Background and Aims To elucidate the genetic architecture of blood pressure (BP) and heart rate (HR) during early life and assess their potential relevance to adult health outcomes.Methods The largest genome-wide association study (GWAS) meta-analyses to date of childhood systolic BP, diastolic BP, pulse pressure, and mean arterial pressure (n = 28 425) and HR (n = 22 565) were conducted in children of European ancestry aged 4-17 years. Follow-up analyses included comparisons with adult GWAS results, polygenic risk score (PRS) analyses in independent cohorts of diverse ancestries, and a phenome-wide association study in the UK Biobank.Results Eight genome-wide significant loci were identified for childhood BP (KIAA2013, CACNB2, PLCE1, PAX2, COL4A2, RP11-236L14.1, CFDP1, TPX2) and three loci for childhood HR (CCDC141, ACHE, MYH6); all novel in children but previously reported in adults. Childhood PRSs explained up to 1.6% of BP variance and 5.2% of HR variance among children of European ancestry. Genetic correlations between childhood and adulthood BP traits were moderate (rg = 0.4-0.7), suggesting age-specific genetic effects on BP. In the UK Biobank, higher childhood BP PRS levels were significantly associated with a broad range of adult health outcomes, particularly cardiometabolic outcomes such as hypertension, angina, myocardial infarction, and cardiovascular disease-related mortality.Conclusions These findings advance the understanding of the genetic architecture of childhood BP and HR and provide compelling genetic evidence linking childhood BP to a broad spectrum of adult health outcomes-particularly cardiometabolic conditions-which may inform targeted prevention strategies from a young age.

This paper presents the HL7 FHIR-based interoperability architecture developed within the STAGE Project to enable the seamless integration of personalised decision support, health monitoring, and health coaching applications for the prevention and management of ageing with multi-morbidity. The architecture leverages international standards, including CDS Hooks, SMART on FHIR, and the International Patient Summary (IPS), to support vendor-agnostic data exchange and scalable deployment across healthcare settings.

Wellbeing is associated with both behavioral phenotypes as well as several key life outcomes, such as health, employment, and coping with stressful events. These phenotypes associated with wellbeing could be potential indicators of differential epigenetic patterns between individuals that differ in their levels of wellbeing. We performed the largest epigenome-wide (EWAS) meta-analysis of wellbeing to date by combining whole blood DNA methylation data (Illumina 450K array) from 13 cohorts from Europe, Australia, and the USA (N = 10,757 participants). After correcting for smoking and BMI, no epigenome-wide significant methylation sites were identified. We tested whether a weighted methylation score (MS) based on leave-one-cohort-out EWAS meta-analysis summary statistics predicted wellbeing in an independent cohort, and whether prediction was significant over and above the polygenic score (PGS) for wellbeing. The MS was associated with wellbeing (variance explained = 0.22

Digital health technologies offer promising opportunities for longitudinal health monitoring, yet their adoption in research settings faces significant barriers including usability concerns, participant burden, and data privacy issues. This paper presents the design, implementation, and usability evaluation of a person-centered digital health system for scalable, privacy-preserving longitudinal health monitoring in ageing populations. The system was developed within the STAGE project to support a two-year study (2026–2028) with approximately 10,000 participants from the Northern Finland Birth Cohort (NFBC1966). The system employs a modular, privacy-centered architecture comprising a cross-platform mobile application and a cloud backend infrastructure, all designed to be GDPR-compliant with comprehensive security measures. Development was guided by structured co-creation activities and patient and public involvement (PPI) through interviews, questionnaires, and workshops with diverse stakeholders including ageing citizens, caregivers, clinicians, and researchers. The mobile application enables periodic self-reported assessments of wellbeing, cognitive and physical functioning, mental health, nutrition, anthropometric measurements, falls, and mobility patterns, complemented by GPS-based mobility tracking during four-week monitoring periods. The system employs a foreground-first data collection approach requiring explicit user interaction to maintain transparency and trust. Two pilot studies demonstrated strong usability outcomes. Pilot #1 (N = 11) yielded high Single Ease Question scores (all means > 5.6/7). Pilot #2 (N = 17) achieved a System Usability Scale score of 87.95 (SD = 8.18), classified as “Excellent,” with no critical issues reported. The platform includes FHIR-compliant data export capabilities (17 profiles, 12 valuesets) to facilitate healthcare system integration. While challenges remain regarding long-term engagement and digital literacy variability, the system provides a robust foundation for sustainable, participant-centered longitudinal health research in ageing populations.

Objective: To test the association between preterm-birth and time to occurrence of a subsequent pregnancy, compared with term-birth. Design: Prospective cohort study using health and demographic surveillance system data. Setting: Matlab area, Bangladesh (1990-2020). Population or Sample: 52,502 pregnancies from 24,559 women, excluding pregnancies with multiple fetuses and women whose first pregnancy occurred after 45 years of age. Methods: Main exposure was preterm-birth. Previous miscarriages and stillbirths served as secondary exposures. Associations were assessed using recurrent survival analysis.. Impact of infant mortality was assessed by including death of the previous child under one year of age as time-dependent variable. Hazard ratio (HR) of a subsequent pregnancy was calculated with 95% confidence intervals (CIs). Main Outcome Measures: time to occurrence of a subsequent pregnancy counted as the date of the previous event until the date of the next last menstrual period. Results: Women with a previous extremely-very and moderately preterm-birth had an increased likelihood for subsequent pregnancy, compared to women with a term-birth (Adj.HR: 1.22 (95% CI 1.08-1.39; 1.13 (1.04-1.23), respectively). After adjusting for death of the previous child HRs reduced to 0.97 (0.85-1.09) and 1.03 (0.95-1.12), suggesting that the increased HRs observed was explained by infant death. Previous stillbirth and miscarriage were associated with approximately three-fold likelihood of a subsequent pregnancy. Conclusions: In Matlab, women with a previous preterm-birth were more likely to get pregnant than women with a previous term-birth. However, after adjusting for infant mortality there was no difference in pregnancy rates between previous preterm or term-birth.

Climate exposures have been associated with cardiovascular health, but most studies focus on short-term exposure and individual climate parameters. This study explored the use of longitudinal multidimensional clustering in studying climate exposures over the life-course, in relation to adult blood pressure (BP). Annual averages of seven climate exposures were linked to the residential coordinates of the Northern Finland Birth Cohort 1966 (n = 4,225). Individual climate trajectories were grouped by a non-parametric algorithm for clustering joint trajectories (kml3d) across youth (4-24y) and adulthood (25-46y). Generalized linear models were used to assess the relationship between climate clusters and clinically measured systolic BP (SBP) and diastolic BP (DBP) at 46 years, adjusting for relevant confounders. Two youth clusters (A and B) were identified, while three clusters (A, B and C) emerged in adulthood. Compared to cluster A, the reference at both stages, B describes a colder northern climate, while C represents a transition to a warmer southern climate. Results show that growing up in the coldest climate (B) was associated with lower SBP (-1.13 mmHg, 95%CI -2.21, -0.05). Adult exposure to the warmest southern climate (C) was associated with lower SBP (-4.17 mmHg, 95%CI -5.38, -2.97) and DBP (-1.90 mmHg, 95%CI -2.72, -1.08). Youth and adult climate exposures were independently associated with adult BP. Future studies should assess to which extent health inequality plays a role. Our results show that kml3d clustering can identify distinct regional climates, facilitating observational studies on climate exposure.

Background Cardiovascular disease is socioeconomically patterned, and risk accrues from early life. Evidence in younger populations is scarce. We investigated the extent to which early life socioeconomic position is associated with cardiovascular health in children and adolescents, and the extent of mediation by body mass index. Methods We analyzed 5 longitudinal birth cohorts: BIS (the Barwon Infant Study; Australia; mean age 4.1 years; n=708); BiB (Born in Bradford; United Kingdom; mean age 9.3 years; n=4576); LSAC‐CP (the Longitudinal Study of Australian Children's Child Health CheckPoint; Australia; mean age 12.0 years; n=1874); NFBC1986 (the Northern Finland Birth Cohort 1986; Finland; mean age 16.0 years; n=9467); and ALSPAC (the Avon Longitudinal Study of Parents and Children; United Kingdom; mean age 17.8 years; n=4875). Exposures were neighborhood disadvantage, household socioeconomic position, and maternal education (in pregnancy/at birth). Outcomes were carotid intima‐media thickness, pulse‐wave velocity, blood pressure, and lipids (in childhood/adolescence). Results From age 12 years, children with lower socioeconomic position had worse cardiovascular health, adjusted for age, sex, and ethnicity. For example, LSAC‐CP 12‐year‐olds in the most disadvantaged neighborhoods had higher pulse‐wave velocity (β=0.1 m/s [95% CI, 0.03–0.2 m/s]; P=0.003) than those in the most advantaged, and NFBC1986 16‐year‐olds whose mothers had the lowest education levels had higher triglycerides (β=0.07 mmol/L [95% CI, 0.0–0.1 mmol/L]; P=0.04) than those whose mothers had the highest education levels. Hypothetically intervening on body mass index would reduce 12% to 100% of some cardiovascular health differences. Conclusions Associations between lower socioeconomic position and worse cardiovascular health are apparent from midchildhood. Prevention efforts should address intermediate mechanisms and upstream neighborhood, household, and maternal factors.

Objectives There is evidence to suggest that alterations in skin health often co-occur with type 2 diabetes (T2D). However, the underlying mechanisms remain unclear. Despite their clinical relevance, skin conditions are often underdiagnosed in diabetes care. This study applied variable selection methods to identify key dermatological factors linked to T2D and examined their direct and indirect associations.Design Prospective birth cohort study.Participants This study analysed data from the Northern Finland Birth Cohort 1966, including 1906 participants (1024 women, 882 men) at ages 31 and 46 years. At age 46 years, the cohort participants, living in the region of Northern Finland, were invited to a general health clinical examination including the assessment of their T2D status and a dermatological examination.Methods Prior to performing a path analysis, we developed a data-driven procedure to select 47 possible skin-related variables for the model. The variable selection combined test-based methods (ie, a univariate analysis and a backward, forward and stepwise logistic regression) and penalty-based/machine learning methods (ie, Least Absolute Shrinkage and Selection Operator, Ridge, minimax convex penalty and Sparse Stepwise Regression). The selected skin-related variables were then included in a path analysis accounting for sex, body mass index (BMI), diet, education, depression, anxiety and sleep quality.Results Eight skin-related variables were selected and included in the path analysis. Psoriasis (OR 1.105, 95% CI 1.058 to 1.156) and Tinea pedis (OR 1.067, 95% CI 1.04 to 1.096) showed direct associations with T2D. Hyperhidrosis (OR 1.017, 95% CI 1.005 to 1.037) exhibited an indirect effect.Conclusions These results underscored the interconnectedness of dermatological conditions such as psoriasis and Tinea pedis with T2D. These findings suggest that certain skin conditions may serve as potential indicators of T2D. Early recognition and appropriate management of these conditions may help improve patients’ quality of life.

Biological ageing begins before birth, with early-life exposures shaping late-life health. These exposures drive health inequities early, yet specific exposures and the composition of the ageing exposome remain largely undefined. This gap may persist as the field lacks agnostic investigations accounting for non-linearity, interactions and subtle signals. We aimed to identify exposures predictive of epigenetic ageing accumulated during childhood and adolescence and explore the composition of the "missing" exposome. In the FinnTwin12 cohort (847 participants measured at ages 12, 14, 17, and 22), 186 unique exposures (including lifestyle, green environments, air pollutants, and demographic factors) were analysed using exposome-wide association studies and data-driven ML models (Knockoff Boosted Tree, sNPLS and Boruta). Epigenetic age (blood DNA methylation at age 22) was estimated using PCGrimAge and DunedinPACE. Our exposure set explains ∼ 28% of the variance in epigenetic age (R2PCGrimAge = 25.7%; R2DunedinPACE = 30.8%). Predictors of increased epigenetic age included lifestyle and socioeconomic factors (smoking, alcohol use, youth unemployment), alongside size of green space, while tree cover, vegetation index, neighbourhood age structure and aerial black carbon emerged as predictors of decreased epigenetic age. Twin modelling revealed that unexplained variance - the 'missing exposome' - consists primarily of environmental factors unshared by twin siblings, distinct from the substantial genetic component captured by our model. Our results underscore the need to expand the exposome approach and model non-linearities to reveal subtle environmental signals accumulating early in life. Because identified predictors include modifiable systemic factors, they offer opportunities to alter health trajectories and mitigate inequity early on.

Chronic inflammation may be a key mechanism driving social to biological transitions across the lifecourse. We investigated the effect of early-life socioeconomic position (SEP) on inflammatory biomarkers in childhood and adolescence and assessed mediation by body mass index (BMI). We conducted cohort-specific analysis in five birth cohorts: the Barwon Infant Study (BIS, Australia, n = 708, 4-5 years); Born in Bradford (BiB, United Kingdom, n = 4576, 7-11 years); the Longitudinal Study of Australian Children's Child Health CheckPoint (LSAC-CP, Australia, n = 1874, 11-12 years); the Northern Finland Birth Cohort 1986 (NFBC1986, Finland, n = 9467, 15-16 years); and the Avon Longitudinal Study of Parents and Children (ALSPAC, United Kingdom, n = 4875, 17-18 years). Exposures were neighbourhood disadvantage, household economic conditions, and maternal education, in pregnancy or infancy. Outcomes were log-transformed high sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls (GlycA) levels. We conducted confounder-adjusted linear regression to estimate the effect of exposures on outcomes, and mediation analysis using interventional effects to assess mediation by BMI. Lower early-life SEP, particularly neighbourhood disadvantage and lower maternal education, was associated with higher inflammation from the age of 7-11 years. Effects were most apparent for GlycA (e.g., mean GlycA difference between BiB children in most and least disadvantaged neighbourhoods: 0.1 SD [95% CI 0.03-0.2]; between NFBC1986 adolescents with most and least educated mothers: 0.2 SD [0.02, 0.3]). BMI partially mediated many of these effects (20-100%). Neighbourhood disadvantage and lower maternal education may increase inflammation in children and adolescents, in part through higher adiposity. This underscores the importance of addressing socioeconomic conditions in early life and of preventing excess BMI.

BACKGROUND:Traffic noise has been associated with the risk of cardiometabolic diseases. Identifying internal exposome factors, such as metabolomic biomarkers, associated with traffic noise in the general population may help clarify the pathophysiological pathways linking noise to cardiometabolic outcomes. To address this gap, we investigated the relationships between nighttime road traffic noise and systemic metabolic biomarkers. METHODS:This study included 272,229 European adults, aged 31 years and over, from the UK Biobank (UKBB), the Rotterdam Study (RS), and the Northern Finland Birth Cohort 1966 (NFBC1966). Annual average nighttime road traffic noise was linked to the individual residential address at the time of blood sampling, using national noise maps. We utilized high-throughput nuclear magnetic resonance metabolomics to profile 155 biomarkers (including lipids, lipoproteins, fatty acids, and other low-molecular-weight metabolites). In discovery analyses in UKBB, we applied linear models adjusted for age, sex, education, and fine particulate matter to identify significant biomarkers (Bonferroni P < 0.003125). The associated biomarkers were further assessed using multilevel random-effects meta-analysis across the UKBB, RS, and NFBC1966. RESULTS:From the discovery analysis, nighttime road traffic noise (≥55 dB versus <45 dB) was associated with higher levels of 48 metabolites in the UKBB. Associations for 20 metabolites remained robust in meta-analysis and through sensitivity analyses. Noise (≥55 dB) was associated with elevated circulating concentrations of cholesterol-related biomarkers, including lipids in esterified cholesterol-enriched lipoproteins such as low-density lipoprotein (LDL) and intermediate-density lipoprotein (IDL), as well as unsaturated fatty acids and membrane biomarkers. Except for two unsaturated fatty acids, these biomarkers showed a monotonic exposure-response pattern from 50 dB onward. CONCLUSION:This study provides evidence that nighttime road traffic noise exposure from 50 dB upward is associated with alterations in blood cholesterol and lipid profiles in adults. This finding may clarify the association between traffic noise and cardiometabolic diseases.

[This corrects the article DOI: 10.1371/journal.pmen.0000334.].

Gestational diabetes mellitus (GDM) affects ~14% of pregnancies and increases maternal type 2 diabetes mellitus (T2DM) risk. The GenDiP Consortium presents trans-generational, multi-ancestry genome-wide association study meta-analyses of GDM and pregnancy glycemic traits in up to 38,305 GDM cases and 776,145 controls. We identify 37 GDM-associated loci (7 novel) and five novel loci for pregnancy glycemic traits, all operating through the maternal genome. We classify 12 GDM variants with stronger effects in GDM than T2DM into five biologically informed categories, revealing pleiotropy patterns, pregnancy-dependent effect modification, and diagnostic heterogeneity. While all these loci overlap with T2DM and/or non-pregnant glycaemic traits, four (G6PC2, CAST-PCSK1, HKDC1, FOXA2) lack genome-wide-significant T2DM associations; GCK shows distinct causal variants for GDM, and MTNR1B exhibits pregnancy-amplified effects. Our findings provide new genetic insights into GDM and highlight the need for larger, ancestrally diverse studies of GDM and glycaemic traits during pregnancy to understand potential pregnancy-specific effects.

Background: Cardiovascular disease (CVD) is socioeconomically patterned and risk accrues from early life. Evidence in younger populations is scarce. We investigated the extent to which early life socioeconomic position (SEP) affects cardiovascular health (CVH) in children and adolescents, and the extent of mediation by body mass index (BMI). Methods and Results: We analysed 5 longitudinal cohorts: the Barwon Infant Study (BIS, Australia, mean age 4.1 years, n=708); Born in Bradford (United Kingdom, mean age 9.3 years, n=4576); the Longitudinal Study of Australian Children?s Child Health CheckPoint (LSAC-CP, Australia, mean 12.0 years, n=1874); the Northern Finland Birth Cohort 1986 (NFBC1986) (Finland, mean 16.0 years, n=9467); and the Avon Longitudinal Study of Parents and Children (ALSPAC, United Kingdom, mean 17.8 years, n=4875). Exposures were neighborhood disadvantage, household SEP, and maternal education (in pregnancy/at birth). Outcomes were carotid intima-media thickness, pulse wave velocity, blood pressure, and lipids (in childhood/adolescence). From 12 years, those with lower SEP had worse CVH, adjusted for age, sex, and ethnicity. For example, LSAC-CP 12-year-olds in the most disadvantaged neighborhoods had higher pulse wave velocity (??=?0.1 m/s; 95% CI, 0.03-0.2; P=0.003) than those in the most advantaged, and NFBC1986 16-year-olds whose mothers had the lowest education had higher triglycerides (??= 0.07 mmol/L; 95% CI, 0.0-0.1; P=0.04) than those whose mothers had the highest education. Hypothetical reductions in CVH differences by shifting BMI distributions varied by cohort and exposure. Conclusions: The adverse effects of lower SEP on CVH are apparent from mid-childhood. Prevention should address intermediate mechanisms and upstream neighborhood, household, and maternal factors. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by a University of Melbourne Graduate Research Scholarship. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Human Research and Ethics Committee (reference: 10/24) of Barwon Health gave ethical approval for the Barwon Infant Study. The Health Research Authority Yorkshire and the Humber (Bradford Leeds) Research Ethics Committee (reference: 16/YH/0320) of the National Health Service United Kingdom gave ethical approval for Born in Bradford. The Human Research Ethics Committee of the Royal Children's Hospital Melbourne (reference: 33225D) and the Ethics Committee of the Australian Institute of Family Studies (reference: 14-26) gave ethical approval for the Longitudinal Study of Australian Children's Child Health CheckPoint. The Ethical Committee of the Northern Ostrobothnia Hospital District (reference: 108/2017) gave ethical approval for the Northern Finland Birth Cohort 1986. The Ethics and Law Committee of the Avon Longitudinal Study of Parents and Children and the Research Ethics Committees of the Bristol and Weston Health Authority (reference: E1808), Southmead Health Authority (reference: 49/89), Frenchay Health Authority (reference: 90/8), and the North Somerset & South Bristol Authority (reference: 08/H0106/9), gave ethical approval for the Avon Longitudinal Study of Parents and Children. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Barwon Infant Study (BIS) data are available under restricted access on scientific and ethical grounds by the BIS Steering Committee and provided through a collaborative research agreement. A description of the available data is available on the cohort website: https://barwoninfantstudy.org.au. Born in Bradford (BiB) data are available under restricted access through application on the study website, where information on the available data is also available: https://borninbradford.nhs.uk/research/how-to-access-data/. Data from the Longitudinal Study of Australian Children's Child Health CheckPoint (LSAC-CP) are available under restricted access and may be obtained by request through the Australian Data Archive (https://ada.edu.au/) for researchers in Australia affiliated with an approved research body. Northern Finland Birth Cohort 1986 (NFBC1986) data are available under restricted access through application on the study website (https://www.oulu.fi/en/university/facultiesand- units/faculty-medicine/northern-finland-birth-cohorts-and-arctic-biobank/nfbcaineistopyynto) and provided through a collaborative research agreement with the University of Oulu. The informed consent obtained from ALSPAC (Avon Longitudinal Study of Parents and Children) participants does not allow the data to be made available through any third party maintained public repository. Supporting data are available from ALSPAC on request under the approved proposal number, B4806. Full instructions for applying for data access can be found here: http://www.bristol.ac.uk/alspac/researchers/access/. The ALSPAC study website contains details of all available data, including a data dictionary and variable search tool (http://www.bristol.ac.uk/alspac/researchers/our-data/).

DNA methylation (DNAm) is a developmentally dynamic epigenetic process; yet, most epigenome-wide association studies (EWAS) have examined DNAm at only one timepoint or without systematic comparisons between timepoints. Thus, it is unclear whether DNAm alterations during certain developmental periods are more informative than others for health outcomes, how persistent epigenetic signals are across time, and whether epigenetic timing effects differ by outcome. We applied longitudinal meta-regression models to published meta-analyses from the PACE consortium that examined DNAm at two timepoints—prospectively at birth and cross-sectionally in childhood—in relation to the same child outcome (ADHD symptoms, general psychopathology, sleep duration, BMI, asthma). These models allowed systematic comparisons of effect sizes and statistical significance between timepoints. Furthermore, we tested correlations between DNAm regression coefficients to assess the consistency of epigenetic signals across time and outcomes. Finally, we performed robustness checks, estimated between-study heterogeneity, and tested pathway enrichment. Our findings reveal three new insights: (i) across outcomes, DNAm effect sizes are consistently larger in childhood cross-sectional analyses compared to prospective analyses at birth; (ii) higher effect sizes do not necessarily translate into more significant findings, as associations also become noisier in childhood for most outcomes (showing larger standard errors in cross-sectional vs prospective analyses); and (iii) DNAm signals are highly time-specific, while also showing evidence of shared associations across health outcomes (ADHD symptoms, general psychopathology, and asthma). Notably, these observations could not be explained by sample size differences and only partly to differential study-heterogeneity. DNAm sites changing associations were enriched for neural pathways. Our results highlight developmentally-specific associations between DNAm and child health outcomes, when assessing DNAm at birth vs childhood. This implies that EWAS results from one timepoint are unlikely to generalize to another. Longitudinal studies with repeated epigenetic assessments are direly needed to shed light on the dynamic relationship between DNAm, development and health, as well as to enable the creation of more reliable and generalizable epigenetic biomarkers. More broadly, this study underscores the importance of considering the time-varying nature of DNAm in epigenetic research and supports the potential existence of epigenetic “timing effects” on child health.

Children’s biological age does not always correspond to their chronological age. In the case of BMI trajectories, this can appear as phase variation, which can be seen as shift, stretch, or shrinking between trajectories. With maturation thought of as a process moving towards the final state - adult BMI, we assessed whether children can be divided into latent groups reflecting similar maturational age of BMI. The groups were characterised by early factors and time-related features of the trajectories. We used data from two general population birth cohort studies, Northern Finland Birth Cohorts 1966 and 1986 (NFBC1966 and NFBC1986). Height (n = 6329) and weight (n = 6568) measurements were interpolated in 34 shared time points using B-splines, and BMI values were calculated between 3 months to 16 years. Pairwise phase distances of 2999 females and 3163 males were used as a similarity measure in k-medoids clustering. We identified three clusters of trajectories in females and males (Type 1: females, n = 1566, males, n = 1669; Type 2: females, n = 1028, males, n = 973; Type 3: females, n = 405, males, n = 521). Similar distinct timing patterns were identified in males and females. The clusters did not differ by sex, or early growth determinants studied. Trajectory cluster Type 1 reflected to the shape of what is typically illustrated as the childhood BMI trajectory in literature. However, the other two have not been identified previously. Type 2 pattern was more common in the NFBC1966 suggesting a generational shift in BMI maturational patterns.

Air pollution, noise, and built environment are associated with the epidemics of type 2 diabetes (T2D). The extent to which these have independent and/or joint effects on T2D and whether some components of the urban exposome have stronger effects remains unclear. We conducted a systematic review of the associations of 11 environmental exposures of urban exposome with the risk of T2D. We searched PubMed and Scopus since 2005 until January 2025 for studies on association of T2D in adults with air pollution; particles with a diameter of less than 2.5 (PM2.5) and 10 µm (PM10), nitrogen dioxide (NO2), ozone (O3) and black carbon (BC), noise; traffic-, railway-, and aircraft noise, and built environment; greenness, walkability, and population density. We included 151 articles, one study referring to exposome approach. Air pollutants were associated with T2D risk in meta-analyses, BC showing strongest association, OR: 1.32, 95% CI: 1.15-1.50 (n = 8). Subgroup analyses and meta-regression for PM2.5, PM10, NO2, and O3 by study characteristics highlighted variations in risk estimates but didn’t explain considerable heterogeneity. Traffic noise was associated with T2D (OR: 1.06, 95% CI: 1.03, 1.08, n = 11). In qualitative synthesis, living environment with higher walkability and greenness showed inverse association with T2D. Results indicate that air pollution and traffic noise are associated with increased risk of T2D. Greener and walkable living environment can potentially reduce risk of T2D. It remained unclear whether the effects were independent. Future studies should consider environmental joint exposures. Advancing use of exposome approach can help understand T2D risk comprehensively.

Non-coding 886 (nc886, vtRNA2-1) is a polymorphically imprinted gene. The methylation status of this locus has been shown to be associated with periconceptional conditions, and both the methylation status and the levels of nc886 RNAs have been shown to associate with later-life health traits. We have previously shown that nc886 RNA levels are associated not only with the methylation status of the locus, but also with a genetic polymorphism upstream from the locus. In this study, we describe the genetic and epigenetic regulators that predict lifelong nc886 RNA levels, as well as their association with cardiometabolic disease (CMD) risk factors and events. We utilised six population cohorts and one CMD cohort comprising 9058 individuals in total. The association of nc886 RNA levels, as predicted by epigenetic and genetic regulators, with CMD phenotypes was analysed using regression models, with a meta-analysis of the results. The meta-analysis showed that individuals with upregulated nc886 RNA levels have higher diastolic blood pressure (β = 0.07, p = 0.008), lower HDL levels (β = − 0.07, p = 0.006) and an increased incidence of type 2 diabetes (OR = 1.260, p = 0.013). Moreover, CMD patients with upregulated nc886 RNA levels have an increased incidence of stroke (OR = 1.581, p = 0.006) and death (OR = 1.290, p = 0.046). In conclusion, we show that individuals who are predicted to present elevated nc886 RNA levels have poorer cardiovascular health and are at an elevated risk of complications in secondary prevention. This unique mechanism yields metabolic variation in human populations, constituting a CMD risk factor that cannot be modified through lifestyle choices.