19 research outputs found
Identification of common genetic risk variants for autism spectrum disorder
Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD
Evidence for Increased Genetic Risk Load for Major Depression in Patients Assigned to Electroconvulsive Therapy
Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistant
depression; disorder severity and unfavorable treatment outcomes are shown to be influenced
by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment
and response/nonresponse are associated with an increased genetic burden for major
depression (MD) using polygenic risk score (PRS), which summarize the contribution of diseaserelated
common risk variants. Fifty-one psychiatric inpatients suffering from a major depressive
episode underwent ECT. MD-PRS were calculated for these inpatients and a separate
population-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on summary
statistics from the Psychiatric Genomics Consortium MDD-working group (Cases:
n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease status
between ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higher
MD-PRS. MD-PRS in population-based depression self-reporters were intermediate between
ECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response
(50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate
that ECT cohorts show an increased genetic burden for MD and are consistent with the
hypothesis that treatment-resistant MD patients represent a subgroup with an increased genetic
risk for MD. Larger samples are needed to better substantiate these findings
Clinical efficacy of one year cardiac resynchronization therapy in heart failure patients stratified by QRS duration: results of the PATH-CHF II trial
COMPENSATION STRATEGIES AND EXPORT PERFORMANCE OF SMALL MANUFACTURING FIRMS IN ATLANTIC CANADA
COMPENSATION STRATEGIES AND EXPORT PERFORMANCE OF SMALL MANUFACTURING FIRMS IN ATLANTIC CANADA
Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations
Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
Abstract
Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk
Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk