Epigenome-wide Analysis Identifies Genes and Pathways Linked to Neurobehavioral Variation in Preterm Infants
SCIENTIFIC REPORTS
Authors: Everson, Todd M.; Marsit, Carmen J.; O'Shea, T. Michael; Burt, Amber; Hermetz, Karen; Carter, Brian S.; Helderman, Jennifer; Hofheimer, Julie A.; McGowan, Elisabeth C.; Neal, Charles R.; Pastyrnak, Steven L.; Smith, Lynne M.; Soliman, Antoine; DellaGrotta, Sheri A.; Dansereau, Lynne M.; Padbury, James F.; Lester, Barry M.
Abstract
Neonatal molecular biomarkers of neurobehavioral responses (measures of brain-behavior relationships), when combined with neurobehavioral performance measures, could lead to better predictions of long-term developmental outcomes. To this end, we examined whether variability in buccal cell DNA methylation (DNAm) associated with neurobehavioral profiles in a cohort of infants born less than 30 weeks postmenstrual age (PMA) and participating in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study (N = 536). We tested whether epigenetic age, age acceleration, or DNAm levels at individual loci differed between infants based on their NICU Network Neurobehavioral Scale (NNNS) profile classifications. We adjusted for recruitment site, infant sex, PMA, and tissue heterogeneity. Infants with an optimally well-regulated NNNS profile had older epigenetic age compared to other NOVI infants (beta(1) = 0.201, p-value = 0.026), but no significant difference in age acceleration. In contrast, infants with an atypical NNNS profile had differential methylation at 29 CpG sites (FDR < 10%). Some of the genes annotated to these CpGs included PLA2G4E, TRIM9, GRIK3, and MACROD2, which have previously been associated with neurological structure and function, or with neurobehavioral disorders. These findings contribute to the existing evidence that neonatal epigenetic variations may be informative for infant neurobehavior.
Family-based and case-control association studies of glutamate receptor GRIK3 Ser310Ala polymorphism in Polish patients and families with alcohol dependence
NEUROSCIENCE LETTERS
Authors: Samochowiec, J; Grzywacz, A; Kucharska-Mazur, J; Samochowiec, A; Horodnicki, J; Pelka-Wysiecka, J; Syrek, S
Abstract
The aim of this study was to evaluate the role of the GRIK3 functional polymorphism (Ser310Ala) in the pathogenesis of alcoholism. This polymorphism was investigated in two types of studies: (1) the association study in a whole group of alcoholics (116 patients fulfilling ICD-10 alcohol dependence (AD) criteria and 255 controls, Polish descent) and homogenous overlapping subgroups of patients with: a history of delirium tremens and/or alcohol seizures, early age of onset of alcoholism (AOO < 26 years), a co-occurrence of dissocial personality disorder, a history of familial alcoholism; (2) the family-based study (using Transmission Disequilibrium Test (TDT) in 100 Polish families with alcohol dependence). The history of alcoholism was obtained using SSAGA (Polish version). GRIK3 functional polymorphism was determined using PCR. TDT revealed an adequate transmission of both alleles to the affected offspring in the whole group of alcohol families (29 x Ser, 24 x Ala; chi(2) = 0.472; d.f. = 1; p=0.492) and in the homogenous subgroups of families. No significant associations between any of the above mentioned alcohol phenotypes and Ser310 allele were observed (the whole AD group: p = 0.66 AD with delirium and/or seizures: p = 0.521; early onset AD: p = 0.868; AD with familial history of alcoholism: p = 0.798 and AD with dissocial personality disorder: p = 0.618). These findings do not seem to support the hypothesis of the role of this polymorphism in the pathogenesis of alcoholism. (c) 2005 Elsevier Ireland Ltd. All rights reserved.