Research Repository

Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women

Mehta, Divya and Tropf, Felix C and Gratten, Jacob and Bakshi, Andrew and Zhu, Zhihong and Bacanu, Silviu-Alin and Hemani, Gibran and Magnusson, Patrik KE and Barban, Nicola and Esko, Tõnu and Metspalu, Andres and Snieder, Harold and Mowry, Bryan J and Kendler, Kenneth S and Yang, Jian and Visscher, Peter M and McGrath, John J and Mills, Melinda C and Wray, Naomi R and Lee, S Hong and Andreassen, Ole A and Bramon, Elvira and Bruggeman, Richard and Buxbaum, Joseph D and Cairns, Murray J and Cantor, Rita M and Cloninger, C Robert and Cohen, David and Crespo-Facorro, Benedicto and Darvasi, Ariel and DeLisi, Lynn E and Dinan, Timothy and Djurovic, Srdjan and Donohoe, Gary and Drapeau, Elodie and Escott-Price, Valentina and Freimer, Nelson B and Georgieva, Lyudmila and de Haan, Lieuwe and Henskens, Frans A and Joa, Inge and Julià, Antonio and Khrunin, Andrey and Lerer, Bernard and Limborska, Svetlana and Loughland, Carmel M and Macek, Milan and Magnusson, Patrik KE and Marsal, Sara and McCarley, Robert W and McIntosh, Andrew M and McQuillin, Andrew and Melegh, Bela and Michie, Patricia T and Morris, Derek W and Murphy, Kieran C and Myin-Germeys, Inez and Olincy, Ann and Van Os, Jim and Pantelis, Christos and Posthuma, Danielle and Quested, Digby and Schall, Ulrich and Scott, Rodney J and Seidman, Larry J and Toncheva, Draga and Tooney, Paul A and Waddington, John and Weinberger, Daniel R and Weiser, Mark and Wu, Jing Qin (2016) 'Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women.' JAMA Psychiatry, 73 (5). 497 - 505. ISSN 2168-622X

[img]
Preview
Text
yoi160009.pdf - Published Version

Download (233kB) | Preview

Abstract

Importance A recently published study of national data by McGrath et al in 2014 showed increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age, consistent with a U-shaped relationship. However, it remains unclear if the risk to the child is due to psychosocial factors associated with parental age or if those at higher risk for SCZ tend to have children at an earlier or later age. Objective To determine if there is a genetic association between SCZ and age at first birth (AFB) using genetically informative but independently ascertained data sets. Design, Setting, and Participants This investigation used multiple independent genome-wide association study data sets. The SCZ sample comprised 18 957 SCZ cases and 22 673 controls in a genome-wide association study from the second phase of the Psychiatric Genomics Consortium, and the AFB sample comprised 12 247 genotyped women measured for AFB from the following 4 community cohorts: Estonia (Estonian Genome Center Biobank, University of Tartu), the Netherlands (LifeLines Cohort Study), Sweden (Swedish Twin Registry), and the United Kingdom (TwinsUK). Schizophrenia genetic risk for each woman in the AFB community sample was estimated using genetic effects inferred from the SCZ genome-wide association study. Main Outcomes and Measures We tested if SCZ genetic risk was a significant predictor of response variables based on published polynomial functions that described the relationship between maternal age and SCZ risk in offspring in Denmark. We substituted AFB for maternal age in these functions, one of which was corrected for the age of the father, and found that the fit was superior for the model without adjustment for the father’s age. Results We observed a U-shaped relationship between SCZ risk and AFB in the community cohorts, consistent with the previously reported relationship between SCZ risk in offspring and maternal age when not adjusted for the age of the father. We confirmed that SCZ risk profile scores significantly predicted the response variables (coefficient of determination R2 = 1.1E-03, P = 4.1E-04), reflecting the published relationship between maternal age and SCZ risk in offspring by McGrath et al in 2014. Conclusions and Relevance This study provides evidence for a significant overlap between genetic factors associated with risk of SCZ and genetic factors associated with AFB. It has been reported that SCZ risk associated with increased maternal age is explained by the age of the father and that de novo mutations that occur more frequently in the germline of older men are the underlying causal mechanism. This explanation may need to be revised if, as suggested herein and if replicated in future studies, there is also increased genetic risk of SCZ in older mothers.

Item Type: Article
Divisions: Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Elements
Date Deposited: 08 Nov 2019 10:01
Last Modified: 08 Nov 2019 10:01
URI: http://repository.essex.ac.uk/id/eprint/25846

Actions (login required)

View Item View Item