The cystatin C-based Le Bricon equation was the most accurate, and most of the cystatin C-based equations showed improvements in 30% and 50% accuracy compared with the creatinine-based MDRD equation. Cystatin C-based equations may offer an advantage over the MDRD equation in kidney transplant recipients. Estimating equations re-expressed with standardized cystatin C have been developed and their accuracy needs to be tested in the kidney transplant population.

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The evidence underpinning the developmental origins of health and disease (DOHaD) is overwhelming. As the emphasis shifts more towards interventions and the translational strategies for disease prevention, it is important to capitalize on collaboration and knowledge sharing to maximize opportunities for discovery and replication. DOHaD meetings are facilitating this interaction. However, strategies to perpetuate focussed discussions and collaborations around and between conferences are more likely to facilitate the development of DOHaD research. For this reason, the DOHaD Society of Australia and New Zealand (DOHaD ANZ) has initiated themed Working Groups, which convened at the 2014-2015 conferences. This report introduces the DOHaD ANZ Working Groups and summarizes their plans and activities. One of the first Working Groups to form was the ActEarly birth cohort group, which is moving towards more translational goals. Reflecting growing emphasis on the impact of early life biodiversity - even before birth - we also have a Working Group titled Infection, inflammation and the microbiome. We have several Working Groups exploring other major non-cancerous disease outcomes over the lifespan, including Brain, behaviour and development and Obesity, cardiovascular and metabolic health. The Epigenetics and Animal Models Working Groups cut across all these areas and seeks to ensure interaction between researchers. Finally, we have a group focussed on 'Translation, policy and communication' which focusses on how we can best take the evidence we produce into the community to effect change. By coordinating and perpetuating DOHaD discussions in this way we aim to enhance DOHaD research in our region.

Syndrome individual with differential genotoxin sensitivity and a DNA damage response defect, SUMMARY Purpose: Roberts Syndrome (RBS) is a rare recessively-transmitted developmental disorder characterized by growth retardation, craniofacial abnormalities and truncation of limbs. All affected individuals to date have mutations in the ESCO2 (Establishment of cohesion 2) gene, a key regulator of the cohesin complex, which is involved in sister chromatid cohesion and DNA double-strand break (dsb) repair.Here we characterize DNA damage responses (DDRs) for the first time in a RBSaffected family. Methods and Materials: Lymphoblastoid cell lines (LCLs) were established from an RBS family, including the proband, and parents carrying ESCO2 mutations. Various DDR assays were performed on these cells, including clonogenic, chromosome break and apoptosis assays, checkpoint activation indicators and measures of DNA breakage and repair. Results: Cells derived from the RBS-affected individual showed sensitivity to ionizing radiation (IR) and Mitomycin C (MMC) -induced DNA damage. In this ESCO2 compound heterozygote, other DNA damage responses were also defective, including enhanced IR-induced clastogenicity and apoptosis, increased DNA dsb induction and a reduced capacity for repairing IR -induced DNA dsbs as measured by γ-H2AX foci and the comet assay.Conclusions: in addition to its developmental features, RBS can be, like ataxia telangiectasia, considered a DNA damage response-defective syndrome, which contributes to its cellular, molecular and clinical phenotype.

Genetic risk for depressive disorders is poorly understood despite consistent suggestions of a high heritable component. Most genetic studies have focused on risk associated with single variants, a strategy which has so far only yielded small (often non-replicable) risks for depressive disorders. In this paper we argue that more substantial risks are likely to emerge from genetic variants acting in synergy within and across larger neurobiological systems (polygenic risk factors). We show how knowledge of major integrated neurobiological systems provides a robust basis for defining and testing theoretically defensible polygenic risk factors. We do this by describing the architecture of the overall stress response. Maladaptation via impaired stress responsiveness is central to the aetiology of depression and anxiety and provides a framework for a systems biology approach to candidate gene selection. We propose principles for identifying genes and gene networks within the neurosystems involved in the stress response and for defining polygenic risk factors based on the neurobiology of stress-related behaviour. We conclude that knowledge of the neurobiology of the stress response system is likely to play a central role in future efforts to improve genetic prediction of depression and related disorders.

Literature suggests that reading to children can have a significant impact on their early literacy development and long-term school performance. We examine whether consistent participation (i.e., three or more years) in Dolly Parton’s Imagination Library (DPIL), a book distribution program that provides one book per month to children ages birth through five, is associated with higher kindergarten readiness. This study examines 2,731 incoming kindergartners in the Syracuse City School District in 2013 and 2014 using the AIMSweb Letter Naming Fluency (LNF) test to assess kindergarten readiness. LNF is frequently identified as the best single indicator of risk for reading failure and has been shown to have a strong ability to predict future reading, vocabulary, and language development. Examining both the entire population and propensity score matched groups, we find that a significantly higher percentage of those consistently participating in DPIL were considered as ready for kindergarten. This difference remained even after controlling for key demographic variables.

Background and aims Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks. Approach and results We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially methylated CpG sites (dmCpGs) for which ≥ 2 probes per gene remained significant across four statistical models with a nominal p value < 0.007. EWAS identified dmCpGs related to three genes (ANK1, MIR10a, PTPRN2) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced (ANK1 n = 6, MIR10a n = 7, PTPRN2 n = 3), three dmCpGs in ANK1 and two in MIR10a were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in ANK1 remained significant. These ANK1 CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted p < 2.3 × 10–3). Conclusions We identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies. Graphical abstract

BACKGROUND AND AIMS: Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks. APPROACH & RESULTS: We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially-methylated CpG sites (dmCpGs) for which ≥2 probes per gene remained significant across four statistical models with a nominal p-value <0.007. EWAS identified dmCpGs related to three genes (ANK1, MIR10a, PTPRN2) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced (ANK1 n=6, MIR10a n=7, PTPRN2 n=3), three dmCpGs in ANK1 and two in MIR10a were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in ANK1 remained significant. These ANK1 CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted p<2.3 x 10-3). CONCLUSIONS: We identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies.