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Background: Fucosyltransferase 2 (FUT2) controls the production of digestive and respiratory epithelia of histo-blood group antigens involved in the attachment of pathogens. The aim of our study was to relate FUT2 variants to reported gastrointestinal and respiratory illnesses in infancy., Methods: In the Southampton Women's Survey, FUT2 genetic variants (single-nucleotide polymorphisms [SNPs] rs601338 and rs602662) were genotyped in 1831 infants and related to infant illnesses, after adjustment for sex, breastfeeding duration, and potential confounders., Results: For FUT2 SNP rs601338, the risk ratios for ≥1 bout of diarrhea during ages 6-12 months and ages 12-24 months per additional risk (G) allele were 1.23 (95% confidence interval [CI], 1.08-1.4; P = .002) and 1.41 (95% CI, 1.24-1.61; P = 1.7 × 10-7), respectively; the risk ratio for ≥1 diagnosis of a lower respiratory illness (ie, pneumonia or bronchiolitis) during ages 12-24 months per additional G allele was 2.66 (95% CI, 1.64-4.3; P = .00007). Similar associations were found between rs602662 and gastrointestinal and respiratory illnesses, owing to the high linkage disequilibrium with rs601338 (R2 = 0.92). Longer breastfeeding duration predicted a lower risk of diarrhea, independent of infant FUT2 genotype., Conclusions: We confirmed that FUT2 G alleles are associated with a higher risk of infant gastrointestinal illnesses and identified novel associations with respiratory illnesses. FUT2 locus variants need consideration in future studies of gastrointestinal and respiratory illnesses among infants., (© Crown copyright 2018.)

Context: Single-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation., Objective: To determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation., Design: Within-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation., Setting: Hospital antenatal clinics., Participants: In total, 682 women of white ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped., Interventions: 1000 IU/d cholecalciferol from 14 weeks of gestation until delivery., Main Outcome Measure: 25(OH)D at randomization and 34 weeks of gestation were measured in a single batch (Liaison; Diasorin, Dartford, UK). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [β represents the change in 25(OH)D per additional common allele]., Results: Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [β = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P < 0.004]. In contrast, rs10741657 (CYP2R1) (β = -5.2 nmol/L; 95% CI, -8.2 to -2.2 nmol/L; P = 0.001) and rs2282679 (GC) (β = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; P = 0.01) were associated with achieved 25(OH)D status following supplementation, whereas rs12785878 and rs6013897 (CYP24A1) were not., Conclusions: Genetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity., (Copyright © 2017 Endocrine Society)

Background: Early life environments induce long-term changes in neurocognitive development and behaviour. In animal models, early environmental cues affect neuropsychological phenotypes via epigenetic processes but, as yet, there is little direct evidence for such mechanisms in humans., Method: We examined the relation between DNA methylation at birth and child neuropsychological outcomes in two culturally diverse populations using a genome-wide methylation analysis and validation by pyrosequencing., Results: Within the UK Southampton Women's Survey (SWS) we first identified 41 differentially methylated regions of interest (DMROI) at birth associated with child's full-scale IQ at age 4 years. Associations between HES1 DMROI methylation and later cognitive function were confirmed by pyrosequencing in 175 SWS children. Consistent with these findings, higher HES1 methylation was associated with higher executive memory function in a second independent group of 200 SWS 7-year-olds. Finally, we examined a pathway for this relationship within a Singaporean cohort (n = 108). Here, HES1 DMROI methylation predicted differences in early infant behaviour, known to be associated with academic success. In vitro, methylation of HES1 inhibited ETS transcription factor binding, suggesting a functional role of this site., Conclusions: Thus, our findings suggest that perinatal epigenetic processes mark later neurocognitive function and behaviour, providing support for a role of epigenetic processes in mediating the long-term consequences of early life environment on cognitive development., (© The Author 2015. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Structural variation in the human genome is increasingly recognized as being highly prevalent and having relevance to common human diseases. Array-based comparative genome-hybridization technology can be used to determine copy-number variation (CNV) across entire genomes, and quantitative PCR (qPCR) can be used to validate de novo variation or assays of common CNV in disease-association studies. Analysis of large qPCR data sets can be complicated and time-consuming, however., Methods: We describe qPCR assays for GSTM1 (glutathione S-transferase mu 1) and GSTT1 (glutathione S-transferase theta 1) gene deletions that can genotype up to 192 samples in duplicate 5-microL reaction volumes in <2 h on the ABI Prism 7900HT Sequence Detection System. To streamline data handling and analysis of these CNVs by qPCR, we developed a novel interactive, macro-driven Microsoft Excel(R) spreadsheet. As proof of principle, we used our software to analyze CNV data for 1478 DNA samples from a family-based cohort., Results: With only 8 ng of DNA template, we assigned CNV genotypes (i.e., 2, 1, or 0 copies) to either 96% (GSTM1) or 91% (GSTT1) of all DNA samples in a single round of PCR amplification. Genotyping accuracy, as ascertained by familial inheritance, was >99.5%, and independent genotype assignments with replicate real-time PCR runs were 100% concordant., Conclusions: The genotyping assay for GSTM1 and GSTT1 gene deletion is suitable for large genetic epidemiologic studies and is a highly effective analysis system that is readily adaptable to analysis of other CNVs. .