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Issue no. 3

Serious mental illness and disrupted caregiving for children - a nationwide, register-based cohort study

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Anne Ranning, MSc in Psychology, PhD student at Mental Health Centre Copenhagen

Some parents with mental disorders have serious difficulties with caregiving for their children. In some cases social services place the child in out-of-home care with the purpose of protecting children from harm and ensuring children’s needs. In this study we investigated the association between parents’ diagnosis of schizophrenia, bipolar disorder and depression and placement of children in out-of-home care. Risks for child-placements were especially high if the mother suffered from schizophrenia, of which 40% of children were placed in care during childhood, hereof 20% by the first year of life. The study adds to the evidence of childhood adversities for children at high risk for serious mental illness. Read more.

Linkage and whole genome sequencing identify a locus on 6q25–26 for formal thought disorder and implicate MEF2A regulation

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Johan Thygesen, PhD in Psychiatry, psychiatric genetics research associate at University College London, Division of Psychiatry

Through linkage analysis and subsequent fine-mapping with whole genomes sequencing we identify a rare high-risk variant for formal thought disorder, a key symptom of schizophrenia. The study was performed on the Copenhagen Schizophrenia Linkage Study, a unique family sample describing six large pedigrees heavily affected with schizophrenia. The implicated variant was found to segregate in 31 member of the same pedigree, and was predicted to disrupt the binding of the transcription factor MEF2A between the two previously described schizophrenia genes QKI and PED10A. Read more.

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 Register-based Research, Aarhus University

In a hypothesis-driven study with a not so idiomatic name, we investigated gene environment interactions using register-based data and information on genetics. According to the “fetal programming 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 poor function of HSD2, and investigated whether the risk of schizophrenia in prenatally stressed children varied according to the genotype of these SNPs. Due to a rare exposure, genotype and outcome, the results themselves are of limited value. However, this is a good example of how register-based data can be used in G × E setting to test specific hypotheses. Read more.

Polygenic Risk Score, Parental Socioeconomic Status, Family History of Psychiatric Disorders, and the Risk for Schizophrenia

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Esben Agerbo, professor at National Centre for Register-based Research & CIRRAU, Aarhus University

We used Denmark’s population-based registers, the Danish Neonatal Screening Biobank, and separate metadata from the largest published schizophrenia genome-wide association study to pursue the following questions: (1) How strongly is the risk for schizophrenia related to the mutual effect of the polygenic risk score, parental socioeconomic status, and family history of mental disorders? (2) In theory, what fraction of cases could be prevented if no one was exposed to these factors? (3) Do familial backgrounds interact with an individual’s genetic liability so that specific subgroups of individuals are particularly risk prone? (4) How much of an excess risk associated with familial background is mediated through the offspring’s genetic makeup? Read more

Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores

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Bjarni J Vilhjalmsson, postdoc at Bioinformatics Research Centre, Aarhus University

This paper presents LDpred, a novel Bayesian method for calculating polygenic risk scores, which increases accuracy over current approaches. LDpred achieves this by accounting for linkage disequilibrium and using a prior for the genetic architecture. When applied to real datasets we observed 25% increase in prediction accuracy for schizophrenia, and 30% increase in prediction accuracy for height. Read more.

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