Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n=1522, age 32–72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation. DNA methylation was measured using the same instrument in a study of patients with anxiety disorders recruited at the Max Planck Institute of Psychiatry (MPIP, 131 non-medicated cases and 169 controls). To expand our mechanistic understanding, these findings were reverse translated in a mouse model of acute social defeat stress. In the KORA study, participants were classified according to mild, moderate, or severe levels of anxiety (29.4%/6.0%/1.5%, respectively). Severe anxiety was associated with 48.5% increased methylation at a single CpG site (cg12701571) located in the promoter of the gene encoding Asb1 (β-coefficient=0.56 standard error (SE)=0.10, p (Bonferroni)=0.005), a protein hypothetically involved in regulation of cytokine signaling. An interaction between IL-18 and severe anxiety with methylation of this CpG cite showed a tendency towards significance in the total population (p=0.083) and a significant interaction among women (p=0.014). Methylation of the same CpG was positively associated with Panic and Agoraphobia scale (PAS) scores (β=0.005, SE=0.002, p=0.021, n=131) among cases in the MPIP study. In a murine model of acute social defeat stress, Asb1 gene expression was significantly upregulated in a tissue-specific manner (p=0.006), which correlated with upregulation of the neuroimmunomodulating cytokine interleukin 1 beta. Our findings suggest epigenetic regulation of the stress-responsive Asb1 gene in anxiety-related phenotypes. Further studies are necessary to elucidate the causal direction of this association and the potential role of Asb1-mediated immune dysregulation in anxiety disorders.

At least 21 prescription drug groups have been associated with increased fracture risk.^1-12 The list includes some of the most commonly used products in the United States, such as opioids, proton pump inhibitors (PPIs), serotonin reuptake inhibitors (SSRIs), and sedatives.¹³ The wide use of many fracture-associated drugs (FADs) suggests that concurrent receipt of 2 or more may be prevalent. This in turn raises concern for fracture risk associated with such exposure. Logic suggests that risk will increase with the addition of each additional FAD. However, the fracture risk of such combined drug use has not been quantified. Understanding the prevalence of concurrent FAD exposure and its risk is especially important to older people, who have the highest baseline rate of fragility fracture and who are most likely to receive multiple FADs as diagnoses and treatments accumulate with age.

Purpose: To review the childhood risk factors for pediatric cancer (diagnosis before age 20). Methods: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 3 March 2021. Results: Strong evidence indicates that an array of genetic and epigenetic phenomena, structural birth defects, and chromosomal anomalies are associated with an increased risk of various childhood cancers. Increased risk is also associated with prior cancer, likely due to previous treatment agents and therapeutic ionizing radiation. Convincing evidence supports associations between several pediatric cancers and ionizing radiation, immunosuppression, and carcinogenic virus infection both in healthy children and in association with immune suppression following organ transplantation. Breastfeeding and a childhood diet rich in fruits and vegetables appears to reduce the risk of pediatric leukemia but the evidence is less strong. Childhood vaccination against carcinogenic viruses is associated with a lower risk of several cancers; there is less strong evidence that other childhood vaccinations more broadly may also lower risk. Ultraviolet (UV) radiation is associated with increased melanoma risk, although most melanomas following childhood UV exposure occur later, in adulthood. Evidence is weak or conflicting for the role of body mass index, other childhood infections, allergies, and certain treatments, including immunomodulator medications and human growth therapy.

This study aimed to examine prospectively the influence of exposure to job insecurity during working life on subjective well-being (SWB) after retirement, an association which has not been studied to date.Data were derived from the prospective population-based MONICA/KORA study conducted in southern Germany. Participants were recruited and data were collected during three independent surveys between 1984-1995 (T1) and followed up in 2009 (T2). The study sample consisted of 1801 employed participants (1146 male/ 655 female) aged 41-72 years at T1 and ≥65 years at T2, without missing data. Self-administered questionnaires and clinical examinations were used to assess job insecurity and risk factors at T1 and SWB at T2. Mean follow-up was 19.6 years. Logistic regression analyses were performed to determine the association of job insecurity with SWB after retirement. We accounted for an extensive set of sociodemographic, lifestyle-, health- and work-related risk factors.At T1, 39.5% of the participants reported job insecurity, which was associated with a 1.40-fold [95% confidence interval (95% CI) 1.08-1.82] risk of low SWB at T2 in models adjusted for sociodemographic and lifestyle- and health-related conditions at T1. Additional adjustment for a set of work-related risk factors at T1 had little effect on this association.Exposure to job insecurity at midlife was associated with low SWB in retirement, even after controlling for an extensive set of risk factors. This shows that the negative effects of unstable working conditions might persist well into retirement, long after cessation of employment.