Age at first birth in women is genetically associated with increased risk of schizophrenia
Guiyan Ni,Guiyan Ni,Jacob Gratten,Naomi R. Wray,Sang Hong Lee,Sang Hong Lee,Sang Hong Lee,Stephan Ripke,Stephan Ripke,Benjamin M. Neale,Benjamin M. Neale,Aiden Corvin,James T.R. Walters,Kai How Farh,Peter Holmans,Phil Lee,Phil Lee,Brendan Bulik-Sullivan,Brendan Bulik-Sullivan,David A. Collier,David A. Collier,Hailiang Huang,Hailiang Huang,Tune H. Pers,Tune H. Pers,Tune H. Pers,Ingrid Agartz,Ingrid Agartz,Esben Agerbo,Esben Agerbo,Margot Albus,Madeline Alexander,Farooq Amin,Farooq Amin,Silviu Alin Bacanu,Martin Begemann,Richard A. Belliveau,Judit Bene,Sarah E. Bergen,Sarah E. Bergen,Elizabeth Bevilacqua,Tim B. Bigdeli,Donald W. Black,Richard Bruggeman,Nancy G. Buccola,Randy L. Buckner,William Byerley,Wiepke Cahn,Guiqing Cai,Dominique Campion,Rita M. Cantor,Vaughan J. Carr,Noa Carrera,Stanley V. Catts,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,Nicholas John Craddock,James J. Crowley,David Curtis,David Curtis,Michael Davidson,Kenneth L. Davis,Franziska Degenhardt,Jurgen Del Favero,Ditte Demontis,Ditte Demontis,Dimitris Dikeos,Timothy G. Dinan,Srdjan Djurovic,Gary Donohoe,Gary Donohoe,Elodie Drapeau,Jubao Duan,Jubao Duan,Frank Dudbridge,Naser Durmishi,Peter Eichhammer,Johan G. Eriksson,Johan G. Eriksson,Valentina Escott-Price,Laurent Essioux,Ayman H. Fanous,Martilias S. Farrell,Josef Frank,Lude Franke,Robert Freedman,Nelson B. Freimer,Marion Friedl,Joseph I. Friedman,Menachem Fromer,Menachem Fromer,Menachem Fromer,Giulio Genovese,Lyudmila Georgieva,Ina Giegling,Ina Giegling,Paola Giusti-Rodríguez,Stephanie Godard,Jacqueline I. Goldstein,Jacqueline I. Goldstein,Vera Golimbet,Srihari Gopal,Lieuwe de Haan,Christian Hammer,Marian L. Hamshere,Mark Hansen,Thomas Hansen,Vahram Haroutunian,Vahram Haroutunian,Annette M. Hartmann,Frans Henskens,Stefan Herms,Stefan Herms,Joel N. Hirschhorn,Joel N. Hirschhorn,Per Hoffmann,Per Hoffmann,A. Hofman,Mads V. Hollegaard,David M. Hougaard,Masashi Ikeda,Inge Joa,Antonio Julià,René S. Kahn,Luba Kalaydjieva,Sena Karachanak-Yankova,Juha Karjalainen,David J. Kavanagh,Matthew C. Keller,James L. Kennedy,Andrey Khrunin,Yunjung Kim,Janis Klovins,James A. Knowles,Bettina Konte,Vaidutis Kučinskas,Zita Ausrele Kucinskiene,Hana Kuzelova-Ptackova,Anna K. Kähler,Claudine Laurent,Claudine Laurent,Jimmy Lee Chee Keong,Sophie E. Legge,Bernard Lerer,Miaoxin Li,Tao Li,Kung Yee Liang,Jeffrey A. Lieberman,Svetlana A. Limborska,Carmel M. Loughland,Jan Lubinski,Jouko Lönnqvist,Milan Macek,Patrik K. E. Magnusson,Brion S. Maher,Wolfgang Maier,J. Mallet,Sara Marsal,Manuel Mattheisen,Manuel Mattheisen,Manuel Mattheisen,Morten Mattingsdal,Robert W. McCarley,Colm McDonald,Andrew M. McIntosh,Sandra Meier,Carin J. Meijer,Béla Melegh,Ingrid Melle,Raquelle I. Mesholam-Gately,Andres Metspalu,Patricia T. Michie,Lili Milani,Vihra Milanova,Younes Mokrab,Derek W. Morris,Derek W. Morris,Ole Mors,Ole Mors,Kieran C. Murphy,Robin M. Murray,Inez Myin-Germeys,Bertram Müller-Myhsok,Bertram Müller-Myhsok,Mari Nelis,Igor Nenadic,Deborah A. Nertney,Gerald Nestadt,Kristin K. Nicodemus,Liene Nikitina-Zake,Laura Nisenbaum,Annelie Nordin,Eadbhard O'Callaghan,Colm O'Dushlaine,F. Anthony O'Neill,Sang Yun Oh,Ann Olincy,Line Olsen,Jim van Os,Jim van Os,Christos Pantelis,George N. Papadimitriou,Sergi Papiol,Elena Parkhomenko,Michele T. Pato,Tiina Paunio,Tiina Paunio,Milica Pejovic-Milovancevic,Diana O. Perkins,Olli Pietiläinen,Olli Pietiläinen,Jonathan Pimm,Andrew Pocklington,John Powell,Alkes L. Price,Alkes L. Price,Ann E. Pulver,Shaun Purcell,Digby Quested,Henrik B. Rasmussen,Abraham Reichenberg,Mark Reimers,Alexander Richards,Joshua L. Roffman,Panos Roussos,Douglas M. Ruderfer,Douglas M. Ruderfer,Veikko Salomaa,Alan R. Sanders,Alan R. Sanders,Ulrich Schall,Christian R. Schubert,Thomas G. Schulze,Thomas G. Schulze,Sibylle G. Schwab,Edward M. Scolnick,Rodney J. Scott,Larry J. Seidman,Jianxin Shi,Engilbert Sigurdsson,Teimuraz Silagadze,Jeremy M. Silverman,Jeremy M. Silverman,Kang Sim,Petr Slominsky,Jordan W. Smoller,Jordan W. Smoller,Hon-Cheong So,Chris C. A. Spencer,Eli A. Stahl,Eli A. Stahl,Hreinn Stefansson,Stacy Steinberg,Elisabeth Stögmann,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 L. Waddington,Dermot Walsh,Dai Wang,Qiang Wang,Bradley T. Webb,Mark Weiser,Dieter B. Wildenauer,Nigel Williams,Stephanie Williams,Stephanie H. Witt,Aaron R. Wolen,Emily H. M. Wong,Brandon Wormley,Hualin Simon Xi,Clement C. Zai,Xuebin Zheng,Fritz Zimprich,Kari Stefansson,Peter M. Visscher,Rolf Adolfsson,Ole A. Andreassen,Douglas Blackwood,Elvira Bramon,Joseph D. Buxbaum,Anders D. Børglum,Anders D. Børglum,Sven Cichon,Sven Cichon,Ariel Darvasi,Enrico Domenici,Hannelore Ehrenreich,Tõnu Esko,Tõnu Esko,Tõnu Esko,Pablo V. Gejman,Pablo V. Gejman,Michael Gill,Hugh Gurling,Christina M. Hultman,Nakao Iwata,Assen Jablensky,Erik G. Jönsson,Erik G. Jönsson,Kenneth S. Kendler,George Kirov,Jo Knight,Todd Lencz,Todd Lencz,Douglas F. Levinson,Qingqin S. Li,Jianjun Liu,Jianjun Liu,Anil K. Malhotra,Anil K. Malhotra,Steven A. McCarroll,Steven A. McCarroll,Andrew McQuillin,Jennifer L. Moran,Preben Bo Mortensen,Preben Bo Mortensen,Bryan J. Mowry,Bryan J. Mowry,Markus M. Nöthen,Roel A. Ophoff,Roel A. Ophoff,Michael John Owen,Aarno Palotie,Aarno Palotie,Aarno Palotie,Carlos N. Pato,Tracey L. Petryshen,Tracey L. Petryshen,Danielle Posthuma,Danielle Posthuma,Marcella Rietschel,Brien P. Riley,Dan Rujescu,Dan Rujescu,Pak C. Sham,Pamela Sklar,David St Clair,Daniel R. Weinberger,Jens R. Wendland,Thomas Werge,Thomas Werge,Mark J. Daly,Mark J. Daly,Patrick F. Sullivan,Patrick F. Sullivan,Michael Conlon O'Donovan +365 more
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The 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, contributing new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.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.read more
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Significant shared heritability underlies suicide attempt and clinically predicted probability of attempting suicide
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TL;DR: The findings suggest that the risk of ASD associated with young or advanced grandparental age might be transmitted across generations, which should be considered in future research of the causes of ASD.
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Associations of parental age with offspring all-cause and cause-specific adult mortality.
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Murray,Inez Myin-Germeys,Bertram Mueller-Myhsok,Mari Nelis,Igor Nenadic,Deborah A. Nertney,Gerald Nestadt,Kristin K. Nicodemus,Liene Nikitina-Zake,Laura Nisenbaum,Annelie Nordin,Eadbhard O'Callaghan,Colm O'Dushlaine,F. Anthony O'Neill,Sang-Yun Oh,Ann Olincy,Line Olsen,Jim van Os,Jim van Os,Christos Pantelis,George N. Papadimitriou,Sergi Papiol,Elena Parkhomenko,Michele T. Pato,Tiina Paunio,Tiina Paunio,Milica Pejovic-Milovancevic,Diana O. Perkins,Olli Pietiläinen,Olli Pietiläinen,Jonathan Pimm,Andrew Pocklington,John Powell,Alkes L. Price,Alkes L. Price,Ann E. Pulver,Shaun Purcell,Digby Quested,Henrik B. Rasmussen,Abraham Reichenberg,Mark Reimers,Alexander Richards,Joshua L. Roffman,Panos Roussos,Douglas M. Ruderfer,Douglas M. Ruderfer,Veikko Salomaa,Alan R. Sanders,Ulrich Schall,Christian R. Schubert,Thomas G. Schulze,Thomas G. Schulze,Sibylle G. Schwab,Edward M. Scolnick,Rodney J. Scott,Larry J. Seidman,Jianxin Shi,Engilbert Sigurdsson,Teimuraz Silagadze,Jeremy M. Silverman,Jeremy M. Silverman,Kang Sim,Petr Slominsky,Jordan W. Smoller,Jordan W. Smoller,Hon-Cheong So,Chris C. A. Spencer,Eli A. Stahl,Eli A. Stahl,Hreinn Stefansson,Stacy Steinberg,Elisabeth Stögmann,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 L. Waddington,Dermot Walsh,Dai Wang,Qiang Wang,Bradley T. Webb,Mark Weiser,Dieter B. Wildenauer,Nigel Williams,Stephanie Williams,Stephanie H. Witt,Aaron R. Wolen,Emily H. M. Wong,Brandon Wormley,Hualin Simon Xi,Clement C. Zai,Xuebin Zheng,Fritz Zimprich,Naomi R. Wray,Kari Stefansson,Peter M. Visscher,Rolf Adolfsson,Ole A. Andreassen,Douglas Blackwood,Elvira Bramon,Joseph D. Buxbaum,Anders D. Børglum,Anders D. Børglum,Sven Cichon,Sven Cichon,Ariel Darvasi,Enrico Domenici,Hannelore Ehrenreich,Tõnu Esko,Tõnu Esko,Tõnu Esko,Pablo V. Gejman,Michael Gill,Hugh Gurling,Christina M. Hultman,Nakao Iwata,Assen Jablensky,Erik G. Jönsson,Erik G. Jönsson,Kenneth S. Kendler,George Kirov,Jo Knight,Todd Lencz,Todd Lencz,Douglas F. Levinson,Qingqin S. Li,Jianjun Liu,Jianjun Liu,Anil K. Malhotra,Anil K. Malhotra,Steven A. McCarroll,Steven A. McCarroll,Andrew McQuillin,Jennifer L. Moran,Preben Bo Mortensen,Preben Bo Mortensen,Bryan J. Mowry,Markus M. Noethen,Roel A. Ophoff,Roel A. Ophoff,Michael John Owen,Aarno Palotie,Aarno Palotie,Aarno Palotie,Carlos N. Pato,Tracey L. Petryshen,Tracey L. Petryshen,Danielle Posthuma,Danielle Posthuma,Marcella Rietschel,Brien P. Riley,Dan Rujescu,Dan Rujescu,Pak C. Sham,Pamela Sklar,David St Clair,Daniel R. Weinberger,Jens R. Wendland,Thomas Werge,Thomas Werge,Mark J. Daly,Mark J. Daly,Patrick F. Sullivan,Patrick F. Sullivan,Michael Conlon O'Donovan +354 more
TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
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