scholarly journals Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene–environment interaction. The EUGEI study

2019 ◽  
Vol 50 (11) ◽  
pp. 1884-1897 ◽  
Author(s):  
Jim van Os ◽  
Lotta-Katrin Pries ◽  
Philippe Delespaul ◽  
Gunter Kenis ◽  
Jurjen J. Luykx ◽  
...  
Keyword(s):  
Cognitive Ability ◽  
Psychotic Disorder ◽  
Genetic Risk ◽  
Environment Interaction ◽  
Replication Sample ◽  
Polygenic Risk ◽  
Gene Environment Interaction ◽  
Intermediate Phenotypes ◽  
Gene Environment ◽  
Healthy Siblings

AbstractBackgroundFirst-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.MethodsWe conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.ResultsIn both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.ConclusionsThe degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.

scholarly journals Effect of polygenic risk scores on depression in childhood trauma

2014 ◽  
Vol 205 (2) ◽  
pp. 113-119 ◽  
Author(s):  
Wouter J. Peyrot ◽  
Yuri Milaneschi ◽  
Abdel Abdellaoui ◽  
Patrick F. Sullivan ◽  
Jouke J. Hottenga ◽  
...  
Keyword(s):  
Childhood Trauma ◽  
Meta Analysis ◽  
Genetic Effect ◽  
Risk Scores ◽  
Environment Interaction ◽  
Polygenic Risk ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Genome Wide ◽  
Direct Genetic Effect

BackgroundResearch on gene×environment interaction in major depressive disorder (MDD) has thus far primarily focused on candidate genes, although genetic effects are known to be polygenic.AimsTo test whether the effect of polygenic risk scores on MDD is moderated by childhood trauma.MethodThe study sample consisted of 1645 participants with a DSM-IV diagnosis of MDD and 340 screened controls from The Netherlands. Chronic or remitted episodes (severe MDD) were present in 956 participants. The occurrence of childhood trauma was assessed with the Childhood Trauma Interview and the polygenic risk scores were based on genome-wide meta-analysis results from the Psychiatric Genomics Consortium.ResultsThe polygenic risk scores and childhood trauma independently affected MDD risk, and evidence was found for interaction as departure from both multiplicativity and additivity, indicating that the effect of polygenic risk scores on depression is increased in the presence of childhood trauma. The interaction effects were similar in predicting all MDD risk and severe MDD risk, and explained a proportion of variation in MDD risk comparable to the polygenic risk scores themselves.ConclusionsThe interaction effect found between polygenic risk scores and childhood trauma implies that (1) studies on direct genetic effect on MDD gain power by focusing on individuals exposed to childhood trauma, and that (2) individuals with both high polygenic risk scores and exposure to childhood trauma are particularly at risk for developing MDD.

scholarly journals Genetic Risk for Schizophrenia, Obstetric Complications, and Adolescent School Outcome: Evidence for Gene-Environment Interaction

2012 ◽  
Vol 39 (5) ◽  
pp. 1067-1076 ◽  
Author(s):  
Jennifer K. Forsyth ◽  
Lauren M. Ellman ◽  
Antti Tanskanen ◽  
Ulla Mustonen ◽  
Matti O. Huttunen ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Obstetric Complications ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
School Outcome

scholarly journals The effects of polygenic risk for psychiatric disorders and smoking behaviour on psychotic experiences in UK Biobank

2019 ◽  
Author(s):  
Judit García-González ◽  
Julia Ramírez ◽  
David M. Howard ◽  
Caroline H Brennan ◽  
Patricia B. Munroe ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Genetic Risk ◽  
Maternal Smoking ◽  
Smoking Status ◽  
Smoking Behaviour ◽  
Environment Interaction ◽  
Uk Biobank ◽  
Psychotic Experiences ◽  
Gene Environment Interaction ◽  
Gene Environment

ABSTRACTWhile psychotic experiences are core symptoms of mental health disorders like schizophrenia, they are also reported by 5-10% of the population. Both smoking behaviour and genetic risk for psychiatric disorders have been associated with psychotic experiences, but the interplay between these factors remains poorly understood. We tested whether smoking status, maternal smoking around birth, and number of packs smoked/year were associated with lifetime occurrence of three psychotic experiences phenotypes: delusions (n=2067), hallucinations (n=6689), and any psychotic experience (delusions or hallucinations; n=7803) in 144818 UK Biobank participants. We next calculated polygenic risk scores for schizophrenia (PRSSCZ), major depression (PRSDEP) and attention deficit hyperactivity disorder (PRSADHD) in the UK Biobank participants to assess whether association between smoking and psychotic experiences was attenuated after adjustment of diagnosis of psychiatric disorders and the PRSs. Finally, we investigated whether smoking exacerbates the effects of genetic predisposition on the psychotic phenotypes in gene-environment interaction models. Smoking status, maternal smoking, and number of packs smoked/year were significantly associated with psychotic experiences (p<1.77×10−5). Except for packs smoked/year, effects were attenuated but remained significant after adjustment for diagnosis of psychiatric disorders and PRSs (p<1.99×10−3). Gene-environment interaction models showed the effects of PRSDEP and PRSADHD(but not PRSSCZ) on delusions (but not hallucinations) were significantly greater in current smokers compared to never smokers (p<0.0028). There were no significant gene-environment interactions for maternal smoking nor for number of packs smoked/year. Our results suggest that both genetic risk of psychiatric disorders and smoking status may have independent and synergistic effects on specific types of psychotic experiences.

The Effect of Prenatal Valproate Exposure in Serotonin Transporter Knockout Rats On Anxiety and Cognition: A Gene*Environment Interaction Model of Autism Spectrum Disorder

2021 ◽  
Author(s):  
◽  
Caren L. August
Keyword(s):  
Autism Spectrum Disorder ◽  
Cognitive Ability ◽  
Serotonin Transporter ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Starting Point

<p>Autism Spectrum Disorder is a complex neurodevelopmental disorder which is often associated with increased anxiety and deficits in cognitive ability. The present research investigated a potential gene*environment interaction between two factors previously implicated in ASD in a rat model; prenatal exposure to valproate (VPA) and genetic reduction of the serotonin transporter (SERT). Wildtype and heterozygous SERT knockout rats prenatally exposed to VPA or saline on gestational day12.5 (G12.5) were assessed on measures of anxiety: elevated plus-maze and novelty suppressed-feeding and cognitive ability: prepulse inhibition and latent inhibition. A significant main effect was found for VPA exposure in all paradigms, showing increased anxiety-typical behaviour and abnormal cognitive ability. However, no significant effect of genotype or interaction was observed. Results from the present study do not confirm gene*environment interaction between prenatal VPA and heterozygous SERT knockout but this may be due to several factors that are discussed within the thesis. In any case, this study represents a starting point for further studies investigating other combinations of genetic and environmental factors as models of ASD pathogenesis.</p>

scholarly journals Encode and a new landscape for psychiatric genetics

2013 ◽  
Vol 203 (2) ◽  
pp. 84-85 ◽  
Author(s):  
Akshay Nair ◽  
Robert Howard
Keyword(s):  
Gene Regulation ◽  
Environment Interaction ◽  
Psychiatric Genetics ◽  
Encode Project ◽  
Polygenic Risk ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Rigorous Research ◽  
Dna Elements ◽  
Insight Into

SummaryDespite rigorous research into the genetics of neuropsychiatric disorders, the mechanism by which polygenic risk leads to complex clinical phenotypes remains unclear. The Encyclopedia of DNA Elements (ENCODE) project gives us new insight into gene regulation, and gene–gene and gene–environment interaction.Better understanding of these key genomic mechanisms may provide the answers we have been searching for.

Genetic and environmental pathways to suicidal behavior: Reflections of a genetic epidemiologist

2010 ◽  
Vol 25 (5) ◽  
pp. 300-303 ◽  
Author(s):  
K.S. Kendler
Keyword(s):  
Psychiatric Disorders ◽  
Suicidal Behavior ◽  
Indirect Effects ◽  
Genetic Risk ◽  
Developmental Pathways ◽  
Early Adversity ◽  
Environment Interaction ◽  
Direct Effects ◽  
Gene Environment Interaction ◽  
Gene Environment

AbstractThis paper presents a tentative typology of genetic and environmental pathways to suicidal behavior. Ten pathways are proposed and briefly illustrated: (i) direct effects from psychiatric disorders; (ii) direct effects from personality; (iii) direct effects of early adversity; (iv) direct effects of current adversity; (v) indirect effects of genes on selection into adversity (gene–environment correlation); (vi) interactions between genetic risk and current adversity: gene–environment interaction; (vii) interactions between early and current adversity: environment–environment interaction; (viii) interactions between culture and genes; (ix) dynamic developmental pathways involving causal loops from genes to environment and back again; and (x) gene × environment × development interaction.

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