The Causal Effect of a Genetic Liability for Schizophrenia on the Age at First Birth

There is a well-established empirical association between parental age and children’s well being. Typically, children of teenage parents and parents with a very late age at first birth are worse off in terms of their socio-economic status and (mental) health compared to children of 20-35 years old mothers. So far, this relationship has been attributed to unstable relationships of young parents and their low economic resources as well as the decreasing (physical) health of older parents which, for example, may complicate conception, pregnancy and birth (for an excellent demographic introduction into the topic please check out the dissertation of Alice Goisis at LSE: http://etheses.lse.ac.uk/844/).

In a study, Mehta et al. (2016), we focus on the U-shaped relationship between age at first birth of mothers and their children’s tendency to suffer from schizophrenic syndromes. We consider an alternative explanation for this relationship, namely that a latent liability for schizophrenia has an impact on fertility timing, rather than that early or late fertility leads to a higher risk for schizophrenic symptoms. A liability for schizophrenia can be genetically associated with poor social interactions, which may increase the time taken to find a mate and thereby delay the age at first birth. Schizophrenia risk may also genetically predispose to risk taking and impulsive behavior, which is associated with early pregnancy and childbirth in women.

With the advent of molecular genetic data and complementary analysis tools, it has become possible to test this idea straightforwardly. Our strategy was as follows: We used results from genome-wide-association to generate a genetic risk profile for schizophrenia amongst individuals from an independent fertility sample. The risk for schizophrenia can be constructed as a continuous variable by e.g. summing up alleles that are more frequent amongst schizophrenia cases than amongst controls (we used a more advanced approach, and refer the reader to the manuscript for details). We generated an individual genetic risk score for schizophrenia in a combined dataset of 12,247 genotyped mothers from Estonia, the Netherlands, the United Kingdom and Sweden.

We then checked whether this individual score for schizophrenia is higher amongst women with an early or late age at first birth than for women in a middle range. The Figure below shows that indeed the mean risk profile score was significantly higher in women with early age at first birth (i.e., <20 years) than in women with intermediate age at first birth (P = 8.8E-03 for AFB of 25 to <30 years and P= 1.3E-02 for AFB of 30 to <35 years). The relatively higher schizophrenia risk for older mothers (>40) remains suggestive. We also estimated regression models with a transformed AFB based on results from a previous large-scale study (McGrath et al. 2014), which confirmed our findings.

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Several mechanisms, such as correlation of schizophrenia risk with socioeconomic status and other environmental and biological factors might influence the genetic relationship between schizophrenia and age at first birth, and need to be explored in the future. In summary, this study provides the first evidence for a significant overlap between genetic factors associated with risk of schizophrenia and genetic factors associated with age at first birth.

We consider this study as a neat example of meaningfully incorporating genetic information into social science and demographic studies. In particular: the causal direction between age at first birth and schizophrenia is (at least partly) reversed, compared to what was previously known. Future research that includes social science measures and information on non-genetic factors will facilitate a deeper understanding of causal pathways underlying this association, but the inclusion of genetic information into social sciences appears just as crucial.

References: 

McGrath, J. J., Petersen, L., Agerbo, E., Mors, O., Mortensen, P. B., & Pedersen, C. B. (2014). A comprehensive assessment of parental age and psychiatric disorders. JAMA psychiatry, 71(3), 301–9. doi:10.1001/jamapsychiatry.2013.4081

Mehta, D., Tropf, F. C., Gratten, J., Bakshi, A., Zhu, Z., Bacanu, S.-A., et al. (2016). Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2016.0129


This entry was posted in Fertility, Health by Felix C. Tropf. Bookmark the permalink.
Felix C. Tropf

About Felix C. Tropf

Felix Christian Tropf is a sociologist with the current research focus on social science genetics and the life-course. Since September 2015, he has been working for the Department of Sociology at the University of Oxford as a post-doctoral researcher. He currently is a Research Fellow of Nuffield College.

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