Please use this identifier to cite or link to this item:
Title: Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women
Contributor(s): Mehta, Divya (author); Tropf, Felix C (author); Metspalu, Andres (author); Snieder, Harold (author); Mowry, Bryan J (author); Kendler, Kenneth S (author); Yang, Jian (author); Visscher, Peter M (author); McGrath, John J (author); Mills, Melinda C (author); Wray, Naomi R (author); Lee, Sang Hong  (author); Gratten, Jacob (author); Bakshi, Andrew (author); Zhu, Zhihong (author); Bacanu, Silviu-Alin (author); Hemani, Gibran (author); Magnusson, Patrik K E (author); Barban, Nicola (author); Esko, Tonu (author)
Publication Date: 2016
Open Access: Yes
DOI: 10.1001/jamapsychiatry.2016.0129Open Access Link
Handle Link:
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.
Publication Type: Journal Article
Grant Details: NHMRC/APP1080157
Source of Publication: JAMA Psychiatry, 73(5), p. E1-E9
Publisher: American Medical Association
Place of Publication: United States of America
ISSN: 2168-6238
Fields of Research (FoR) 2008: 110319 Psychiatry (incl. Psychotherapy)
060408 Genomics
060412 Quantitative Genetics (incl. Disease and Trait Mapping Genetics)
Fields of Research (FoR) 2020: 320221 Psychiatry (incl. psychotherapy)
310509 Genomics
310506 Gene mapping
Socio-Economic Objective (SEO) 2008: 920110 Inherited Diseases (incl. Gene Therapy)
970106 Expanding Knowledge in the Biological Sciences
970111 Expanding Knowledge in the Medical and Health Sciences
Socio-Economic Objective (SEO) 2020: 280102 Expanding knowledge in the biological sciences
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
Appears in Collections:Journal Article

Files in This Item:
2 files
File Description SizeFormat 
Show full item record


checked on May 27, 2023

Page view(s)

checked on Mar 9, 2023
Google Media

Google ScholarTM



Items in Research UNE are protected by copyright, with all rights reserved, unless otherwise indicated.