Evidence for genetic overlap between schizophrenia and age at first birth in women
<h4>Importance:</h4> <p>A recent published study of national data 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 p...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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American Medical Association
2016
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| _version_ | 1797090917982666752 |
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| author | Tropf, F Mills, M Barban, N Mehta, D Gratten, J Bakshi, A Zhu, Z Bacanu, S Hermani, G Magnusson, P Esko, T Metspalu, A Snieder, H Mowry, B Kendler, K Yang, J Visscher, P McGrath, J Wray, N Lee, S Schizophrenia Working Group of the Psychiatric Genomics Consortium LifeLines Cohort Study TwinsUK |
| author_facet | Tropf, F Mills, M Barban, N Mehta, D Gratten, J Bakshi, A Zhu, Z Bacanu, S Hermani, G Magnusson, P Esko, T Metspalu, A Snieder, H Mowry, B Kendler, K Yang, J Visscher, P McGrath, J Wray, N Lee, S Schizophrenia Working Group of the Psychiatric Genomics Consortium LifeLines Cohort Study TwinsUK |
| author_sort | Tropf, F |
| collection | OXFORD |
| description | <h4>Importance:</h4> <p>A recent published study of national data 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.</p> <h4>Objective:</h4> <p>To determine if there is a genetic association between SCZ and age at first birth (AFB) using genetically informative but independently ascertained data sets.</p> <h4>Design, Setting, and Participants:</h4> <p>We used genome-wide association study (GWAS) data from 18,957 SCZ cases and 22,673 controls and from 12,247 women from independent community samples not enriched for psychiatric disorders measured for AFB. SCZ genetic risk for each woman in the AFB sample was estimated using genetic effects inferred from the SCZ GWAS.</p> <h4>Main Outcomes and Measures:</h4> <p>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 age of the father, and found that the fit was superior in the model without adjustment for father's age.</p> <h4>Results:</h4> <p>We observed a U-shaped relationship between SCZ risk and AFB, consistent with the previously reported relationship between SCZ risk in offspring and maternal age when not adjusted for age of the father. We confirmed that SCZ risk profile score significantly predicted the response variables reflecting the published relationship between maternal age and SCZ risk in offspring from McGrath et al. (2014) (pvalue=4E-04).</p> <h4>Conclusions and Relevance:</h4> <p>It has been reported that SCZ risk associated with increased maternal age is explained by 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 here, and if replicated in future studies, there is also an increased genetic risk of SCZ in older mothers. </p> |
| first_indexed | 2024-03-07T03:25:33Z |
| format | Journal article |
| id | oxford-uuid:b8e82e08-38a2-4c32-b966-dbe90dc74cb2 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T03:25:33Z |
| publishDate | 2016 |
| publisher | American Medical Association |
| record_format | dspace |
| spelling | oxford-uuid:b8e82e08-38a2-4c32-b966-dbe90dc74cb22022-03-27T04:59:18ZEvidence for genetic overlap between schizophrenia and age at first birth in womenJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b8e82e08-38a2-4c32-b966-dbe90dc74cb2Symplectic Elements at OxfordAmerican Medical Association2016Tropf, FMills, MBarban, NMehta, DGratten, JBakshi, AZhu, ZBacanu, SHermani, GMagnusson, PEsko, TMetspalu, ASnieder, HMowry, BKendler, KYang, JVisscher, PMcGrath, JWray, NLee, SSchizophrenia Working Group of the Psychiatric Genomics ConsortiumLifeLines Cohort StudyTwinsUK<h4>Importance:</h4> <p>A recent published study of national data 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.</p> <h4>Objective:</h4> <p>To determine if there is a genetic association between SCZ and age at first birth (AFB) using genetically informative but independently ascertained data sets.</p> <h4>Design, Setting, and Participants:</h4> <p>We used genome-wide association study (GWAS) data from 18,957 SCZ cases and 22,673 controls and from 12,247 women from independent community samples not enriched for psychiatric disorders measured for AFB. SCZ genetic risk for each woman in the AFB sample was estimated using genetic effects inferred from the SCZ GWAS.</p> <h4>Main Outcomes and Measures:</h4> <p>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 age of the father, and found that the fit was superior in the model without adjustment for father's age.</p> <h4>Results:</h4> <p>We observed a U-shaped relationship between SCZ risk and AFB, consistent with the previously reported relationship between SCZ risk in offspring and maternal age when not adjusted for age of the father. We confirmed that SCZ risk profile score significantly predicted the response variables reflecting the published relationship between maternal age and SCZ risk in offspring from McGrath et al. (2014) (pvalue=4E-04).</p> <h4>Conclusions and Relevance:</h4> <p>It has been reported that SCZ risk associated with increased maternal age is explained by 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 here, and if replicated in future studies, there is also an increased genetic risk of SCZ in older mothers. </p> |
| spellingShingle | Tropf, F Mills, M Barban, N Mehta, D Gratten, J Bakshi, A Zhu, Z Bacanu, S Hermani, G Magnusson, P Esko, T Metspalu, A Snieder, H Mowry, B Kendler, K Yang, J Visscher, P McGrath, J Wray, N Lee, S Schizophrenia Working Group of the Psychiatric Genomics Consortium LifeLines Cohort Study TwinsUK Evidence for genetic overlap between schizophrenia and age at first birth in women |
| title | Evidence for genetic overlap between schizophrenia and age at first birth in women |
| title_full | Evidence for genetic overlap between schizophrenia and age at first birth in women |
| title_fullStr | Evidence for genetic overlap between schizophrenia and age at first birth in women |
| title_full_unstemmed | Evidence for genetic overlap between schizophrenia and age at first birth in women |
| title_short | Evidence for genetic overlap between schizophrenia and age at first birth in women |
| title_sort | evidence for genetic overlap between schizophrenia and age at first birth in women |
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