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BACKGROUND: Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear. METHODS: We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1-11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points. RESULTS: We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values

BackgroundAmong children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits.MethodsWe performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5-10 years from 8 cohorts (n = 4268).ResultsIn newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p

BackgroundDNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits.MethodsWe examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment.ResultsDNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni

Background: Few studies have explored the association between DNA methylation and physical activity. The aim of this study was to evaluate the association of objectively measured hours of sedentary behavior (SB) and moderate physical activity (MPA) with DNA methylation. We further aimed to explore the association between SB or MPA related CpG sites and cardiometabolic traits, gene expression, and genetic variation. Results: For discovery, we performed cross sectional analyses in pregnant women from the Epigenetics in pregnancy (EPIPREG) sample with both DNA methylation (Illumina MethylationEPIC BeadChip) and objectively measured physical activity data (SenseWear™ Pro 3 armband) (European = 244, South Asian = 109). For EWAS of SB and MPA, two main models were designed: model (1) a linear mixed model adjusted for age, smoking, blood cell composition, including ancestry as random intercept, and model (2) which was additionally adjusted for the total number of steps per day. In model 1, we did not identify any CpG sites associated with neither SB nor MPA. In model 2, SB was positively associated (false discovery rate, FDR < 0.05) with two CpG sites within the VSX1 gene. Both CpG sites were positively associated with BMI and were associated with several genetic variants in cis. MPA was associated with 122 significant CpG sites at FDR < 0.05 (model 2). We further analyzed the ten most statistically significant MPA related CpG sites and found that they presented opposite associations with sedentary behavior and BMI. We were not able to replicate the SB and MPA-related CpG sites in the Avon Longitudinal Study of Parents and Children (ALSPAC). ALSPAC had available objectively measured physical activity data from Actigraph (without steps/day available) and leucocyte DNA methylation data collected during adolescence (n = 408, European). Conclusion: This study suggests associations of objectively measured SB and MPA with maternal DNA methylation in peripheral blood leukocytes, that needs to be confirmed in larger samples of similar study design. [ABSTRACT FROM AUTHOR]

BackgroundTo examine methylation of the peroxisome proliferator-activated receptor γ (PPARγ) gene and its relationship with child weight status, at birth and 9 years.MethodsWe measured PPARγ methylation across 23 CpG sites using the Infinium Illumina 450 k array for children from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort at birth (N = 373) and 9 years (N = 245).ResultsMethylation level correlation patterns across the 23 PPARγ CpG sites were conserved between birth and 9-year ages. We found high inter-CpG correlations between sites 1-3 (methylation block 1) and also between sites 18-23 (methylation block 2) for both time points, although these patterns were less pronounced at 9 years. Additionally, sites 1-3 (north shore) had the highest intra-CpG correlations over time (r = 0.24, 0.42, and 0.3; P = 0.002, P

BackgroundGenetic data are known to harbor information about human demographics, and genotyping data are commonly used for capturing ancestry information by leveraging genome-wide differences between populations. In contrast, it is not clear to what extent population structure is captured by whole-genome DNA methylation data.ResultsWe demonstrate, using three large-cohort 450K methylation array data sets, that ancestry information signal is mirrored in genome-wide DNA methylation data and that it can be further isolated more effectively by leveraging the correlation structure of CpGs with cis-located SNPs. Based on these insights, we propose a method, EPISTRUCTURE, for the inference of ancestry from methylation data, without the need for genotype data.ConclusionsEPISTRUCTURE can be used to infer ancestry information of individuals based on their methylation data in the absence of corresponding genetic data. Although genetic data are often collected in epigenetic studies of large cohorts, these are typically not made publicly available, making the application of EPISTRUCTURE especially useful for anyone working on public data. Implementation of EPISTRUCTURE is available in GLINT, our recently released toolset for DNA methylation analysis at: http://glint-epigenetics.readthedocs.io.

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (

Epigenetic changes such as DNA methylation may be a molecular mechanism through which environmental exposures affect health. Phthalates are known endocrine disruptors with ubiquitous exposures in the general population including pregnant women, and they have been linked with a number of adverse health outcomes. We examined the association between in utero phthalate exposure and altered patterns of cord blood DNA methylation in 336 Mexican-American newborns. Concentrations of 11 phthalate metabolites were analyzed in maternal urine samples collected at 13 and 26 weeks gestation as a measure of fetal exposure. DNA methylation was assessed using the Infinium HumanMethylation 450K BeadChip adjusting for cord blood cell composition. To identify differentially methylated regions (DMRs) that may be more informative than individual CpG sites, we used two different approaches, DMRcate and comb-p. Regional assessment by both methods identified 27 distinct DMRs, the majority of which were in relation to multiple phthalate metabolites. Most of the significant DMRs (67%) were observed for later pregnancy (26 weeks gestation). Further, 51% of the significant DMRs were associated with the di-(2-ethylhexyl) phthalate metabolites. Five individual CpG sites were associated with phthalate metabolite concentrations after multiple comparisons adjustment (FDR), all showing hypermethylation. Genes with DMRs were involved in inflammatory response (IRAK4 and ESM1), cancer (BRCA1 and LASP1), endocrine function (CNPY1), and male fertility (IFT140, TESC, and PRDM8). These results on differential DNA methylation in newborns with prenatal phthalate exposure provide new insights and targets to explore mechanism of adverse effects of phthalates on human health. Environ. Mol. Mutagen. 58:398-410, 2017. © 2017 Wiley Periodicals, Inc.

BackgroundCharacterization of the epigenome is a primary interest for children's environmental health researchers studying the environmental influences on human populations, particularly those studying the role of pregnancy and early-life exposures on later-in-life health outcomes.ObjectivesOur objective was to consider the state of the science in environmental epigenetics research and to focus on DNA methylation and the collective observations of many studies being conducted within the Children's Environmental Health and Disease Prevention Research Centers, as they relate to the Developmental Origins of Health and Disease (DOHaD) hypothesis.MethodsWe address the current laboratory and statistical tools available for epigenetic analyses, discuss methods for validation and interpretation of findings, particularly when magnitudes of effect are small, question the functional relevance of findings, and discuss the future for environmental epigenetics research.DiscussionA common finding in environmental epigenetic studies is the small-magnitude epigenetic effect sizes that result from such exposures. Although it is reasonable and necessary that we question the relevance of such small effects, we present examples in which small effects persist and have been replicated across populations and across time. We encourage a critical discourse on the interpretation of such small changes and further research on their functional relevance for children's health.ConclusionThe dynamic nature of the epigenome will require an emphasis on future longitudinal studies in which the epigenome is profiled over time, over changing environmental exposures, and over generations to better understand the multiple ways in which the epigenome may respond to environmental stimuli.

Phthalates are frequently used in personal care products and plasticizers and phthalate exposure is ubiquitous in the US population. Exposure to phthalates during critical periods in utero has been associated with a variety of adverse health outcomes but the biological mechanisms linking these exposures with disease are not well characterized. In this study, we examined the relationship of in utero phthalate exposure with repetitive element DNA methylation, an epigenetic marker of genome instability, in children from the longitudinal birth cohort CHAMACOS. Methylation of Alu and long interspersed nucleotide elements (LINE-1) was determined using pyrosequencing of bisulfite-treated DNA isolated from whole blood samples collected from newborns and 9 year old children (n=355). Concentrations of eleven phthalate metabolites were measured in urine collected from pregnant mothers at 13 and 26 weeks gestation. We found a consistent inverse association between prenatal concentrations of monoethyl phthalate, the most frequently detected urinary metabolite, with cord blood methylation of Alu repeats (β(95%CI): -0.14 (-0.28,0.00) and -0.16 (-0.31, -0.02)) for early and late pregnancy, respectively, and a similar but weaker association with LINE-1 methylation. Additionally, increases in urinary concentrations of di-(2-ethylhexyl) phthalate metabolites during late pregnancy were associated with lower levels of methylation of Alu repeats in 9 year old blood (significant p-values ranged from 0.003 to 0.03). Our findings suggest that prenatal exposure to some phthalates may influence differences in repetitive element methylation, highlighting epigenetics as a plausible biological mechanism through which phthalates may affect health.

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.

Confounding by cellular heterogeneity has become a major concern for epigenome-wide association studies (EWAS) in peripheral blood samples from population and clinical studies. Adjusting for white blood cell percentage estimates produced by the minfi implementation of the Houseman algorithm (minfi) during statistical analysis is now an established method to account for this bias in adults. However, minfi has not been benchmarked against white blood cell counts in children that may differ substantially from the reference dataset used in its estimation. We compared estimates of white blood cell type percentages produced by two methods, minfi and differential cell count (DCC), in a birth cohort at two time points (birth and 12 years of age). We found that both minfi and DCC had similar trends as children aged, and neither count method differed by sex among newborns (P > 0.10). However, minfi estimates did not correlate well with DCC in samples from newborns (ρ = -0.05 for granulocytes; ρ = -0.03 for lymphocytes). In older children, correlation improved substantially (ρ = 0.77 for granulocytes; ρ = 0.75 for lymphocytes), likely due to increasing similarity with minfi's adult reference data as children aged. Our findings suggest that the minfi method may provide suitable estimates of white blood cell composition for samples from adults and older children, but may not currently be appropriate for EWAS involving newborns or young children.

BackgroundDNA methylation is an important epigenetic mark that can potentially link early life exposures to adverse health outcomes later in life. Host factors like sex and age strongly influence biological variation of DNA methylation, but characterization of these relationships is still limited, particularly in young children.MethodsIn a sample of 111 Mexican-American subjects (58 girls , 53 boys), we interrogated DNA methylation differences by sex at birth using the 450 K BeadChip in umbilical cord blood specimens, adjusting for cell composition.ResultsWe observed that ~3% of CpG sites were differentially methylated between girls and boys at birth (FDR P

Recent genome- and epigenome-wide studies demonstrate that the DNA methylation is controlled in part by genetics, highlighting the importance of integrating genetic and epigenetic data. To better understand molecular mechanisms affecting gene expression, we used the candidate susceptibility gene paraoxonase 1 (PON1) as a model to assess associations of PON1 genetic polymorphisms with DNA methylation and arylesterase activity, a marker of PON1 expression. PON1 has been associated with susceptibility to obesity, cardiovascular disease, and pesticide exposure. In this study, we assessed DNA methylation in 18 CpG sites located along PON1 shores, shelves, and its CpG island in blood specimens collected from newborns and 9-year-old children participating (n = 449) in the CHAMACOS birth cohort study. The promoter polymorphism, PON1-108 , was strongly associated with methylation, particularly for CpG sites located near the CpG island (P << 0.0005). Among newborns, these relationships were even more pronounced after adjusting for blood cell composition. We also observed significant decreases in arylesterase activity with increased methylation at the same nine CpG sites at both ages. Using causal mediation analysis, we found statistically significant indirect effects of methylation (β(95% confidence interval): 6.9(1.5, 12.4)) providing evidence that DNA methylation mediates the relationship between PON1-108 genotype and PON1 expression. Our findings show that integration of genetic, epigenetic, and expression data can shed light on the functional mechanisms involving genetic and epigenetic regulation of candidate susceptibility genes like PON1.

Epigenetic control of gene expression in children remains poorly understood, but new technologies can help elucidate the relationship between expression and DNA methylation. Here, we utilized the nCounter Analysis System to characterise the expression of 60 genes in 69 9-year-old children from a cohort with a high prevalence of obesity. nCounter expression levels ranged broadly (from 3 to over 10000 messenger RNA counts) and were divided into four categories: high (>2000 counts), moderate (200-1000 counts), low (100-200 counts) and marginal (

Low birth weight is associated with exposure to air pollution during pregnancy. The purpose of this study was to evaluate whether null polymorphisms of Glutathione S-transferases (GSTs), specifically GSTM1 and GSTT1 genes in infants or mothers, modify the association between high exposures to household air pollution (HAP) from cooking fires and birth weight. Pregnant women in rural Guatemala were randomized to receive a chimney stove or continue to use open fires for cooking. Newborns were measured within 48 h of birth. 132 mother-infant pairs provided infant genotypes (n=130) and/or maternal genotypes (n=116). Maternal null GSTM1 was associated with a 144 g (95% CI, -291, 1) and combined maternal/infant null GSTT1 was associated with a 155 g (95% CI, -303, -8) decrease in birth weight. Although there was a trend toward higher birth weights with increasing number of expressed GST genes, the effect modification by chimney stove use was not demonstrated.

In Central America, the traditional temazcales or wood-fired steam baths, commonly used by many Native American populations, are often heated by wood fires with little ventilation, and this use results in high wood smoke exposure. Urinary mutagenicity has been previously employed as a non-invasive biomarker of human exposure to combustion emissions. This study examined the urinary mutagenicity in 19 indigenous Mayan families from the highlands of Guatemala who regularly use temazcales (N = 32), as well as control (unexposed) individuals from the same population (N = 9). Urine samples collected before and after temazcal exposure were enzymatically deconjugated and extracted using solid-phase extraction. The creatinine-adjusted mutagenic potency of urine extracts was assessed using the plate-incorporation version of the Salmonella mutagenicity assay with strain YG1041 in the presence of exogenous metabolic activation. The post-exposure mutagenic potency of urine extracts were, on average, 1.7-fold higher than pre-exposure samples (P < 0.005) and also significantly more mutagenic than the control samples (P < 0.05). Exhaled carbon monoxide (CO) was ~10 times higher following temazcal use (P < 0.0001), and both CO level and time spent in temazcal were positively associated with urinary mutagenic potency (i.e. P < 0.0001 and P = 0.01, respectively). Thus, the wood smoke exposure associated with temazcal use contributes to increased excretion of conjugated mutagenic metabolites. Moreover, urinary mutagenic potency is correlated with other metrics of exposure (i.e. exhaled CO, duration of exposure). Since urinary mutagenicity is a biomarker associated with genetic damage, temazcal use may therefore be expected to contribute to an increased risk of DNA damage and mutation, effects associated with the initiation of cancer.

Epigenetic changes such as DNA methylation may be a molecular mechanism through which environmental exposures affect health. Methylation of Alu and long interspersed nucleotide elements (LINE-1) is a well-established measure of DNA methylation often used in epidemiologic studies. Yet, few studies have examined the effects of host factors on LINE-1 and Alu methylation in children. We characterized the relationship of age, sex, and prenatal exposure to persistent organic pollutants (POPs), dichlorodiphenyl trichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and polybrominated diphenyl ethers (PBDEs), with DNA methylation in a birth cohort of Mexican-American children participating in the CHAMACOS study. We measured Alu and LINE-1 methylation by pyrosequencing bisulfite-treated DNA isolated from whole blood samples collected from newborns and nine-year old children (n = 358). POPs were measured in maternal serum during late pregnancy. Levels of DNA methylation were lower in nine-year olds compared to newborns and were higher in boys compared to girls. Higher prenatal DDT/E exposure was associated with lower Alu methylation at birth, particularly after adjusting for cell type composition (P = 0.02 for o,p' -DDT). Associations of POPs with LINE-1 methylation were only identified after examining the co-exposure of DDT/E with PBDEs simultaneously. Our data suggest that repeat element methylation can be an informative marker of epigenetic differences by age and sex and that prenatal exposure to POPs may be linked to hypomethylation in fetal blood. Accounting for co-exposure to different types of chemicals and adjusting for blood cell types may increase sensitivity of epigenetic analyses for epidemiological studies.

What is already known about this subjectMexican-American children are at particularly high risk of obesity. Features of the perinatal environment, including maternal nutrition, anthropometry, glucose tolerance and growth rate during infancy are implicated in programming of obesity in the offspring.What this study addsGreater rate of weight or length gain in the first 6 months of life is associated with lower 9-year child adiponectin levels, adjusting for 9-year child BMI. Nine-year-old child adipokine levels are strongly related to those of their mothers'.ObjectivesTo (i) determine whether perinatal factors (including maternal anthropometry and nutrition and early life growth measures) are associated with adiponectin and leptin levels in 9-year-old children, and (ii) assess relationships between adiponectin, leptin and concurrent lipid profile in these children.MethodsWe measured plasma adiponectin and leptin for 146 mothers-9-year-old child pairs from the ongoing longitudinal birth cohort followed by the Center for the Health Assessment of Mothers and Children of Salinas. Data on perinatal factors, including sociodemographics, maternal anthropometry and nutrition, and early life child growth were collected during pregnancy, birth and 6-month visits.ResultsGreater rate of weight and length gain during the first 6 months of life were associated with lower adiponectin in 9-year-olds (β = -2.0, P = 0.04; β = -8.2, P = 0.02, respectively) adjusting for child body mass index (BMI). We found no associations between child adipokine levels and either maternal calorie, protein, total fat, saturated fat, fibre, sugar-sweetened beverage consumption during pregnancy or children's concurrent sugar-sweetened beverage and fast food intake. Lipid profile in 9-year-old children closely reflected adiponectin but not leptin levels after adjustment for child BMI. Additionally, we report that child adipokine levels were closely related to their mothers' levels at the 9-year visit.ConclusionOverall, our results support the hypothesis that early life factors may contribute to altered adipokine levels in children.

Analysis of epigenetic mechanisms, particularly DNA methylation, is of increasing interest for epidemiologic studies examining disease etiology and impacts of environmental exposures. The Infinium HumanMethylation450 BeadChip(®) (450K), which interrogates over 480,000 CpG sites and is relatively cost effective, has become a popular tool to characterize the DNA methylome. For large-scale studies, minimizing technical variability and potential bias is paramount. The goal of this paper was to evaluate the performance of several existing and novel color channel normalizations designed to reduce technical variability and batch effects in 450K analysis from a large population study. Comparative assessment of 10 normalization procedures included the GenomeStudio(®) Illumina procedure, the lumi smooth quantile approach, and the newly proposed All Sample Mean Normalization (ASMN). We also examined the performance of normalizations in combination with correction for the two types of Infinium chemistry utilized on the 450K array. We observed that the performance of the GenomeStudio(®) normalization procedure was highly variable and dependent on the quality of the first sample analyzed in an experiment, which is used as a reference in this procedure. While the lumi normalization was able to decrease batch variability, it increased variation among technical replicates, potentially reducing biologically meaningful findings. The proposed ASMN procedure performed consistently well, both at reducing batch effects and improving replicate comparability. In summary, the ASMN procedure can improve existing color channel normalization, especially for large epidemiologic studies, and can be successfully implemented to enhance a 450K DNA methylation data pipeline.

ObjectivesTo address molecular mechanisms underlying obesity development, we examined patterns of critical metabolism-related hormones, adiponectin and leptin (adipokines), over childhood.Subjects and designPlasma adiponectin and leptin were measured in 80 Mexican-American children at birth and again at 2, 5, and 9 years from the ongoing prospective cohort followed by the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS). We used a mixture modeling approach to identify patterns in adipokine trajectories from birth to 9 years.ResultsLeptin was positively related to child body size within all ages, however adiponectin had inverse and weaker associations with BMI at 2, 5, and 9 years. Correlations between adipokine levels over the 0-2, 2-5, and 5-9-year periods increased for both leptin (r = 0.06, 0.31 and 0.62) and adiponectin (r = 0.25, 0.41 and 0.46). Our mixture modeling approach identified three trajectory clusters for both leptin (1L [slowly-rising], 2L [rapidly-rising], and 3L [stable]) and adiponectin (1A [steep-dropping and rebounding], 2A [moderately-dropping], and 3A [stable]). While leptin groups were most separated over the 2-9-year period, adiponectin trajectories displayed greatest heterogeneity from birth to 2 years. Children in the rapidly-rising 2L group had highest BMI and waist circumference at 9 years. Further, children with greater birth weight had increased odds of belonging to this high risk group (OR = 1.21 95% CI 1.03, 1.43, compared to stable group 3L). Children whose mothers consumed more sugar-sweetened beverages during pregnancy were at risk of being in the steep-dropping 1A group (OR = 1.08, 95% CI 1.01, 1.17, compared to stable group 3A).ConclusionOur results highlight developmental differences in leptin and adiponectin over the childhood period. Leptin closely reflects child body size however factors affecting adiponectin and long-term consequences of its changes over infancy need to be further explored.

The correction notice for the article "Epigenome-wide association study of objectively measured physical activity in peripheral blood leukocytes" in BMC Genomics addresses an error in the affiliations section, specifically the addition of a missing affiliation for "Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK." The correction includes updating the affiliations list to reflect this addition and correct the numbering. The original article has been updated accordingly, and the authors involved in the study are listed in the notice. [Extracted from the article]