Investigating interactions between early life stress and two single nucleotide polymorphisms in HSD11B2 on the risk of schizophrenia

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Jean-Christophe Debost, MD, PhD student at National Centre for Research-based Research, Aarhus University

About the study 

Testing gene-environment interactions using register-based data

In a hypothesis-driven study with a not so idiomatic name, we investigated gene environment interactions using register-based data and information on genetics.

Exposure to prenatal stress such as loss or serious illness of close relatives has been shown to be associated with schizophrenia. A theory that accounts for the potential effects of early life stress is ‘‘fetal programming’’. According to this hypothesis, adaptive changes in the fetus in response to changes in the intra-uterine environment such as cortisol overexposure may entail permanent changes in physiology and neuroendocrine structure that predispose the individual to neuropsychiatric illness later in life.

HSD11B2 is the gene encoding the enzyme HSD2 that is responsible for converting cortisol to its inactive derivate in the placenta, and thereby protecting the fetus from excess cortisol.

We genotyped two SNPs that had been associated with altered function of HSD2, and investigated whether the risk of schizophrenia in prenatally stressed children varied according to the genotype.

Our results did not support the hypothesis that the effect of prenatal exposure to stress varied by genotype of the two SNPs. However, this is a good example of how register-based data can be used in a G by E setting to test specific hypotheses.

The article “Investigating interactions between early life stress and two single nucleotide polymorphisms in HSD11B2 on the risk of schizophrenia” was published in Psychoneuroendocrinology 2015 Oct;60:18-27.

Facts about the study

  • The study is based on data derived from the Danish Psychiatric Central Register, the Danish Civil Registration System, and the Danish Neonatal Screening Biobank.
  • We genotyped rs5479 and rs56303414 among 1275 schizophrenia cases and 1367 controls.
  • We investigated interactions between genotypes and early life stress on the risk of schizophrenia.
  • We found no interaction between prenatal exposure to stress and genotype, but the results must be interpreted with caution due to the few exposed cases for each genotype.

Further information

Jean-Christophe Debost, MD, PhD student, National Center for Register-based Research, Aarhus University, email: