DCC gene network in the prefrontal cortex is associated with total brain volume in childhood

BACKGROUND: Genetic variation in the guidance cue DCC gene is linked to psychopathologies involving dysfunction in the prefrontal cortex. We created an expression-based polygenic risk score (ePRS) based on the DCC coexpression gene network in the prefrontal cortex, hypothesizing that it would be associated with individual differences in total brain volume. METHODS: We filtered single nucleotide polymorphisms (SNPs) from genes coexpressed with DCC in the prefrontal cortex obtained from an adult postmortem donors database (BrainEAC) for genes enriched in children 1.5 to 11 years old (BrainSpan). The SNPs were weighted by their effect size in predicting gene expression in the prefrontal cortex, multiplied by their allele number based on an individual's genotype data, and then summarized into an ePRS. We evaluated associations between the DCC ePRS and total brain volume in children in 2 community-based cohorts: the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) and University of California, Irvine (UCI) projects. For comparison, we calculated a conventional PRS based on a genome-wide association study of total brain volume. RESULTS: Higher ePRS was associated with higher total brain volume in children 8 to 10 years old (β = 0.212, p = 0.043; n = 88). The conventional PRS at several different thresholds did not predict total brain volume in this cohort. A replication analysis in an independent cohort of newborns from the UCI study showed an association between the ePRS and newborn total brain volume (β = 0.101, p = 0.048; n = 80). The genes included in the ePRS demonstrated high levels of coexpression throughout the lifespan and are primarily involved in regulating cellular function. LIMITATIONS: The relatively small sample size and age differences between the main and replication cohorts were limitations. CONCLUSION: Our findings suggest that the DCC coexpression network in the prefrontal cortex is critically involved in whole brain development during the first decade of life. Genes comprising the ePRS are involved in gene translation control and cell adhesion, and their expression in the prefrontal cortex at different stages of life provides a snapshot of their dynamic recruitment

Incorporating Descriptive Metadata into Seismic Source Zone Models for Seismic Hazard Assessment: A case study of the Azores-West Iberian region

In probabilistic seismic-hazard analysis (PSHA), seismic source zone (SSZ) models are widely used to account for the contribution to the hazard from earth- quakes not directly correlated with geological structures. Notwithstanding the impact of SSZ models in PSHA, the theoretical framework underlying SSZ models and the criteria used to delineate the SSZs are seldom explicitly stated and suitably docu- mented. In this paper, we propose a methodological framework to develop and docu- ment SSZ models, which includes (1) an assessment of the appropriate scale and degree of stationarity, (2) an assessment of seismicity catalog completeness-related issues, and (3) an evaluation and credibility ranking of physical criteria used to delin- eate the boundaries of the SSZs. We also emphasize the need for SSZ models to be supported by a comprehensive set of metadata documenting both the unique character- istics of each SSZ and the criteria used to delineate its boundaries. This procedure ensures that the uncertainties in the model can be properly addressed in the PSHA and that the model can be easily updated whenever new data are available. The pro- posed methodology is illustrated using the SSZ model developed for the Azores–West Iberian region in the context of the Seismic Hazard Harmonization in Europe project (project SHARE) and some of the most relevant SSZs are discussed in detail

Plane-symmetric inhomogeneous magnetized viscous fluid universe with a variable Λ\Lambda

The behavior of magnetic field in plane symmetric inhomogeneous cosmological models for bulk viscous distribution is investigated. The coefficient of bulk viscosity is assumed to be a power function of mass density $(\xi =\xi_{0}\rho^{n})$. The values of cosmological constant for these models are found to be small and positive which are supported by the results from recent supernovae Ia observations. Some physical and geometric aspects of the models are also discussed.Comment: 18 pages, LaTex, no figur

Maternal prenatal anxiety and the fetal origins of epigenetic aging

Stress and Psychopatholog

Maternal antenatal depression and child mental health: moderation by genomic risk for attention-deficit/hyperactivity disorder

Maternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture the genotypic influence. We outline a novel approach to describe genomic susceptibility to maternal antenatal depression focusing on child emotional/behavioral difficulties. Two cohorts provided measures of maternal depression, child genetic variation, and child mental health symptoms. We constructed a conventional polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) (PRSADHD) that significantly moderated the association between maternal antenatal depression and internalizing problems at 60 months (p = 2.94 x 10(-4), R-2 = .18). We then constructed an interaction PRS (xPRS) based on a subset of those single nucleotide polymorphisms from the PRSADHD that most accounted for the moderation of the association between maternal antenatal depression and child outcome. The interaction between maternal antenatal depression and this xPRS accounted for a larger proportion of the variance in child emotional/behavioral problems than models based on any PRSADHD (p = 5.50 x 10(-9), R-2 = .27), with similar findings in the replication cohort. The xPRS was significantly enriched for genes involved in neuronal development and synaptic function. Our study illustrates a novel approach to the study of genotypic moderation on the impact of maternal antenatal depression on child mental health and highlights the utility of the xPRS approach. These findings advance our understanding of individual differences in the developmental origins of mental health.Stress and Psychopatholog