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Gene-environment interaction study on the polygenic risk score for neuroticism, childhood adversity, and parental bonding.

ABSTRACT: The present study examines whether neuroticism is predicted by genetic vulnerability, summarized as polygenic risk score for neuroticism (PRS_N), in interaction with bullying, parental bonding, and childhood adversity. Data were derived from a general population adolescent and young adult twin cohort. The final sample consisted of 202 monozygotic and 436 dizygotic twins and 319 twin pairs. The Short Eysenck Personality questionnaire was used to measure neuroticism. PRS_N was trained on the results from the Genetics of Personality Consortium (GPC) and United Kingdom Biobank (UKB) cohorts, yielding two different PRS_N. Multilevel mixed-effects models were used to analyze the main and interacting associations of PRS_N, childhood adversity, bullying, and parental bonding style with neuroticism. We found no evidence of gene-environment correlation. PRS_N thresholds of .005 and .2 were chosen, based on GPC and UKB datasets, respectively. After correction for confounders, all the individual variables were associated with the expression of neuroticism: both PRS_N from GPC and UKB, childhood adversity, maternal bonding, paternal bonding, and bullying in primary school and secondary school. However, the results indicated no evidence for gene-environment interaction in this cohort. These results suggest that genetic vulnerability on the one hand and negative life events (childhood adversity and bullying) and positive life events (optimal parental bonding) on the other represent noninteracting pathways to neuroticism.

SUBMITTER: Klingenberg B

PROVIDER: S-EPMC10725776 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Gene-environment interaction study on the polygenic risk score for neuroticism, childhood adversity, and parental bonding.

Klingenberg Boris B Guloksuz Sinan S Pries Lotta-Katrin LK Cinar Ozan O Menne-Lothmann Claudia C Decoster Jeroen J van Winkel Ruud R Collip Dina D Delespaul Philippe P De Hert Marc M Derom Catherine C Thiery Evert E Jacobs Nele N Wichers Marieke M Lin Bochao D BD Luykx Jurjen J van Os Jim J Rutten Bart P F BPF

Personality neuroscience 20230804

The present study examines whether neuroticism is predicted by genetic vulnerability, summarized as polygenic risk score for neuroticism (PRSN), in interaction with bullying, parental bonding, and childhood adversity. Data were derived from a general population adolescent and young adult twin cohort. The final sample consisted of 202 monozygotic and 436 dizygotic twins and 319 twin pairs. The Short Eysenck Personality questionnaire was used to measure neuroticism. PRSN< ...[more]

PMID: 38107775

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Project description:Stress-sensitivity (SS) is considered a psychobiological trait possibly resulting from the interaction of genetic and environmental factors (GxE). This study examined whether the interaction of SS-related genetic markers with interview-based dimensions of childhood adversity predicted longitudinal trajectories of low versus high SS. Participants were nonclinically-ascertained young adults comprising normative and elevated scores on schizotypy. SS trajectories were defined in a previous report based on three prospective assessments (23.5, 25, 28 years-old) of both retrospective (Perceived Stress Scale; PSS) and momentary (Experience Sampling Methodology; ESM) stress ratings. A total of n = 177 and n = 165 participants with PSS and ESM stress-sensitivity trajectories, respectively, as well as genetic data, were included in the study. GxE effects between a SS Polygenic Risk Score (PRS-SS) and a Genetic Risk Score of the Hypothalamic Pituitary Adrenal axis (GRS-HPA) with childhood adversity dimensions (Intrafamilial Adversity, Threat and Deprivation) on SS trajectories were examined. Threat was the most consistent predictor of persistently high SS. PRS-SS moderated the association of Threat with high-PSS. GRS-HPA moderated the effects of all adversity dimensions on high-PSS. The interaction of PRS-SS with Deprivation and GRS-HPA with Intrafamilial Adversity predicted trajectories of momentary social stress, but the effects were driven by those with lower genetic susceptibility. Genetic-HPA-axis moderates the effects of all adversity dimensions on persistent SS trajectories, as well as PRS-SS and Threat, particularly for retrospective stress measure. The findings highlight the complex interplay between GxE factors and suggest that PSS may better capture SS trait. Including biologically-meaningful GRS indexing SS and adversity dimensions in future studies using comprehensive stress measures would enhance our knowledge on high SS susceptibility and its relationship with diverse psychopathological outcomes.

Project description:While the co-morbidity between metabolic and psychiatric behaviors is well-established, the mechanisms are poorly understood, and exposure to early life adversity (ELA) is a common developmental risk factor. ELA is associated with altered insulin sensitivity and poor behavioral inhibition throughout life, which seems to contribute to the development of metabolic and psychiatric disturbances in the long term. We hypothesize that a genetic background associated with higher fasting insulin interacts with ELA to influence the development of executive functions (e.g., impulsivity in young children). We calculated the polygenic risk scores (PRSs) from the genome-wide association study (GWAS) of fasting insulin at different thresholds and identified the subset of single nucleotide polymorphisms (SNPs) that best predicted peripheral insulin levels in children from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort [N = 467; p t- initial = 0.24 (10,296 SNPs), p t- refined = 0.05 (57 SNPs)]. We then calculated the refined PRS (rPRS) for fasting insulin at this specific threshold in the children from the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) cohort and investigated its interaction effect with adversity on an impulsivity task applied at 36 months. We found a significant effect of interaction between fasting insulin rPRS and adversity exposure predicting impulsivity measured by the Snack Delay Task at 36 months [β = -0.329, p = 0.024], such that higher PRS [β = -0.551, p = 0.009] was linked to more impulsivity in individuals exposed to more adversity. Enrichment analysis (MetaCoreTM) of the SNPs that compose the fasting insulin rPRS at this threshold was significant for certain nervous system development processes including dopamine D2 receptor signaling. Additional enrichment analysis (FUMA) of the genes mapped from the SNPs in the fasting insulin rPRS showed enrichment with the accelerated cognitive decline GWAS. Therefore, the genetic background associated with risk for adult higher fasting insulin moderates the impact of early adversity on childhood impulsivity.

Dataset Information

Gene-environment interaction study on the polygenic risk score for neuroticism, childhood adversity, and parental bonding.

Publications

Gene-environment interaction study on the polygenic risk score for neuroticism, childhood adversity, and parental bonding.

Similar Datasets

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