Mixed-Methods Study of Disability Self-Management in Mexican Americans With Osteoarthritis.

BACKGROUND: Health disparities in osteoarthritis (OA) outcomes exist both in the occurrence and treatment of functional limitation and disability for Mexican Americans. Although the effect of self-management of chronic illness is well established, studies demonstrate little attention to self-management of function or disability, despite the strong potential effect on both and, consequently, on patients' lives. OBJECTIVE: The purpose of this study pilot was to develop and test key variable relationships for a measure of disability self-management among Mexican Americans. METHODS: In this sequential, two-phased, mixed-methods, biobehavioral pilot study of Mexican American women and men with OA, a culturally tailored measure of disability self-management was created, and initial relationships among key variables were explored. RESULTS: First, a qualitative study of 19 adults of Mexican American descent born in Texas (United States) or Mexico was conducted. The Mexican American Disability Self-Management Scale was created using a descriptive content analysis of interview data. The scale was tested and refined, resulting in 18 items and a descriptive frequency of therapeutic management efforts. Second, correlations between study variables were estimated: Disability and function were negatively correlated. Disability correlated positively with social support and activity effort. Disability correlated negatively with disability self-management, pain, and C-reactive protein. Function was positively correlated with age, pain, and depression. Liver enzymes (alanine transaminase) correlated positively with pain and anxiety. DISCUSSION: This mixed-methods study indicates directions for further testing and interventions for disability outcomes among Mexican Americans.

Epigenetic Aging and Rheumatoid Arthritis.

This is the first known comparative assessment of the associations of epigenetic age estimates with the prevalence of rheumatoid arthritis (RA). We used data available in Gene Expression Omnibus (GSE42861) from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study. Information regarding RA diagnosis and 450K DNA methylation (DNAm) of 18- to 70-year-old participants was available. Utilizing Horvath's online DNAm Age Calculator, we determined the DNAm estimate of Telomere length (DNAmTL), Hannum's epigenetic age, Horvath's 2013 and 2018 epigenetic ages, PhenoAge, GrimAge, and the respective age-acceleration measures. The association of RA prevalence with epigenetic age measures was assessed using linear regression, adjusting for sex and smoking status. The p values were corrected for multiple testing using a false discovery rate. We identified statistically significant associations of RA with Horvath 2013 age acceleration (estimate: -1.34; FDR p value: 1.0 × 10-2), Horvath 2018 age acceleration (estimate: -1.32; FDR p value: 4.0 × 10-5), extrinsic age acceleration (estimate: 1.34; FDR p value: 1.0 × 10-2), PhenoAge acceleration (estimate: 2.31; FDR p value: 1.1 × 10-5), GrimAge (estimate: 2.54; FDR p value: 1.0 × 10-2), and GrimAge acceleration (estimate: 3.15; FDR p-value: 1.7 × 10-17). Of note, the raw and age-adjusted GrimAge surrogate DNAm protein components were significantly higher in RA cases than controls. Interestingly, the first-generation measures were associated only with women. No sex-specific effects were identified for PhenoAge or GrimAge accelerations. In this cross-sectional assessment, the second-generation clocks show promise as markers of biological aging, with higher epigenetic age acceleration observed in RA cases compared with healthy controls.

Targeting allosteric binding site in methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) to identify natural product inhibitors via structure-based computational approach.

Cancer has been viewed as one of the deadliest diseases worldwide. Among various types of cancer, breast cancer is the most common type of cancer in women. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a promising druggable target and is overexpressed in cancerous cells, like, breast cancer. We conducted structure-based modeling on the allosteric site of the enzyme. Targeting the allosteric site avoids the problem of drug resistance. Pharmacophore modeling, molecular docking, HYDE assessment, drug-likeness, ADMET predictions, simulations, and free-energy calculations were performed. The RMSD, RMSF, RoG, SASA, and Hydrogen-bonding studies showed that seven candidates displayed stable behaviour. As per the literature, average superimposed simulated structures revealed a similar protein conformational change in the αE'-ßf' loop, causing its displacement away from the allosteric site. The MM-PBSA showed tight binding of six compounds with the allosteric pocket. The effect of inhibitors interacting in the allosteric site causes a decrease in the binding energy of J49 (active-site inhibitor), suggesting the effect of allosteric binding. The PCA and FEL analysis revealed the significance of the docked compounds in the stable behaviour of the complexes. The outcome can contribute to the development of potential natural products with drug-like properties that can inhibit the MTHFD2 enzyme.

Fucoxanthin levels in maternal serum at birth and eczema risk in offspring in early childhood: A birth cohort study.

BACKGROUND: Fucoxanthin, a marine xanthophyll carotenoid, has been shown to exert beneficial health effects. Cell-based and animal-based experimental studies have shown that fucoxanthin has the potential to mitigate eczema symptoms. Hence, we sought to assess whether fucoxanthinol 3-arachidate, a fucoxanthin metabolite, measured in maternal serum at birth is associated with eczema development during early childhood. METHODS: Data from the 1989/1990 Isle of Wight birth cohort were analyzed. We focused on data obtained from the 1, 2, and 4 years follow-ups. Fucoxanthinol 3-arachidate was measured in maternal serum at the child's birth as abundance relative to the reference lipids. Eczema was ascertained according to parent-reported clinical history and characteristic morphology and distribution. Log-binomial regression models were used to estimate adjusted risk ratios (aRR) and their 95% confidence intervals (CI). RESULTS: A total of 592 subjects (49.2% males and 50.8% females) were included in the current analysis. Associations between fucoxanthinol 3-arachidate levels and eczema risk during the first 4 years of life (longitudinal analysis) were evaluated using four modeling approaches, which showed higher fucoxanthinol 3-arachidate levels were associated with reduced eczema risk: (i) aRRper 10 unit increase = 0.88, 95% CI: 0.76-1.03; (ii) aRR>0 vs. =0 = 0.67, 0.45-0.99; (iii) aRR≥2.3 vs. <2.3 = 0.66, 0.44-0.98; and (iv) aRRtertile 3 vs. tertile 1 = 0.65, 0.42-0.99. CONCLUSION: Our findings suggest that increased fucoxanthinol 3-arachidate levels measured in maternal serum at the child's birth is associated with reduced eczema risk during the first 4 years of the offspring life.

Association of Metabolites, Nutrients, and Toxins in Maternal and Cord Serum with Asthma, IgE, SPT, FeNO, and Lung Function in Offspring.

The role of metabolites, nutrients, and toxins (MNTs) in sera at the end of pregnancy and of their association with offspring respiratory and allergic disorders is underexplored. Untargeted approaches detecting a variety of compounds, known and unknown, are limited. In this cohort study, we first aimed at discovering associations of MNTs in grandmaternal (F0) serum with asthma, immunoglobulin E, skin prick tests, exhaled nitric oxide, and lung function parameters in their parental (F1) offspring. Second, for replication, we tested the identified associations of MNTs with disorders in their grandchildren (F2-offspring) based on F2 cord serum. The statistical analyses were sex-stratified. Using liquid chromatography/high-resolution mass spectrometry in F0, we detected signals for 2286 negative-ion lipids, 59 positive-ion lipids, and 6331 polar MNTs. Nine MNTs (one unknown MNT) discovered in F0-F1 and replicated in F2 showed higher risks of respiratory/allergic outcomes. Twelve MNTs (four unknowns) constituted a potential protection in F1 and F2. We recognized MNTs not yet considered candidates for respiratory/allergic outcomes: a phthalate plasticizer, an antihistamine, a bile acid metabolite, tryptophan metabolites, a hemiterpenoid glycoside, triacylglycerols, hypoxanthine, and polyphenol syringic acid. The findings suggest that MNTs are aspirants for clinical trials to prevent adverse respiratory/allergic outcomes.

An ontology-based approach to designing a NoSQL database for semi-structured and unstructured health data.

With the advent of ICT-based healthcare applications, various formats of health data are generated every day in huge volume. Such data, consisting of unstructured, semi-structured and structured data, has every characteristic of Big data. NoSQL databases are generally preferred for storing such type of health data with the objective of improving query performance. However, for efficient retrieval and processing of Big Health Data and for resource optimization, suitable data models and design of the NoSQL databases are important requirements. Unlike relational databases, no standard methods or tools exist for NoSQL database design. In this work, we adopt an ontology-based schema design approach. We propose that an ontology, which captures the domain knowledge, be used for developing a health data model. An ontology for primary healthcare is described in this paper. We also propose an algorithm for designing the schema of a NoSQL database, keeping in mind the characteristics of the target NoSQL store, using a related ontology, a sample query set, some statistical information of the queries, and performance requirements of the query set. The ontology proposed by us for primary healthcare domain and the above mentioned algorithm along with a set of queries are used for generating a schema targeting MongoDB datastore. The performance of the proposed design is compared with a relational model developed for the same primary healthcare data and the effectiveness of our proposed approach is demonstrated. The entire experiment has been carried out on MongoDB cloud platform.

Analysis and mining of an election-based network using large-scale twitter data: a retrospective study.

The user-generated Twitter data are a rich source of study and research that reflects the various social, economic, political, and other issues affecting people across the world. Analysis of the social interactions among users, who express themselves online, reveals different internal dynamics and provides detailed insights into real-world phenomena. In this paper, the structure and dynamics of the state assembly election-based tweet-reply network have been studied, as generated by Twitter users across the country of India for a period of 6-weeks. We study the flow of Twitter activity pertaining to the West Bengal assembly elections, along with the identification of the hashtags used by the three main political contenders. This information is used to identify the cluster-level dominance in the Twitter network over the 6-weeks of study. It is observed that this cluster dominance information is representative of the actual outcome of the elections, and can be effectively used as a forecasting tool. The collected tweets are used for lexicon-based emotion detection and further analysis. This highlights the reaction of the social media users in response to the events related to the election. It is observed that fear is the dominant emotion, while happiness is scarce in the opinions expressed during the studied duration. Next, the study and analysis of the complete reply-based social networks during weeks 1, 4, and 6 are undertaken. Important political and media actors are identified with standard network-level measures toward determining the efforts put in by the different clusters and individual actors involved in the election to control the network dominance.

Quantum-Controlled Collisions of H2 Molecules.

The amount of information that can be obtained from a scattering experiment depends upon the precision with which the quantum states are defined in the incoming channel. By precisely defining the incoming states and measuring the outgoing states in a scattering experiment, we set up the boundary condition for experimentally solving the Schrödinger equation. In this Perspective we discuss cold inelastic scattering experiments using the most theoretically tractable H2 and its isotopologues as the target. We prepare the target in a precisely defined rovibrational (v, j, m) quantum state using a special coherent optical technique called the Stark-induced adiabatic Raman passage (SARP). v and j represent the quantum numbers of the vibrational and rotational energy levels, and m refers to the projection of the rotational angular momentum vector j on a suitable quantization axis in the laboratory frame. Selection of the m quantum numbers defines the alignment of the molecular frame, which is necessary to probe the anisotropic interactions. For us to achieve the collision temperature in the range of a few degrees Kelvin, we co-expand the colliding partners in a mixed supersonic beam that is collimated to define a direction for the collision velocity. When the bond axis is aligned with respect to a well-defined collision velocity, SARP achieves stereodynamic control at the quantum scale. Through various examples of rotationally inelastic cold scattering experiments, we show how SARP coherently controls the dynamics of anisotropic interactions by preparing quantum superpositions of the orientational m states within a single rovibrational (v, j) energy state. A partial wave analysis, which has been developed for the cold scattering experiments, shows dominance of a resonant orbital that leaves its mark in the scattering angular distribution. These highly controlled cold collision experiments at the single partial wave limit allow the most direct comparison with the results of theoretical computations, necessary for accurate modeling of the molecular interaction potential.

Quantum Controlled Cold Scattering Challenges Theory.

Our previous rotationally inelastic cold scattering experiments between state prepared D2 (v = 2, j = 2, m = 0) and He disagreed with theory, raising serious concerns about either our understanding of the anisotropic potential or the accuracy of the measurement. To further interrogate interactions between molecular hydrogen and atomic helium, we study the Δj = 1and Δj = 2 rotational relaxation of HD (v = 2, j = 2, m = 0) by collision with He. The two rotational transitions probe different anisotropic components of the van der Waals potential. Our state resolved scattering study shows that these two transitions are mediated by two different shape resonances l = 1 for Δj = 1 and l = 2 for Δj = 2. The strong l = 1 resonance dominates the Δj = 1 scattering, agreeing with theory. However, the dominance of the weaker l = 2 resonance in the Δj = 2 transition, which matches our earlier D2-He result, contradicts theoretical calculations. The continued contradiction, when we expect one-to-one correspondence between our stereodynamically controlled scattering experiment and theoretical calculations, makes us question the accuracy of the weaker anisotropic part of the H2-He interaction potential.

Resonant cold scattering of highly vibrationally excited D2 with Ne.

To accurately map weak D2-Ne long-range interactions, we have studied rotationally inelastic cold scattering of D2 prepared in the vibrationally excited (v = 4) and rotationally aligned (j = 2, m) quantum state within the moving frame of a supersonically expanded mixed molecular beam. In contrast to earlier high energy D2-Ne collision experiments, the (j = 2 → j' = 0) cold scattering produced highly symmetric angular distributions that strongly suggest a resonant quasi-bound collision complex that lives long enough to make a few rotations. Our partial wave analysis indicates that the scattering dynamics is dominated by a single resonant l = 2 orbital, even in the presence of a broad temperature (0-5 K) distribution that allows incoming orbitals up to l = 5. The dominance of a single orbital suggests that the resonant complex stabilizes through the coupling of the internal (j = 2) and orbital (l = 2) angular momentum to produce a total angular momentum of J = 0 for the D2-Ne complex.

Coherent Preparation of Highly Vibrating and Rotating D2 Molecules.

Highly vibrationally and rotationally excited hydrogen molecules are of immense interest for understanding and modeling the physics and chemistry of the cold interstellar medium. Using a sequence of two Stark-induced adiabatic Raman passages, we demonstrate the preparation of rotationally excited D2 molecules in the fourth excited vibrational level within its ground electronic state. The nearly complete population transfer to the target state is confirmed by observing both the threshold behavior as a function of the laser power and the depletion of the intermediate level. The vibrational excitation reported here opens new possibilities in the study of the much debated four-center reaction between a pair of hydrogen molecules. Additionally, these rovibrationally excited molecules could be potentially used to generate the high-intensity D- ion beams considered essential for D-T thermonuclear fusion by enhancing the cross section for dissociative electron attachment by 5 orders of magnitude compared to that of the ground state.

Anisotropic dynamics of resonant scattering between a pair of cold aligned diatoms.

The collision dynamics between a pair of aligned molecules in the presence of a partial-wave resonance provide the most sensitive probe of the long-range anisotropic forces important to chemical reactions. Here we control the collision temperature and geometry to probe the dynamics of cold (1-3 K) rotationally inelastic scattering of a pair of optically state-prepared D2 molecules. The collision temperature is manipulated by combining the gating action of laser state preparation and detection with the velocity dispersion of the molecular beam. When the bond axes of both molecules are aligned parallel to the collision velocity, the scattering rate drops by a factor of 3.5 as collision energies >2.1 K are removed, suggesting a geometry-dependent resonance. Partial-wave analysis of the measured angular distribution supports a shape resonance within the centrifugal barrier of the l = 2 incoming orbital. Our experiment illustrates the strong anisotropy of the quadrupole-quadrupole interaction that controls the dynamics of resonant scattering.

Association of prenatal acetaminophen use and acetaminophen metabolites with DNA methylation of newborns: analysis of two consecutive generations of the Isle of Wight birth cohort.

Acetaminophen is used by nearly two-thirds of pregnant women. Although considered safe, studies have demonstrated associations between prenatal acetaminophen use and adverse health outcomes in offspring. Since DNA methylation (DNAm) at birth may act as an early indicator of later health, assessments on whether DNAm of newborns is associated with gestational acetaminophen use or its metabolites are needed. Using data from three consecutive generations of the Isle of Wight cohort (F0-grandmothers, F1-mothers, and F2-offspring) we investigated associations between acetaminophen metabolites in F0 serum at delivery with epigenome-wide DNAm in F1 (Guthrie cards) and between acetaminophen use of F1 and F2-cord-serum levels with F2 cord blood DNAm. In epigenome-wide screening, we eliminated non-informative DNAm sites followed by linear regression of informative sites. Based on repeated pregnancies, indication bias analyses tested whether acetaminophen indicated maternal diseases or has a risk in its own right. Considering that individuals with similar intake process acetaminophen differently, metabolites were clustered to distinguish metabolic exposures. Finally, metabolite clusters from F1-maternal and F2-cord sera were tested for their associations with newborn DNAm (F1 and F2). Twenty-one differential DNAm sites in cord blood were associated with reported maternal acetaminophen intake in the F2 generation. For 11 of these cytosine-phosphate-guanine (CpG) sites, an indication bias was excluded and five were replicated in F2 with metabolite clusters. In addition, metabolite clusters showed associations with 25 CpGs in the F0-F1 discovery analysis, of which five CpGs were replicated in the F2-generation. Our results suggest that prenatal acetaminophen use, measured as metabolites, may influence DNAm in newborns.

Sex-specific developmental trajectories of eczema from infancy to age 26 years: A birth cohort study.

BACKGROUND: Eczema is a common inflammatory skin disease with varying developmental trajectories/patterns that are influenced by different risk factors. The aim of this study was to investigate eczema development from infancy to early adulthood by identifying distinct developmental trajectories that describe disease patterns over time and evaluate the role of prenatal and early-life risk factors. METHODS: The Isle of Wight Birth Cohort (n = 1456) was prospectively assessed at birth, 1, 2, 4, 10, 18 and 26 years. In all assessments, eczema was defined as chronic or chronically relapsing itchy dermatitis lasting >6 weeks with characteristic morphology and distribution in the past 12 months. Developmental trajectories of eczema between 1 or 2 and 26 years were identified separately for males and females by applying semiparametric mixture models. Associations were assessed by applying a modified Poisson regression to estimate adjusted risk ratios (aRR) and 95% confidence intervals (CI). RESULTS: In both males and females, the following eczema developmental trajectories were identified: unaffected/transient (males: 77.7% vs. females: 73.0%), mid-onset late-resolving (males: 7.8% vs. females: 4.4%), late-onset (males: 5.2% vs. females: 9.5%) and early-onset persistent (males: 9.3% vs. females: 5.4%). In females, an additional trajectory was identified as follows: early-onset early-resolving (7.7%). Among males, filaggrin gene (FLG) variants (aRR = 2.45, 95% CI: 1.34-4.46) and paternal eczema (2.66, 1.39-5.08) were associated with the early-onset persistent trajectory. Among females, maternal eczema (2.84, 1.42-5.70) and high birthweight (2.25, 1.08-4.69) were associated with the early-onset persistent trajectory. CONCLUSIONS: Four and five trajectories represented eczema development among males and females, respectively, with different predisposing risk factors. Our results indicate that males and females may experience a different course of eczema.

Quantum mechanical double slit for molecular scattering.

Interference observed in a double-slit experiment most conclusively demonstrates the wave properties of particles. We construct a quantum mechanical double-slit interferometer by rovibrationally exciting molecular deuterium (D2) in a biaxial (v = 2, j = 2) state using Stark-induced adiabatic Raman passage, where v and j represent the vibrational and rotational quantum numbers, respectively. In D2 (v = 2, j = 2) → D2 (v = 2, j' = 0) rotational relaxation via a cold collision with ground state helium, the two coherently coupled bond axis orientations in the biaxial state act as two slits that generate two indistinguishable quantum mechanical pathways connecting initial and final states of the colliding system. The interference disappears when we decouple the two orientations of the bond axis by separately constructing the uniaxial states of D2, unequivocally establishing the double-slit action of the biaxial state. This double slit opens new possibilities in the coherent control of molecular collisions.

Association of grandmaternal smoking during pregnancy with DNA methylation of grandchildren: the Isle of Wight study.

Background: To investigate the intergenerational effects of grandmaternal smoking during pregnancy (GMSDP) on the DNA methylation of grandchildren. Methods: Data from the Isle of Wight birth cohort with information regarding GMSDP and DNA methylation profiling at the birth of grandchildren (n = 161) were used. Differentially methylated CpG sites related to GMSDP were identified using testing-training screening, analysis of variance and multivariate analysis of covariance. The association between identified CpG sites and expression levels of neighboring genes was tested by linear regression. Results: Twenty-three CpG sites were differentially methylated in grandchildren because of GMSDP, and eight of these were associated with expression levels of 13 neighboring genes. Conclusion: GMSDP has an intergenerational effect on the DNA methylation profile of grandchildren independent of maternal smoking during pregnancy.

Lay abstract This study aimed to assess how grandmaternal smoking during pregnancy can affect the health of grandchildren. Underlying mechanisms may include epigenetic modifications. To address this topic, the authors investigated the intergenerational effects of grandmaternal smoking during pregnancy on the DNA methylation of grandchildren at birth based on the Isle of Wight birth Cohort. Twenty-three CpG sites were differentially methylated in grandchildren because of grandmaternal smoking during pregnancy, and eight of these were associated with changes in expression levels of 13 neighboring genes. Thus, grandmaternal smoking during pregnancy has an intergenerational effect on the DNA methylation profile of grandchildren independent of maternal smoking during pregnancy.

Shape resonance determined from angular distribution in D2 (v = 2, j = 2) + He → D2 (v = 2, j = 0) + He cold scattering.

We find an l = 2 shape resonance fingerprinted in the angular distribution of the cold (∼1 K) Δj = 2 rotationally inelastic collision of D2 with He in a single supersonic expansion. The Stark-induced adiabatic Raman passage is used to prepare D2 in the (v = 2, j = 2) rovibrational level with control of the spatial distribution of the bond axis of the molecule by magnetic sublevel selection. We show that the rate of Δj = 2 D2-D2 relaxation is nearly two orders of magnitude weaker than that of D2-He. This suggests that the strong D2-He scattering is caused by an orbiting resonance that is highly sensitive to the shape of the long-range potential.

Association of Maternal DNA Methylation and Offspring Birthweight.

This study aims to evaluate the association of maternal DNA methylation (DNAm) during pregnancy and offspring birthweight. One hundred twenty-two newborn-mother dyads from the Isle of Wight (IOW) cohort were studied to identify differentially methylated cytosine-phosphate-guanine sites (CpGs) in maternal blood associated with offspring birthweight. Peripheral blood samples were drawn from mothers at 22-38 weeks of pregnancy for epigenome-wide DNAm assessment using the Illumina Infinium HumanMethylation450K array. Candidate CpGs were identified using a course of 100 repetitions of a training and testing process with robust regressions. CpGs were considered informative if they showed statistical significance in at least 80% of training and testing samples. Linear mixed models adjusting for covariates were applied to further assess the selected CpGs. The Swedish Born Into Life cohort was used to replicate our findings (n = 33). Eight candidate CpGs corresponding to the genes LMF1, KIF9, KLHL18, DAB1, VAX2, CD207, SCT, SCYL2, DEPDC4, NECAP1, and SFRS3 in mothers were identified as statistically significantly associated with their children's birthweight in the IOW cohort and confirmed by linear mixed models after adjusting for covariates. Of these, in the replication cohort, three CpGs (cg01816814, cg23153661, and cg17722033 with p values = 0.06, 0.175, and 0.166, respectively) associated with four genes (LMF1, VAX2, CD207, and NECAP1) were marginally significant. Biological pathway analyses of three of the genes revealed cellular processes such as endocytosis (possibly sustaining an adequate maternal-fetal interface) and metabolic processes such as regulation of lipoprotein lipase activity (involved in providing substrates for the developing fetus). Our results contribute to an epigenetic understanding of maternal involvement in offspring birthweight. Measuring DNAm levels of maternal CpGs may in the future serve as a diagnostic tool recognizing mothers at risk for pregnancies ending with altered birthweights.

DNA methylation at birth is associated with lung function development until age 26†years.

Little is known about whether DNA methylation (DNAm) of cytosine-phosphate-guanine (CpG) sites at birth predicts patterns of lung function development. We used heel prick DNAm from the F1-generation of Isle of Wight birth cohort (IOWBC-F1) for discovery of CpGs associated with lung function trajectories (forced expiratory volume in 1 s, forced vital capacity, their ratio, and forced expiratory flow at 25-75% of forced vital capacity) over the first 26 years, stratified by sex. We replicated the findings in the Avon Longitudinal Study of Parents and Children (ALSPAC) using cord blood DNAm.Epigenome-wide screening was applied to identify CpGs associated with lung function trajectories in 396 boys and 390 girls of IOWBC-F1. Replication in ALSPAC focussed on lung function at ages 8, 15 and 24 years. Statistically significantly replicated CpGs were investigated for consistency in direction of association between cohorts, stability of DNAm over time in IOWBC-F1, relevant biological processes and for association with gene expression (n=161) in IOWBC F2-generation (IOWBC-F2).Differential DNAm of eight CpGs on genes GLUL, MYCN, HLX, LHX1, COBL, COL18A1, STRA6, and WNT11 involved in developmental processes, were significantly associated with lung function in the same direction in IOWBC-F1 and ALSPAC, and showed stable patterns at birth, aged 10 and 18 years between high and low lung function trajectories in IOWBC-F1. CpGs on LHX1 and COL18A1 were linked to gene expression in IOWBC-F2.In two large cohorts, novel DNAm at birth were associated with patterns of lung function in adolescence and early adulthood providing possible targets for preventative interventions against adverse pulmonary function development.