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.
| Original language | English |
|---|---|
| Article number | 10168 |
| Journal | Scientific Reports |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2018 |
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In: Scientific Reports, Vol. 8, No. 1, 10168, 01.12.2018.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Age at first birth in women is genetically associated with increased risk of schizophrenia
AU - Ni, Guiyan
AU - Gratten, Jacob
AU - Wray, Naomi R.
AU - Lee, Sang Hong
AU - Ripke, Stephan
AU - Neale, Benjamin M.
AU - Corvin, Aiden
AU - Walters, James T.R.
AU - Farh, Kai How
AU - Holmans, Peter A.
AU - Lee, Phil
AU - Bulik-Sullivan, Brendan
AU - Collier, David A.
AU - Huang, Hailiang
AU - Pers, Tune H.
AU - Agartz, Ingrid
AU - Agerbo, Esben
AU - Albus, Margot
AU - Alexander, Madeline
AU - Amin, Farooq
AU - Bacanu, Silviu A.
AU - Begemann, Martin
AU - Belliveau, Richard A.
AU - Bene, Judit
AU - Bergen, Sarah E.
AU - Bevilacqua, Elizabeth
AU - Bigdeli, Tim B.
AU - Black, Donald W.
AU - Bruggeman, Richard
AU - Buccola, Nancy G.
AU - Buckner, Randy L.
AU - Byerley, William
AU - Cahn, Wiepke
AU - Cai, Guiqing
AU - Campion, Dominique
AU - Cantor, Rita M.
AU - Carr, Vaughan J.
AU - Carrera, Noa
AU - Catts, Stanley V.
AU - Chambert, Kimberly D.
AU - Chan, Raymond C.K.
AU - Chen, Ronald Y.L.
AU - Chen, Eric Y.H.
AU - Cheng, Wei
AU - Cheung, Eric F.C.
AU - Chong, Siow Ann
AU - Cloninger, C. Robert
AU - Cohen, David
AU - Cohen, Nadine
AU - Cormican, Paul
AU - Craddock, Nick
AU - Crowley, James J.
AU - Curtis, David
AU - Davidson, Michael
AU - Davis, Kenneth L.
AU - Degenhardt, Franziska
AU - Del Favero, Jurgen
AU - Demontis, Ditte
AU - Dikeos, Dimitris
AU - Dinan, Timothy
AU - Djurovic, Srdjan
AU - Donohoe, Gary
AU - Drapeau, Elodie
AU - Duan, Jubao
AU - Dudbridge, Frank
AU - Durmishi, Naser
AU - Eichhammer, Peter
AU - Eriksson, Johan
AU - Escott-Price, Valentina
AU - Essioux, Laurent
AU - Fanous, Ayman H.
AU - Farrell, Martilias S.
AU - Frank, Josef
AU - Franke, Lude
AU - Freedman, Robert
AU - Freimer, Nelson B.
AU - Friedl, Marion
AU - Friedman, Joseph I.
AU - Fromer, Menachem
AU - Genovese, Giulio
AU - Georgieva, Lyudmila
AU - Giegling, Ina
AU - Giusti-Rodríguez, Paola
AU - Godard, Stephanie
AU - Goldstein, Jacqueline I.
AU - Golimbet, Vera
AU - Gopal, Srihari
AU - Haan, Lieuwe De
AU - Hammer, Christian
AU - Hamshere, Marian L.
AU - Hansen, Mark
AU - Hansen, Thomas
AU - Haroutunian, Vahram
AU - Hartmann, Annette M.
AU - Henskens, Frans A.
AU - Herms, Stefan
AU - Hirschhorn, Joel N.
AU - Hoffmann, Per
AU - Hofman, Andrea
AU - Hollegaard, Mads V.
AU - Hougaard, David M.
AU - Ikeda, Masashi
AU - Joa, Inge
AU - Juliá, Antonio
AU - Kahn, René S.
AU - Kalaydjieva, Luba
AU - Karachanak-Yankova, Sena
AU - Karjalainen, Juha
AU - Kavanagh, David
AU - Keller, Matthew C.
AU - Kennedy, James L.
AU - Khrunin, Andrey
AU - Kim, Yunjung
AU - Klovins, Janis
AU - Knowles, James A.
AU - Konte, Bettina
AU - Kucinskas, Vaidutis
AU - Kucinskiene, Zita Ausrele
AU - Kuzelova-Ptackova, Hana
AU - Kähler, Anna K.
AU - Laurent, Claudine
AU - Keong, Jimmy Lee Chee
AU - Legge, Sophie E.
AU - Lerer, Bernard
AU - Li, Miaoxin
AU - Li, Tao
AU - Liang, Kung Yee
AU - Lieberman, Jeffrey
AU - Limborska, Svetlana
AU - Loughland, Carmel M.
AU - Lubinski, Jan
AU - Lönnqvist, Jouko
AU - Macek, Milan
AU - Magnusson, Patrik K.E.
AU - Maher, Brion S.
AU - Maier, Wolfgang
AU - Mallet, Jacques
AU - Marsal, Sara
AU - Mattheisen, Manuel
AU - Mattingsdal, Morten
AU - McCarley, Robert W.
AU - McDonald, Colm
AU - McIntosh, Andrew M.
AU - Meier, Sandra
AU - Meijer, Carin J.
AU - Melegh, Bela
AU - Melle, Ingrid
AU - Mesholam-Gately, Raquelle I.
AU - Metspalu, Andres
AU - Michie, Patricia T.
AU - Milani, Lili
AU - Milanova, Vihra
AU - Mokrab, Younes
AU - Morris, Derek W.
AU - Mors, Ole
AU - Murphy, Kieran C.
AU - Murray, Robin M.
AU - Myin-Germeys, Inez
AU - Müller-Myhsok, Bertram
AU - Nelis, Mari
AU - Nenadic, Igor
AU - Nertney, Deborah A.
AU - Nestadt, Gerald
AU - Nicodemus, Kristin K.
AU - Nikitina-Zake, Liene
AU - Nisenbaum, Laura
AU - Nordin, Annelie
AU - O'callaghan, Eadbhard
AU - O'dushlaine, Colm
AU - O'neill, F. Anthony
AU - Oh, Sang Yun
AU - Olincy, Ann
AU - Olsen, Line
AU - Os, Jim Van
AU - Pantelis, Christos
AU - Papadimitriou, George N.
AU - Papiol, Sergi
AU - Parkhomenko, Elena
AU - Pato, Michele T.
AU - Paunio, Tiina
AU - Pejovic-Milovancevic, Milica
AU - Perkins, Diana O.
AU - Pietiläinen, Olli
AU - Pimm, Jonathan
AU - Pocklington, Andrew J.
AU - Powell, John
AU - Price, Alkes
AU - Pulver, Ann E.
AU - Purcell, Shaun M.
AU - Quested, Digby
AU - Rasmussen, Henrik B.
AU - Reichenberg, Abraham
AU - Reimers, Mark A.
AU - Richards, Alexander L.
AU - Roffman, Joshua L.
AU - Roussos, Panos
AU - Ruderfer, Douglas M.
AU - Salomaa, Veikko
AU - Sanders, Alan R.
AU - Schall, Ulrich
AU - Schubert, Christian R.
AU - Schulze, Thomas G.
AU - Schwab, Sibylle G.
AU - Scolnick, Edward M.
AU - Scott, Rodney J.
AU - Seidman, Larry J.
AU - Shi, Jianxin
AU - Sigurdsson, Engilbert
AU - Silagadze, Teimuraz
AU - Silverman, Jeremy M.
AU - Sim, Kang
AU - Slominsky, Petr
AU - Smoller, Jordan W.
AU - So, Hon Cheong
AU - Spencer, Chris C.A.
AU - Stahl, Eli A.
AU - Stefansson, Hreinn
AU - Steinberg, Stacy
AU - Stogmann, Elisabeth
AU - Straub, Richard E.
AU - Strengman, Eric
AU - Strohmaier, Jana
AU - Stroup, T. Scott
AU - Subramaniam, Mythily
AU - Suvisaari, Jaana
AU - Svrakic, Dragan M.
AU - Szatkiewicz, Jin P.
AU - Söderman, Erik
AU - Thirumalai, Srinivas
AU - Toncheva, Draga
AU - Tosato, Sarah
AU - Veijola, Juha
AU - Waddington, John
AU - Walsh, Dermot
AU - Wang, Dai
AU - Wang, Qiang
AU - Webb, Bradley T.
AU - Weiser, Mark
AU - Wildenauer, Dieter B.
AU - Williams, Nigel M.
AU - Williams, Stephanie
AU - Witt, Stephanie H.
AU - Wolen, Aaron R.
AU - Wong, Emily H.M.
AU - Wormley, Brandon K.
AU - Xi, Hualin Simon
AU - Zai, Clement C.
AU - Zheng, Xuebin
AU - Zimprich, Fritz
AU - Stefansson, Kari
AU - Visscher, Peter M.
AU - Adolfsson, Rolf
AU - Andreassen, Ole A.
AU - Blackwood, Douglas H.R.
AU - Bramon, Elvira
AU - Buxbaum, Joseph D.
AU - Børglum, Anders D.
AU - Cichon, Sven
AU - Darvasi, Ariel
AU - Domenici, Enrico
AU - Ehrenreich, Hannelore
AU - Esko, Tõnu
AU - Gejman, Pablo V.
AU - Gill, Michael
AU - Gurling, Hugh
AU - Hultman, Christina M.
AU - Iwata, Nakao
AU - Jablensky, Assen V.
AU - Jönsson, Erik G.
AU - Kendler, Kenneth S.
AU - Kirov, George
AU - Knight, Jo
AU - Lencz, Todd
AU - Levinson, Douglas F.
AU - Li, Qingqin S.
AU - Liu, Jianjun
AU - Malhotra, Anil K.
AU - McCarroll, Steven A.
AU - McQuillin, Andrew
AU - Moran, Jennifer L.
AU - Mortensen, Preben B.
AU - Mowry, Bryan J.
AU - Nöthen, Markus M.
AU - Ophoff, Roel A.
AU - Owen, Michael J.
AU - Palotie, Aarno
AU - Pato, Carlos N.
AU - Petryshen, Tracey L.
AU - Posthuma, Danielle
AU - Rietschel, Marcella
AU - Riley, Brien P.
AU - Rujescu, Dan
AU - Sham, Pak C.
AU - Sklar, Pamela
AU - Clair, David St
AU - Weinberger, Daniel R.
AU - Wendland, Jens R.
AU - Werge, Thomas
AU - Daly, Mark J.
AU - Sullivan, Patrick F.
AU - O'donovan, Michael C.
N1 - Publisher Copyright: © 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85049684948
U2 - 10.1038/s41598-018-28160-z
DO - 10.1038/s41598-018-28160-z
M3 - Article
C2 - 29977057
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 10168
ER -