We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.

Obesity is associated with inflammation but the role of vitamin D in this process is not clear. We aimed to assess the associations between serum 25-hydroxyvitamin D [25(OH)D], BMI, and 16 inflammatory biomarkers, and to assess the role of vitamin D as a potential mediator in the association between higher BMI and inflammation. Northern Finland Birth Cohort 1966 (NFBC1966) 31-y data on 3586 individuals were analyzed to examine the observational associations between BMI, 25(OH)D, and 16 inflammatory biomarkers. Multivariable regression analyses and 2-sample regression-based Mendelian randomization (MR) mediation analysis were performed to assess any role of vitamin D in mediating a causal effect of BMI on inflammatory biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1), high sensitivity C-reactive protein (hs-CRP), and α1-acid glycoprotein (AGP)] for which observational associations were detected. For MR, genome-wide association study summary results ranging from 5163 to 806,834 individuals were used for biomarkers, 25(OH)D, and BMI. Findings were triangulated with a literature review of vitamin D supplementation trials. In NFBC1966, mean BMI (kg/m²) was 24.8 (95% CI: 24.7, 25.0) and mean 25(OH)D was 50.3 nmol/L (95% CI: 49.8, 50.7 nmol/L). Inflammatory biomarkers correlated as 4 independent clusters: interleukins, adhesion molecules, acute-phase proteins, and chemokines. BMI was positively associated with 9 inflammatory biomarkers and inversely with 25(OH)D (false discovery rate < 0.05). 25(OH)D was inversely associated with sICAM-1, hs-CRP, and AGP, which were positively associated with BMI. The MR analyses showed causal association of BMI on these 3 inflammatory biomarkers. There was no observational or MR evidence that circulating 25(OH)D concentrations mediated the association between BMI and these 3 inflammatory markers. Review of randomized controlled trials (RCTs) supported our findings showing no impact of vitamin D supplementation on inflammatory biomarkers. The findings from our observational study and causal MR analyses, together with data from RCTs, do not support a beneficial role of vitamin D supplementation on obesity-related inflammation.

We explored whether registered unemployment is associated with impaired glucose metabolism in general population. Based on Northern Finland Birth Cohort 1966 at 46 years, we analyzed the oral glucose tolerance tests of 1970 men and 2544 women in relation to their preceding three-year employment records in three categories of unemployment exposure: no (employed), low (≤1-year) and high exposure (>1-year). Among men, pre-diabetes was found in 19.2% of those with no unemployment, 23.0% with low and 27.0% with high exposure, the corresponding figures for screen-detected type 2 diabetes were 3.8%, 3.8% and 9.2% (p<0.01). Among women, analogous figures for pre-diabetes were 10.0%, 12.6% and 16.2% and for screen-detected type 2 diabetes 1.7%, 3.4% and 3.6% (p<0.01). Men with high exposure to unemployment had a higher risk for pre-diabetes (OR 1.61, CI 95% 1.03-2.51) and screen-detected type 2 diabetes (OR 2.58 95% CI 1.23-5.44) than employed men, after adjustment for education, smoking, alcohol intake, physical activity and body mass index. Among women, associations were attenuated in the adjusted models. High exposure to unemployment may predispose to type 2 diabetes in middle-aged men. For clinicians, awareness of the patient's unemployment status may be helpful in recognizing undiagnosed cases.

Objective: Evidence from randomised controlled trials suggests that vitamin D may reduce multimorbidity, but very few studies have investigated specific determinants of vitamin D2 and D3 (two isoforms of 25-hydroxyvitamin D). The aim of the study was to investigate the determinants of vitamin D2 and D3 and to identify the risk factors associated with hypovitaminosis D. Design: Cross-sectional study. Setting: Northern Finland Birth Cohort 1966. Participants: 2374 male and 2384 female participants with data on serum 25(OH)D ₂ and 25(OH)D ₃ concentrations measured at 31 years of age (1997), together with comprehensive measures of daylight, anthropometric, social, lifestyle and contraceptive cofactors. Methods: We assessed a wide range of potential determinants prior to a nationwide fortification programme introduced in Finland. The determinants of 25(OH)D ₂ , 25(OH)D ₃ and 25(OH)D concentrations were analysed by linear regression and risk factors for being in lower tertile of 25(OH)D concentration by ordinal logistic regression. Results: At the time of sampling, 72% of the participants were vitamin D sufficient (≥50 nmol/L). Low sunlight exposure period (vs high) was associated positively with 25(OH)D ₂ and negatively with 25(OH)D ₃ concentrations. Use of oral contraceptives (vs non-users) was associated with an increase of 0.17 nmol/L (95% CI 0.08 to 0.27) and 0.48 nmol/L (95% CI 0.41 to 0.56) in 25(OH)D ₂ and 25(OH)D ₃ concentrations. Sex, season, latitude, alcohol consumption and physical activity were the factors most strongly associated with 25(OH)D concentration. Risk factors for low vitamin D status were low sunlight exposure defined by time of sampling, residing in northern latitudes, obesity, higher waist circumference, low physical activity and unhealthy diet. Conclusions: We demonstrate some differential associations of environmental and lifestyle factors with 25(OH)D ₂ and 25(OH)D ₃ raising important questions related to personalised healthcare. Future strategies could implement lifestyle modification and supplementation to improve vitamin D2 and D3 status, accounting for seasonal, lifestyle, metabolic and endocrine status.

Occupational exposure to pesticides has been reported among general population worldwide. However, little is known about the associations between non-occupational exposure to pesticides, and biological markers of health and their response by sex. We aimed to assess the associations between non-occupational overall pesticide exposure, length of exposure and specific pesticides reported with 35 biological markers of health representing cardiometabolic, haematological, lung function, sex hormones, liver and kidney function profiles, and vitamin D in Finnish cohort. 31-year cross-sectional examination of the Northern Finland Birth Cohort 1966 provided blood samples for biomarker measurements in 1997-1998. Number of subjects varied between 2361 and 5037 for given exposures and certain outcome associations. Multivariable regression analyses were performed to examine associations between overall pesticide exposure (OPE), length of pesticide exposure in months (PEM), in years (PEY), and specific pesticides use (PEU) or not with cardiometabolic [SBP, DBP, TC, LDL, HDL, triglycerides, fasting glucose, insulin, HOMA-IR, HOMA-B, HOMA-S, hs-CRP], hematological [WBC, RBC, Hb, HCT, MCV, MCH, MCHC, platelets], lung function (FVC, FEV1), sex hormones [luteinizing hormone (LH), testosterone (TT), sex-hormone binding globulin (SHBG)], liver and kidney function profiles [total protein, albumin, globulin, ALP, ALT, GGT, urea, creatinine], and vitamin D adjusting for sex, BMI, socioeconomic position (SEP) and season of pesticide use. This cohort study on up to 5037 adults with non-occupational OPE, PEM, PEY and PEU differed by sex and SEP. In regression analyses, all the exposures were positively associated with total cholesterol and low-density lipoprotein cholesterol, and PEU was negatively associated with high-density lipoprotein cholesterol in females. OPE and PEM were positively associated with haematocrit in females and PEU with platelets in males. PEU was negatively associated with mean corpuscular haemoglobin. OPE and PEM were positively associated with LH in males. OPE was negatively associated with total protein and albumin in males. In Finnish young adults, non-occupational overall pesticide exposure, length of exposure and specific pesticides were associated with multiple biological markers of health. The biological markers seem to be indicative of adverse effects of pesticides and warrant for further studies to replicate the findings and determine the underlying mechanisms.

Arctic Monitoring and Assessment Programme (AMAP) monitors persistent organic pollutant (POP) levels in the Arctic populations and assesses health effects related to exposure to them. Many internationally regulated POPs persist in humans and biota, while new Emerging Contaminants of Arctic Concern (ECAC), many of which are unregulated, present additional challenges. Biomonitoring offers valuable insights into temporal trends within human matrices, revealing critical information not only about the efficacy of international regulations but also serving as an early warning system for exposure and risks for human health. Data analyzed in this study is aggregated data presented in the AMAP Human Health in the Arctic assessments, which provide data on contaminant concentrations measured in human matrices from adults, and children across various population studies conducted in the Arctic since the 1980 s. Linear regression analyses were used to assess trends of various POPs including organochlorine (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and per- and polyfluoroalkyl substances (PFAS), measured over time from the Arctic populations in Finland, Norway, Sweden, Denmark, Iceland, Canada and Alaska (USA). Overall, decreasing trends were observed for PCBs and OCPs. Regulated PFAS showed decreasing trends, but increasing trends were observed for unregulated PFAS in certain populations. PBDEs showed decreasing or inconsistent trends in certain Arctic populations. Decreasing trends are observed for legacy POPs, but the trends for new emerging contaminants are inconsistent. More focus is needed on biomonitoring the new emerging contaminants of concern in the Arctic and their implications on human health.