh,Ingrid Melle,Raquelle I. Mesholam-Gately,Andres Metspalu,Patricia T. Michie,Lili Milani,Vihra Milanova,Younes Mokrab,Derek W. Morris,Ole Mors,Kieran C. Murphy,Robin M. Murray,Mari Nelis,Igor Nenadic, A. Deborah, Nertney,Gerald Nestadt, Annelie Nordin,Eadbhard O’Callaghan,Colm O’Dushlaine, F. Anthony, O’Neill,Sang-Yun Oh,Line Olsen,Jim Van Os, Christos, Pantelis,George N. Papadimitriou,Sergi Papiol, Elena Parkhomenko, T. Michele, Pato,Diana O. Perkins, Olli, Pietiläinen,Jonathan Pimm,Andrew J. Pocklington,John Powell,Alkes Price,Ann E. Pulver,Shaun M. Purcell,Digby Quested,Henrik B. Rasmussen, Abraham, Reichenberg,Mark A. Reimers,Alexander L. Richards,Joshua L. Roffman, Panos, Roussos,Douglas M. Ruderfer,Veikko Salomaa,Alan R. Sanders, Ulrich, Schall,Sibylle G. Schwab, M. Edward, Scolnick,Rodney J. Scott, Engilbert, Sigurdsson, Teimuraz Silagadze,Jeremy M. Silverman, Petr, Slominsky,Jordan W. Smoller,Chris C. A. Spencer,Eli A. Stahl,Hreinn Stefansson,Stacy Steinberg,Elisabeth Stogmann,Richard E. Straub, Eric, Strengman,Jana Strohmaier,T. Scott Stroup,Mythily Subramaniam, Jaana, Suvisaari,Dragan M. Svrakic,Jin P. Szatkiewicz,Erik Söderman, Srinivas, Thirumalai,Draga Toncheva,Sarah Tosato,Juha Veijola,John Waddington,Dermot Walsh,Qiang Wang,Bradley T. Webb,Mark Weiser,Dieter B. Wildenauer,Nigel M. Williams, Stephanie Williams,Stephanie H. Witt

semanticscholar(2018)

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摘要
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.
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