No abstract

Genetic studies have to date identified 43 genome wide significant coeliac disease susceptibility (CD) loci comprising over 70 candidate genes. However, how altered regulation of such disease associated genes contributes to CD pathogenesis remains to be elucidated. Recently there has been considerable emphasis on characterising cell type specific and stimulus dependent genetic variants. Therefore in this study we used RNA sequencing to profile over 70 transcriptomes of CD4+ T cells, a cell type crucial for CD pathogenesis, in both stimulated and resting samples from individuals with CD and unaffected controls. We identified extensive transcriptional changes across all conditions, with the previously established CD gene IFNy the most strongly up-regulated gene (log2 fold change 4.6; Padjusted = 2.40x10-11) in CD4+ T cells from CD patients compared to controls. We show a significant correlation of differentially expressed genes with genetic studies of the disease to date (Padjusted = 0.002), and 21 CD candidate susceptibility genes are differentially expressed under one or more of the conditions used in this study. Pathway analysis revealed significant enrichment of immune related processes. Co-expression network analysis identified several modules of coordinately expressed CD genes. Two modules were particularly highly enriched for differentially expressed genes (P<2.2x10-16) and highlighted IFNy and the genetically associated transcription factor BACH2 which showed significantly reduced expression in coeliac samples (log2FC -1.75; Padjusted = 3.6x10-3) as key regulatory genes in CD. Genes regulated by BACH2 were very significantly over-represented among our differentially expressed genes (P<2.2x10-16) indicating that reduced expression of this master regulator of T cell differentiation promotes a pro-inflammatory response and strongly corroborates genetic evidence that BACH2 plays an important role in CD pathogenesis.

Objective: Early complementary feeding has been shown to increase the risk of overweight, obesity and chronic diseases later in life. Poor compliance with current guidelines on complementary feeding has been reported by Irish studies. The aim of the present paper is to identify predictors of early complementary feeding in order to help health professionals target population groups in greater need of dietary intervention as well as to provide effective advice. Design: Cross-sectional analysis of the national, longitudinal Growing Up in Ireland study. Setting: Data were derived from the first wave (2007)(2008) of the Growing Up in Ireland infant cohort. Subjects: A cohort of mothers (n 11 134) from the Republic of Ireland, interviewed when their infants were 9 months of age. Results: Of the infants, 1469 (13?5 %) had been regularly taking solids in the period between 12 and 16 weeks; this percentage increased to 47?0 % of the sample in the period between 16 and 20 weeks. Timing of formula feeding commencement, high maternal BMI and choosing a relative as the infant's minder were strongly associated with early introduction of solids both in bivariate and multivariate analysis. Those infants who started formula feeding at .4 months were 88?4% less likely to be introduced to solids early compared with those who started at ,2 months (OR 5 0?116; 95% CI 0?072, 0?186; P , 0?001).Conclusions: The results demonstrate that biological, social and behavioural aspects exert an important role in infant feeding practices. These findings are relevant to the design of policies and intervention programmes aimed at educating parents. Keywords Complementary feedingInfant's diet Early weaningThe European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) defines complementary foods as other solids and liquids introduced into the infant diet apart from breast milk or formula milk (1) . The introduction of complementary foods into an infant's diet is an important process not only for developmental and growth reasons, but also because of its potential long-term effects on health (2)(3)(4)(5)(6)(7)(8)(9)(10)(11) . Providing a balanced diet while adhering to introduction times recommended by guidelines is pivotal during this period of rapid growth, not only because of the high probability of nutritional deficiencies but also because early complementary feeding has been shown by some studies to increase the risk of overweight, obesity and chronic diseases later in life (5,6,(8)(9)(10) . Moreover, the transition from milk to solid foods is a crucial point to establish life-long feeding patterns (11)(12)(13) . However, poor adherence to recommendations on the introduction of complementary foods has been reported in the Republic of Ireland (ROI) as well as internationally (14)(15)(16)(17)(18) . WHO recommends exclusive breast-feeding during the first 6 months of life of the infant, with the gradual introduction of solids after 6 months (19) . The Department of Health and Children in the ROI updated its advice ...

Early nutrition plays a pivotal role in long-term health. The World Health Organization (WHO) recommends exclusive breastfeeding during the first six months of life, with the gradual introduction of solids after this period. However, studies in the Republic of Ireland (ROI) have shown poor compliance with guidelines. The ROI continues to have one of the lowest breastfeeding rates worldwide. Our objective was to analyse differences in breastfeeding and complimentary feeding behaviours between Irish and non-Irish mothers residing in the ROI, as well as the role of acculturation on these behaviours, using the national longitudinal study, Growing Up in Ireland (GUI). Mothers (n = 11,134) residing in the ROI were interviewed when their infants were nine months of age. The percentage of Irish mothers who initiated breastfeeding was 49.5%, as opposed to 88.1% among the non-Irish cohort (p < 0.001). Breastfeeding initiation reduced from 89.4% of non-Irish mothers who had arrived within the last year to five years ago to 67.5% for those who had arrived 11 to >20 years ago (p < 0.001). Our results indicate that cultural differences are an important factor in shaping patterns of infant feeding in the ROI. Reviewing existing support and education policies for parents is required to achieve the implementation of desirable infant feeding practices.