1. Age at first birth in women is genetically associated with increased risk of schizophrenia
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Fritz Zimprich, Manuel Mattheisen, Edward M. Scolnick, Ayman H. Fanous, Henrik B. Rasmussen, Steven A. McCarroll, Ingrid Agartz, Carmel M. Loughland, Aiden Corvin, Ann Olincy, Anders D. Børglum, F. Anthony O'Neill, T. Scott Stroup, Elizabeth Bevilacqua, Sandra Meier, Ulrich Schall, Jouko Lönnqvist, Jianxin Shi, C. Robert Cloninger, Judit Bene, Veikko Salomaa, George N. Papadimitriou, Milica Pejovic-Milovancevic, Béla Melegh, Kari Stefansson, Brendan Bulik-Sullivan, Janis Klovins, Enrico Domenici, Sibylle G. Schwab, Dai Wang, Assen Jablensky, Mari Nelis, Sang Yun Oh, Peter Holmans, Aaron R. Wolen, Hualin Simon Xi, Eric Strengman, Bryan J. Mowry, Michael Gill, Kung Yee Liang, William Byerley, Rolf Adolfsson, Hugh Gurling, Joseph I. Friedman, Andrew Pocklington, Brien P. Riley, Engilbert Sigurdsson, Benjamin M. Neale, Miaoxin Li, Michael Davidson, Bernard Lerer, Michele T. Pato, Xuebin Zheng, Patrick F. Sullivan, Frans Henskens, Madeline Alexander, Andrew M. McIntosh, Inez Myin-Germeys, Draga Toncheva, Liene Nikitina-Zake, Kenneth S. Kendler, Carin J. Meijer, Robin M. Murray, Richard E. Straub, Ann E. Pulver, Menachem Fromer, Derek W. Morris, Douglas M. Ruderfer, Mythily Subramaniam, Paul Cormican, Lyudmila Georgieva, Giulio Genovese, Brion S. Maher, Stanley V. Catts, David St Clair, Robert W. McCarley, David Cohen, Nancy G. Buccola, Dan Rujescu, Carlos N. Pato, Kristin K. Nicodemus, Josef Frank, Claudine Laurent, Dominique Campion, Guiyan Ni, James L. Kennedy, Sena Karachanak-Yankova, Nicholas John Craddock, Peter M. Visscher, Valentina Escott-Price, Jeffrey A. Lieberman, Deborah A. Nertney, Bertram Müller-Myhsok, Marcella Rietschel, Dimitris Dikeos, Stephanie Godard, Stephanie Williams, Andres Metspalu, John L. Waddington, Sophie E. Legge, Roel A. Ophoff, Jonathan Pimm, Richard Bruggeman, Tim B. Bigdeli, Gerald Nestadt, Mark Weiser, Kieran C. Murphy, Eric F.C. Cheung, Kang Sim, Jordan W. Smoller, David J. Kavanagh, Inge Joa, Jens R. Wendland, Thomas G. Schulze, Richard A. Belliveau, Sarah E. Bergen, Ditte Demontis, David Curtis, Todd Lencz, Danielle Posthuma, René S. Kahn, Lili Milani, Randy L. Buckner, Jianjun Liu, Petr Slominsky, Wiepke Cahn, Hana Kuzelova-Ptackova, Sergi Papiol, Tune H. Pers, Stephan Ripke, Rita M. Cantor, Ariel Darvasi, Christina M. Hultman, Larry J. Seidman, Eli A. Stahl, David A. Collier, Michael Conlon O'Donovan, Svetlana A. Limborska, James T.R. Walters, Farooq Amin, Noa Carrera, Ronald Y.L. Chen, Pablo V. Gejman, Joel N. Hirschhorn, Zita Ausrele Kucinskiene, Michael John Owen, Ina Giegling, Stephanie H. Witt, Timothy G. Dinan, Margot Albus, Wei Cheng, Marian L. Hamshere, Markus M. Nöthen, Thomas Werge, Guiqing Cai, Raquelle I. Mesholam-Gately, Annette M. Hartmann, Ingrid Melle, Ole A. Andreassen, Preben Bo Mortensen, Hannelore Ehrenreich, Tiina Paunio, James A. Knowles, Pak C. Sham, Marion Friedl, Teimuraz Silagadze, Dermot Walsh, Emily H. M. Wong, Igor Nenadic, Matthew C. Keller, John Powell, Naomi R. Wray, Patricia T. Michie, Bradley T. Webb, Lude Franke, Mark Hansen, Masashi Ikeda, Sven Cichon, Elvira Bramon, Frank Dudbridge, Erik G. Jönsson, Annelie Nordin, Wolfgang Maier, Peter Eichhammer, Christian R. Schubert, J. Mallet, Jacob Gratten, Andrey Khrunin, Jacqueline I. Goldstein, Panos Roussos, Pamela Sklar, Diana O. Perkins, Srdjan Djurovic, Phil Lee, Elodie Drapeau, Douglas F. Levinson, Nadine Cohen, Luba Kalaydjieva, Brandon Wormley, Tao Li, Tõnu Esko, Alexander Richards, Srihari Gopal, Jubao Duan, Anil K. Malhotra, Elisabeth Stögmann, Gary Donohoe, Kimberly Chambert, Sara Marsal, Hreinn Stefansson, Jo Knight, Ole Mors, Per Hoffmann, Dieter B. Wildenauer, James J. Crowley, Srinivas Thirumalai, Vahram Haroutunian, A. Hofman, Hailiang Huang, Thomas Hansen, Daniel R. Weinberger, Andrew McQuillin, Vaughan J. Carr, Vaidutis Kučinskas, Jimmy Lee Chee Keong, Digby Quested, Aarno Palotie, Robert Freedman, Hon-Cheong So, Jennifer L. Moran, Donald W. Black, Mark Reimers, Abraham Reichenberg, Jurgen Del Favero, Paola Giusti-Rodríguez, Tracey L. Petryshen, Olli Pietiläinen, Franziska Degenhardt, Laurent Essioux, Esben Agerbo, Qiang Wang, Jana Strohmaier, Siow Ann Chong, Johan G. Eriksson, Martin Begemann, Younes Mokrab, Colm McDonald, Silviu Alin Bacanu, Martilias S. Farrell, Christos Pantelis, Kai How Farh, Line Olsen, Naser Durmishi, Antonio Julià, Stefan Herms, Qingqin S. Li, Bettina Konte, George Kirov, Rodney J. Scott, Nelson B. Freimer, Mads V. Hollegaard, Shaun Purcell, Erik Söderman, Dragan M. Svrakic, Patrik K. E. Magnusson, Douglas Blackwood, Jin P. Szatkiewicz, Sang Hong Lee, Yunjung Kim, Colm O'Dushlaine, Morten Mattingsdal, Jim van Os, Sarah Tosato, Milan Macek, Joshua L. Roffman, Jan Lubinski, Eadbhard O'Callaghan, Juha Karjalainen, Vera Golimbet, Anna K. Kähler, Clement C. Zai, Nigel Williams, Joseph D. Buxbaum, Laura Nisenbaum, Eric Y.H. Chen, David M. Hougaard, Jaana Suvisaari, Chris C. A. Spencer, Alan R. Sanders, Alkes L. Price, Vihra Milanova, Juha Veijola, Christian Hammer, Raymond C.K. Chan, Stacy Steinberg, Nakao Iwata, Jeremy M. Silverman, Mark J. Daly, Elena Parkhomenko, Kenneth L. Davis, Lieuwe de Haan, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Kučinskas, Vaidutis, Kučinskienė, Zita Aušrelė, Ni, Guiyan, Gratten, Jacob, Wray, Naomi R, Lee, Sang Hong, Germeys, Inez, Complex Trait Genetics, Háskóli Íslands, University of Iceland, Child and Adolescent Psychiatry / Psychology, Research Programs Unit, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, University Management, Department of Psychiatry, Center for Population, Health and Society, Department of Public Health, Centre of Excellence in Complex Disease Genetics, Research Programme of Molecular Medicine, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, and Genomics of Neurological and Neuropsychiatric Disorders
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0301 basic medicine ,Multifactorial Inheritance ,PATERNAL-AGE ,3124 Neurology and psychiatry ,COMMON SNPS ,fluids and secretions ,0302 clinical medicine ,CHILD ,Risk Factors ,Pregnancy ,2.1 Biological and endogenous factors ,Medicine ,Aetiology ,Pediatric ,PROPORTION ,Schizophrenia Working Group of the Psychiatric Genomics Consortium ,0303 health sciences ,Multidisciplinary ,PSYCHIATRIC-DISORDERS ,BIPOLAR DISORDER ,Biobank ,3. Good health ,AFB ,Mental Health ,Schizophrenia ,Female ,Erfðarannsóknir ,Psychosocial ,TRAITS ,schizophrenia, age at birth, AFB ,Maternal Age ,Adult ,age at first birth in women ,genetic association ,Offspring ,Science ,Genetic correlation ,Article ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Geðklofi ,Genetics ,age at birth ,Humans ,Genetic Predisposition to Disease ,Bipolar disorder ,General ,Biology ,Genetic association study ,030304 developmental biology ,Genetic association ,business.industry ,Genetic heterogeneity ,Prevention ,average aged parents ,Parturition ,SCORE REGRESSION ,bacterial infections and mycoses ,medicine.disease ,Mental health ,Brain Disorders ,respiratory tract diseases ,schizophrenia ,Good Health and Well Being ,030104 developmental biology ,younger and older parents ,DE-NOVO MUTATIONS ,ddc:000 ,Human medicine ,business ,030217 neurology & neurosurgery ,Demography - Abstract
Publisher's version (útgefin grein), 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., This research is supported by the Australian National Health and Medical Research Council (1080157, 1087889, 1103418, 1127440), and the Australian Research Council (DP160102126, FT160100229). This research has been conducted using the UK Biobank Resource. UK Biobank (http://www.ukbiobank.ac.uk) Research Ethics Committee (REC) approval number is 11/NW/0382. Our reference number approved by UK Biobank is 14575.
- Published
- 2017