Search Results (17)

The association between newborn DNA methylation (DNAm) and asthma acquisition (AA) during adolescence has been suggested. Lung function (LF) has been shown to be associated with asthma risk and its severity. However, the role of LF in the associations between DNAm and AA is unclear, and it is also unknown whether the association between DNAm and AA is consistent with that between DNAm and LF. We address this question through assessing newborn epigenetic features of preadolescence LF and of AA during adolescence, along with their biological pathways and processes. Our study’s primary medical significance lies in advancing the understanding of asthma’s early life origins. By investigating epigenetic markers in newborns and their association with lung function in preadolescence, we aim to uncover potential early biomarkers of asthma risk. This could facilitate earlier detection and intervention strategies. Additionally, exploring biological pathways linking early lung function to later asthma development can offer insights into the disease’s pathogenesis, potentially leading to novel therapeutic targets. Methods: The study was based on the Isle of Wight Birth cohort (IOWBC). Female subjects with DNAm data at birth and with no asthma at age 10 years were included (n = 249). The R package ttScreening was applied to identify CpGs potentially associated with AA from 10 to 18 years and with LF at age 10 (FEV1, FVC, and FEV1/FVC), respectively. Agreement in identified CpGs between AA and LF was examined, along with their biological pathways and processes via the R function gometh. We tested the findings in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), to examine overall replicability. Results: In IOWBC, 292 CpGs were detected with DNAm associated with AA and 1517 unique CpGs for LF (514 for FEV1, 436 for FVC, 408 for FEV1/FVC), with one overlapping CpG, cg23642632 (NCKAP1) between AA and LF. Among the IOWBC-identified CpGs, we further tested in ALSPAC and observed the highest agreement between the two cohorts in FVC with respect to the direction of association and statistical significance. Epigenetic enrichment analyses indicated non-specific connections in the biological pathways and processes between AA and LF. Conclusions: The present study suggests that FEV1, FVC, and FEV1/FVC (as objective measures of LF) and AA (incidence of asthma) are likely to have their own specific epigenetic features and biological pathways at birth. More replications are desirable to fully understand the complexity between DNAm, lung function, and asthma acquisition. Full article

Reported associations of pre-pregnancy weight and/or gestational weight gain with offspring behavioural outcomes are inconsistent. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), this study aimed to examine these associations at five developmental stages between the ages of 3 and 16. Over 6800 mother–offspring pairs at age 3 and 3925 pairs at age 16 were included. Pre-pregnancy underweight was associated with a 22% increased risk of total behavioural difficulties (OR = 1.22, 95% CI 1.02–1.45). In separate analyses using the SDQ subscales, pre-pregnancy underweight was linked to a 37% (OR = 1.37, 95% CI 1.14–1.65) and 33% (OR = 1.33, 95% CI 1.01–1.76) increased risk of emotional symptoms and prosocial behaviour problems over time, respectively. While pre-pregnancy overweight was associated with an 11% (OR = 1.11, 95% CI 1.03–1.20) and 18% (OR = 1.18, 95% CI 1.03–1.36) increased risk of conduct and peer relationship problems, respectively, pregnancy obesity was associated with a 43% increased risk of emotional problems (OR = 1.43, 95% CI 1.16–1.77). We found no evidence of associations between gestational weight gain and child behaviour except for a reduced risk in prosocial behaviour problems (OR = 0.82, 95% CI 0.70–0.96). Our findings provide insights into the link between preconception BMI and child behaviour, underscoring the necessity for further research to validate these associations and elucidate underlying mechanisms. Full article

Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total N = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing ~3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the β-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (p-values < 3.09 × 10⁻⁶; CDH17, TAS2R43, SMIM10L1, TAS2R14). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by TAS2R14, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, Streptococcus mutans and Staphylococcus aureus. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes. Full article

Objectives: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), this study aimed to replicate the finding of the Etude Longitudinale Alimentation Nutrition Croissance des Enfants (ELANCE) that low fat intake in early childhood was associated with increased adiposity in adulthood. Methods: Diet was assessed at 8 and 18 months using 3-day food records. Body composition variables were measured at 9 and 17 years, and serum leptin at 9 years. Associations were modelled using adjusted linear regression. Results: In replication analyses, in contrast to ELANCE, there was a positive association between fat intake (% energy) at 18 months and fat mass (FM) at 9 years (B coefficient 0.10 (95% CI 0.03, 0.20) kg, p = 0.005). There was no association with serum leptin. In extended analyses fat intake at 18 months was positively associated with FM in boys (0.2 (0.00, 0.30), p = 0.008) at 9 years but not in girls. Fat intake was positively associated with serum leptin concentration in boys (0.2 (0.1, 0.4) ng/mL, p = 0.011) but not in girls. Conclusions: Our results did not corroborate the findings from the ELANCE study. A high fat diet in early life may have implications for later childhood and adolescent obesity. Full article

Background: Breastfeeding is associated with short and long-term health benefits. Long-term effects might be mediated by epigenetic mechanisms, yet the literature on this topic is scarce. We performed the first epigenome-wide association study of infant feeding, comparing breastfed vs non-breastfed children. We measured DNA methylation in children from peripheral blood collected in childhood (age 7 years, N = 640) and adolescence (age 15–17 years, N = 709) within the Accessible Resource for Integrated Epigenomic Studies (ARIES) project, part of the larger Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Cord blood methylation (N = 702) was used as a negative control for potential pre-natal residual confounding. Results: Two differentially-methylated sites presented directionally-consistent associations with breastfeeding at ages 7 and 15–17 years, but not at birth. Twelve differentially-methylated regions in relation to breastfeeding were identified, and for three of them there was evidence of directional concordance between ages 7 and 15–17 years, but not between birth and age 7 years. Conclusions: Our findings indicate that DNA methylation in childhood and adolescence may be predicted by breastfeeding, but further studies with sufficiently large samples for replication are required to identify robust associations. Full article

This cross-sectional study aims to assess the influence of maternal smoking and alcohol consumption during pregnancy on the facial shape of non-syndromic English adolescents and demonstrate the potential benefits of using multilevel principal component analysis (mPCA). A cohort of 3755 non-syndromic 15-year-olds from the Avon Longitudinal Study of Parents and Children (ALSPAC), England, were included. Maternal smoking and alcohol consumption during the 1st and 2nd trimesters of pregnancy were determined via questionnaire at 18 weeks gestation. 21 facial landmarks, used as a proxy for the main facial features, were manually plotted onto 3D facial scans of the participants. The effect of maternal smoking and maternal alcohol consumption (average 1–2 glasses per week) was minimal, with 0.66% and 0.48% of the variation in the 21 landmarks of non-syndromic offspring explained, respectively. This study provides a further example of mPCA being used effectively as a descriptive analysis in facial shape research. This is the first example of mPCA being extended to four levels to assess the influence of environmental factors. Further work on the influence of high/low levels of smoking and alcohol and providing inferential evidence is required. Full article

Background: Disordered eating (DE) is common and is associated with body mass index (BMI). We investigated whether genetic variants for BMI were associated with DE. Methods: BMI polygenic scores (PGS) were calculated for participants of the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 8654) and their association with DE tested. Data on DE behaviors (e.g., binge eating and compensatory behaviors) were collected at ages 14, 16, 18 years, and DE cognitions (e.g., body dissatisfaction) at 14 years. Mediation analyses determined whether BMI mediated the association between the BMI-PGS and DE. Results: The BMI-PGS was positively associated with fasting (OR = 1.42, 95% CI = 1.25, 1.61), binge eating (OR = 1.28, 95% CI = 1.12, 1.46), purging (OR = 1.20, 95% CI = 1.02, 1.42), body dissatisfaction (Beta = 0.99, 95% CI = 0.77, 1.22), restrained eating (Beta = 0.14, 95% CI = 0.10, 1.17), emotional eating (Beta = 0.21, 95% CI = 0.052, 0.38), and negatively associated with thin ideal internalization (Beta = −0.15, 95% CI = −0.23, −0.07) and external eating (Beta = −0.19, 95% CI = −0.30, −0.09). These associations were mainly mediated by BMI. Conclusions: Genetic variants associated with BMI are also associated with DE. This association was mediated through BMI suggesting that weight potentially sits on the pathway from genetic liability to DE. Full article

Few studies have investigated the extent to which diet predicts body Cd concentrations among women of reproductive age, and pregnant women in particular. The aim of this study was to examine diet as a predictor of blood Cd concentrations in pregnant women participating in the UK Avon Longitudinal Study of Parents and Children (ALSPAC). Whole blood samples were analysed for Cd (median 0.26 (IQR 0.14–0.54) µg/L). Dietary pattern scores were derived from principal components analysis of data from a food frequency questionnaire. Associations between dietary pattern scores and foods/food groups with blood Cd ≥ median value were identified using adjusted logistic regression (n = 2169 complete cases). A health conscious dietary pattern was associated with a reduced likelihood of B-Cd ≥0.26 µg/l (OR 0.56 (95% CI 0.39–0.81)). There were similarly reduced likelihoods for all leafy green and green vegetables (0.72 (0.56–0.92) when consumed ≥4 times/week vs ≤1 to ≥3 times/week) and with all meats (0.66 (0.46–0.95) when consumed ≥4 times/week vs ≤ once in 2 weeks). Sensitivity analysis excluding smokers showed similar results. The evidence from this study provides continued support for a healthy and varied diet in pregnancy, incorporating foods from all food groups in accordance with national recommendations, without the need for specific guidance. Full article

Breastfeeding has long-term benefits for children that may be mediated via the epigenome. This pathway has been hypothesized, but the number of empirical studies in humans is small and mostly done by using peripheral blood as the DNA source. We performed an epigenome-wide association study (EWAS) in buccal cells collected around age nine (mean = 9.5) from 1006 twins recruited by the Netherlands Twin Register (NTR). An age-stratified analysis examined if effects attenuate with age (median split at 10 years; n_<10 = 517, mean age = 7.9; n_>10 = 489, mean age = 11.2). We performed replication analyses in two independent cohorts from the NTR (buccal cells) and the Avon Longitudinal Study of Parents and Children (ALSPAC) (peripheral blood), and we tested loci previously associated with breastfeeding in epigenetic studies. Genome-wide DNA methylation was assessed with the Illumina Infinium MethylationEPIC BeadChip (Illumina, San Diego, CA, USA) in the NTR and with the HumanMethylation450 Bead Chip in the ALSPAC. The duration of breastfeeding was dichotomized (‘never‘ vs. ‘ever’). In the total sample, no robustly associated epigenome-wide significant CpGs were identified (α = 6.34 × 10^–8). In the sub-group of children younger than 10 years, four significant CpGs were associated with breastfeeding after adjusting for child and maternal characteristics. In children older than 10 years, methylation differences at these CpGs were smaller and non-significant. The findings did not replicate in the NTR sample (n = 98; mean age = 7.5 years), and no nearby sites were associated with breastfeeding in the ALSPAC study (n = 938; mean age = 7.4). Of the CpG sites previously reported in the literature, three were associated with breastfeeding in children younger than 10 years, thus showing that these CpGs are associated with breastfeeding in buccal and blood cells. Our study is the first to show that breastfeeding is associated with epigenetic variation in buccal cells in children. Further studies are needed to investigate if methylation differences at these loci are caused by breastfeeding or by other unmeasured confounders, as well as what mechanism drives changes in associations with age. Full article

This synopsis paper aims to identify if a common pattern of learning and social difficulties can be conceptualized across recent longitudinal studies investigating the influence of mild-to-moderate gestational iodine deficiency (GID) on offspring’s optimal cognitive and psycho-social development. The main studies investigated are: The Southampton Women’s Study (SWS)—United Kingdom; the Avon Longitudinal Study of Parents and Children (ALSPAC)—United Kingdom; the Gestational Iodine Cohort Longitudinal Study—Tasmania, Australia, and the Danish National Birth Cohort Case-Control Study—Denmark. In contrast to severe GID where there is a global negative impact on neurodevelopment, mild-to-moderate intrauterine iodine deficiency has subtler, but nonetheless important, permanent cognitive and psycho-social consequences on the offspring. This paper links the results from each study and maintains that mild-to-moderate GID is associated with a disorder that is characterized by speed of neural transmitting difficulties that are typically associated with working memory capacity difficulties and attention and response inhibition. The authors maintain that this disorder is better identified as Gestational Iodine Deficiency Processing Disorder (GIDPD), rather than, what to date has often been identified as ‘suboptimal development’. The Autistic Spectrum Disorder (ASD), Attention Deficit, Hyperactivity Disorder (ADHD), language and literacy disorders (learning disabilities and dyslexia) are the main manifestations associated with GIDPD. GIDPD is identified on IQ measures, but selectively and mainly on verbal reasoning IQ subtests, with individuals with GIDPD still operating within the ‘normal’ full-scale IQ range. Greater consideration needs to be given by public health professionals, policy makers and educators about the important and preventable consequences of GID. Specifically, more emphasis should be placed on adequate iodine intake in women prior to pregnancy, as well as during pregnancy and when lactating. Secondly, researchers and others need to further extend, refine and clarify whether GIDPD, as a nosological (medical classification) entity, is a valid disorder and concept for consideration. Full article

Picky eating has been associated with lower intakes of some nutrients and foods during preschool ages but there is little known about the longer-term diet. The aim of this study was to characterise the diets of children aged 10 and 13 years who had been identified as: (1) picky eaters at age 3 years (cross-sectional); and (2) picky eaters at 2–5.5 years old (longitudinal). Picky eating behaviour (PE) was identified in the Avon Longitudinal Study of Parents and Children (ALSPAC) from parental/caregiver questionnaires. Dietary intake was assessed at age 3.5 years and repeated at 10 and 13 years. For cross-sectional PE compared with non-PE there were differences at age 10 years that were similar to those at 3.5 years: lower intakes of protein (−5%) and fibre (−7%) and of meat (−15%), fruit (−10%) and vegetables (−33%). At 13 years, differences in vegetable (−23%), fruit (−14%) and meat (−8%) intakes were evident. For longitudinal (persistent) PE, differences were more pronounced at each age. More effective strategies to help parents to widen the food choices of their children at early ages need to be developed, focusing particularly on vegetable and fruit intakes. Full article

The relationship between mitochondrial DNA (mtDNA) and breast cancer has been frequently examined, particularly in European populations. However, studies reporting associations between mtDNA haplogroups and breast cancer risk have had a few shortcomings including small sample sizes, failure to account for population stratification and performing inadequate statistical tests. In this study we investigated the association of mtDNA haplogroups of European origin with several breast cancer risk factors in mothers and children of the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort that enrolled over 14,000 pregnant women in the Southwest region of the UK. Risk factor data were obtained from questionnaires, clinic visits and blood measurements. Information on over 40 independent breast cancer risk factor-related variables was available for up to 7781 mothers and children with mtDNA haplogroup data in ALSPAC. Linear and logistic regression models adjusted for age, sex and population stratification principal components were evaluated. After correction for multiple testing we found no evidence of association of European mtDNA haplogroups with any of the breast cancer risk factors analysed. Mitochondrial DNA haplogroups are unlikely to underlie susceptibility to breast cancer that occurs via the risk factors examined in this study of a population of European ancestry. Full article

Severe iodine deficiency during pregnancy has been associated with pregnancy/neonatal loss, and adverse pregnancy outcomes; however, the impact of mild–to–moderate iodine insufficiency, though prevalent in pregnancy, is not well-documented. We assessed whether mild iodine deficiency during pregnancy was associated with pregnancy/infant loss, or with other adverse pregnancy outcomes. We used samples and data from the Avon Longitudinal Study of Parents and Children (ALSPAC), from 3140 singleton pregnancies and from a further 42 women with pregnancy/infant loss. The group was classified as mildly-to-moderately iodine deficient with a median urinary iodine concentration of 95.3 µg/L (IQR 57.0–153.0; median urinary iodine-to-creatinine ratio (UI/Creat) 124 µg/g, IQR 82–198). The likelihood of pregnancy/infant loss was not different across four UI/Creat groups (<50, 50–149, 150–250, >250 µg/g). The incidence of pre-eclampsia, non-proteinuric gestational hypertension, gestational diabetes, glycosuria, anaemia, post-partum haemorrhage, preterm delivery, mode of delivery, being small for gestational age, and large for gestational age did not differ significantly among UI/Creat groups, nor were there any significant differences in the median UI/Creat. We conclude that maternal iodine status was not associated with adverse pregnancy outcomes in a mildly-to-moderately iodine-deficient pregnant population. However, in view of the low number of women with pregnancy/infant loss in our study, further research is required. Full article

Y-chromosomal (Y-DNA) haplogroups are more widely used in population genetics than in genetic epidemiology, although associations between Y-DNA haplogroups and several traits, including cardiometabolic traits, have been reported. In apparently homogeneous populations defined by principal component analyses, there is still Y-DNA haplogroup variation which will result from population history. Therefore, hidden stratification and/or differential phenotypic effects by Y-DNA haplogroups could exist. To test this, we hypothesised that stratifying individuals according to their Y-DNA haplogroups before testing for associations between autosomal single nucleotide polymorphisms (SNPs) and phenotypes will yield difference in association. For proof of concept, we derived Y-DNA haplogroups from 6537 males from two epidemiological cohorts, Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 5080; 816 Y-DNA SNPs) and the 1958 Birth Cohort (n = 1457; 1849 Y-DNA SNPs), and studied the robust associations between 32 SNPs and body mass index (BMI), including SNPs in or near Fat Mass and Obesity-associated protein (FTO) which yield the strongest effects. Overall, no association was replicated in both cohorts when Y-DNA haplogroups were considered and this suggests that, for BMI at least, there is little evidence of differences in phenotype or SNP association by Y-DNA structure. Further studies using other traits, phenome-wide association studies (PheWAS), other haplogroups and/or autosomal SNPs are required to test the generalisability and utility of this approach. Full article

Alcohol problems represent a classic example of a complex behavioral outcome that is likely influenced by many genes of small effect. A polygenic approach, which examines aggregate measured genetic effects, can have predictive power in cases where individual genes or genetic variants do not. In the current study, we first tested whether polygenic risk for alcohol problems—derived from genome-wide association estimates of an alcohol problems factor score from the age 18 assessment of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4304 individuals of European descent; 57% female)—predicted alcohol problems earlier in development (age 14) in an independent sample (FinnTwin12; n = 1162; 53% female). We then tested whether environmental factors (parental knowledge and peer deviance) moderated polygenic risk to predict alcohol problems in the FinnTwin12 sample. We found evidence for both polygenic association and for additive polygene-environment interaction. Higher polygenic scores predicted a greater number of alcohol problems (range of Pearson partial correlations 0.07–0.08, all p-values ≤ 0.01). Moreover, genetic influences were significantly more pronounced under conditions of low parental knowledge or high peer deviance (unstandardized regression coefficients (b), p-values (p), and percent of variance (R²) accounted for by interaction terms: b = 1.54, p = 0.02, R² = 0.33%; b = 0.94, p = 0.04, R² = 0.30%, respectively). Supplementary set-based analyses indicated that the individual top single nucleotide polymorphisms (SNPs) contributing to the polygenic scores were not individually enriched for gene-environment interaction. Although the magnitude of the observed effects are small, this study illustrates the usefulness of polygenic approaches for understanding the pathways by which measured genetic predispositions come together with environmental factors to predict complex behavioral outcomes. Full article