Age at first birth in women is genetically associated with increased risk of schizophrenia
Authors: Ni Guiyan , Gratten Jacob , Wray Naomi R. , Lee Sang Hong ,   Schizophrenia Working Group of the Psychiatric Genomics Consortium, Ripke Stephan , Neale Benjamin M. , Corvin Aiden , Walters James T. R. , Farh Kai-How , Holmans Peter A. , Lee Phil , Bulik-Sullivan Brendan , Collier David A. , Huang Hailiang , Pers Tune H. , Agartz Ingrid , Agerbo Esben , Albus Margot , Alexander Madeline , Amin Farooq , Bacanu Silviu A. , Begemann Martin , Belliveau Richard A. , Bene Judit , Bergen Sarah E. , Bevilacqua Elizabeth , Bigdeli Tim B. , Black Donald W. , Bruggeman Richard , Buccola Nancy G. , Buckner Randy L. , Byerley William , Cahn Wiepke , Cai Guiqing , Campion Dominique , Cantor Rita M. , Carr Vaughan J. , Carrera Noa , Catts Stanley V. , Chambert Kimberly D. , Chan Raymond C. K. , Chen Ronald Y. L. , Chen Eric Y. H. , Cheng Wei , Cheung Eric F. C. , Chong Siow Ann , Cloninger C. Robert , Cohen David , Cohen Nadine , Cormican Paul , Craddock Nick , Crowley James J. , Curtis David , Davidson Michael , Davis Kenneth L. , Degenhardt Franziska , Del Favero Jurgen , Demontis Ditte , Dikeos Dimitris , Dinan Timothy , Djurovic Srdjan , Donohoe Gary , Drapeau Elodie , Duan Jubao , Dudbridge Frank , Durmishi Naser , Eichhammer Peter , Eriksson Johan , Escott-Price Valentina , Essioux Laurent , Fanous Ayman H. , Farrell Martilias S. , Frank Josef , Franke Lude , Freedman Robert , Freimer Nelson B. , Friedl Marion , Friedman Joseph I. , Fromer Menachem , Genovese Giulio , Georgieva Lyudmila , Giegling Ina , Giusti-Rodríguez Paola , Godard Stephanie , Goldstein Jacqueline I. , Golimbet Vera , Gopal Srihari , Haan Lieuwe de , Hammer Christian , Hamshere Marian L. , Hansen Mark , Hansen Thomas , Haroutunian Vahram , Hartmann Annette M. , Henskens Frans A. , Herms Stefan , Hirschhorn Joel N. , Hoffmann Per , Hofman Andrea , Hollegaard Mads V. , Hougaard David M. , Ikeda Masashi , Joa Inge , Juliá Antonio , Kahn René S. , Kalaydjieva Luba , Karachanak-Yankova Sena , Karjalainen Juha , Kavanagh David , Keller Matthew C. , Kennedy James L. , Khrunin Andrey , Kim Yunjung , Klovins Janis , Knowles James A. , Konte Bettina , Kucinskas Vaidutis , Kucinskiene Zita Ausrele , Kuzelova-Ptackova Hana , Kähler Anna K. , Laurent Claudine , Keong Jimmy Lee Chee , Legge Sophie E. , Lerer Bernard , Li Miaoxin , Li Tao , Liang Kung-Yee , Lieberman Jeffrey , Limborska Svetlana , Loughland Carmel M. , Lubinski Jan , Lönnqvist Jouko , Macek Milan , Magnusson Patrik K. E. , Maher Brion S. , Maier Wolfgang , Mallet Jacques , Marsal Sara , Mattheisen Manuel , Mattingsdal Morten , McCarley Robert W. , McDonald Colm , McIntosh Andrew M. , Meier Sandra , Meijer Carin J. , Melegh Bela , Melle Ingrid , Mesholam-Gately Raquelle I. , Metspalu Andres , Michie Patricia T. , Milani Lili , Milanova Vihra , Mokrab Younes , Morris Derek W. , Mors Ole , Murphy Kieran C. , Murray Robin M. , Myin-Germeys Inez , Müller-Myhsok Bertram , Nelis Mari , Nenadic Igor , Nertney Deborah A. , Nestadt Gerald , Nicodemus Kristin K. , Nikitina-Zake Liene , Nisenbaum Laura , Nordin Annelie , O’Callaghan Eadbhard , O’Dushlaine Colm , O’Neill F. Anthony , Oh Sang-Yun , Olincy Ann , Olsen Line , Os Jim Van , Pantelis Christos , Papadimitriou George N. , Papiol Sergi , Parkhomenko Elena , Pato Michele T. , Paunio Tiina , Pejovic-Milovancevic Milica , Perkins Diana O. , Pietiläinen Olli , Pimm Jonathan , Pocklington Andrew J. , Powell John , Price Alkes , Pulver Ann E. , Purcell Shaun M. , Quested Digby , Rasmussen Henrik B. , Reichenberg Abraham , Reimers Mark A. , Richards Alexander L. , Roffman Joshua L. , Roussos Panos , Ruderfer Douglas M. , Salomaa Veikko , Sanders Alan R. , Schall Ulrich , Schubert Christian R. , Schulze Thomas G. , Schwab Sibylle G. , Scolnick Edward M. , Scott Rodney J. , Seidman Larry J. , Shi Jianxin , Sigurdsson Engilbert , Silagadze Teimuraz , Silverman Jeremy M. , Sim Kang , Slominsky Petr , Smoller Jordan W. , So Hon-Cheong , Spencer Chris C. A. , Stahl Eli A. , Stefansson Hreinn , Steinberg Stacy , Stogmann Elisabeth , Straub Richard E. , Strengman Eric , Strohmaier Jana , Stroup T. Scott , Subramaniam Mythily , Suvisaari Jaana , Svrakic Dragan M. , Szatkiewicz Jin P. , Söderman Erik , Thirumalai Srinivas , Toncheva Draga , Tosato Sarah , Veijola Juha , Waddington John , Walsh Dermot , Wang Dai , Wang Qiang , Webb Bradley T. , Weiser Mark , Wildenauer Dieter B. , Williams Nigel M. , Williams Stephanie , Witt Stephanie H. , Wolen Aaron R. , Wong Emily H. M. , Wormley Brandon K. , Xi Hualin Simon , Zai Clement C. , Zheng Xuebin , Zimprich Fritz , Stefansson Kari , Visscher Peter M. , Adolfsson Rolf , Andreassen Ole A. , Blackwood Douglas H. R. , Bramon Elvira , Buxbaum Joseph D. , Børglum Anders D. , Cichon Sven , Darvasi Ariel , Domenici Enrico , Ehrenreich Hannelore , Esko Tõnu , Gejman Pablo V. , Gill Michael , Gurling Hugh , Hultman Christina M. , Iwata Nakao , Jablensky Assen V. , Jönsson Erik G. , Kendler Kenneth S. , Kirov George , Knight Jo , Lencz Todd , Levinson Douglas F. , Li Qingqin S. , Liu Jianjun , Malhotra Anil K. , McCarroll Steven A. , McQuillin Andrew , Moran Jennifer L. , Mortensen Preben B. , Mowry Bryan J. , Nöthen Markus M. , Ophoff Roel A. , Owen Michael J. , Palotie Aarno , Pato Carlos N. , Petryshen Tracey L. , Posthuma Danielle , Rietschel Marcella , Riley Brien P. , Rujescu Dan , Sham Pak C. , Sklar Pamela , Clair David St. , Weinberger Daniel R. , Wendland Jens R. , Werge Thomas , Daly Mark J. , Sullivan Patrick F. , O’Donovan Michael C. 
Published: June 2018

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.