Low antibody levels associated with significantly increased rate of SARS-CoV-2 infection in a highly vaccinated population from the US National Basketball Association.

SARS-CoV-2 antibody levels may serve as a correlate for immunity and could inform optimal booster timing. The relationship between antibody levels and protection from infection was evaluated in vaccinated individuals from the US National Basketball Association who had antibody levels measured at a single time point from September 12, 2021, to December 31, 2021. Cox proportional hazards models were used to estimate the risk of infection within 90 days of serologic testing by antibody level (<250, 250-800, and >800 AU/mL1 ), adjusting for age, time since last vaccine dose, and history of SARS-CoV-2 infection. Individuals were censored on date of booster receipt. The analytic cohort comprised 2323 individuals and was 78.2% male, 68.1% aged ≤40 years, and 56.4% vaccinated (primary series) with the Pfizer-BioNTech mRNA vaccine. Among the 2248 (96.8%) individuals not yet boosted at antibody testing, 77% completed their primary vaccine series 4-6 months before testing and the median (interquartile range) antibody level was 293.5 (interquartile range: 121.0-740.5) AU/mL. Those with levels <250 AU/mL (adj hazard ratio [HR]: 2.4; 95% confidence interval [CI]: 1.5-3.7) and 250-800 AU/mL (adj HR: 1.5; 95% CI: 0.98-2.4) had greater infection risk compared to those with levels >800 AU/mL. Antibody levels could inform individual COVID-19 risk and booster scheduling.

Urinary glyphosate and AMPA levels in a cross-sectional study of postmenopausal women: Associations with organic eating behavior and dietary intake.

Animal and epidemiologic studies suggest that there may be adverse health effects from exposure to glyphosate, the most highly used pesticide in the world, and its metabolite aminomethylphosphonic acid (AMPA). Meanwhile, consumption of organic foods (presumably grown free of chemical pesticides) has increased in recent years. However, there have been limited biomonitoring studies assessing the levels of human glyphosate and AMPA exposure in the United States. We examined urinary levels of glyphosate and AMPA in the context of organic eating behavior in a cohort of healthy postmenopausal women residing in Southern California and evaluated associations with demographics, dietary intake, and other lifestyle factors. 338 women provided two first-morning urine samples and at least one paired 24-h dietary recall reporting the previous day's dietary intake. Urinary glyphosate and AMPA were measured using LC-MS/MS. Participants reported on demographic and lifestyle factors via questionnaires. Potential associations were examined between these factors and urinary glyphosate and AMPA concentrations. Glyphosate was detected in 89.9% of urine samples and AMPA in 67.2%. 37.9% of study participants reported often or always eating organic food, 30.2% sometimes, and 32.0% seldom or never. Frequency of organic food consumption was associated with several demographic and lifestyle factors. Frequent organic eaters had significantly lower urinary glyphosate and AMPA levels, but not after adjustment for covariates. Grain consumption was significantly associated with higher urinary glyphosate levels, even among women who reported often or always eating organic grains. Soy protein and alcohol consumption as well as high frequency of eating fast food were associated with higher urinary AMPA levels. In conclusion, in the largest study to date examining paired dietary recall data and measurements of first-void urinary glyphosate and AMPA, the vast majority of subjects sampled had detectable levels, and significant dietary sources in the American diet were identified.

Association of Glyphosate Exposure with Blood DNA Methylation in a Cross-Sectional Study of Postmenopausal Women.

BACKGROUND: Glyphosate is the most commonly used herbicide in the world and is purported to have a variety of health effects, including endocrine disruption and an elevated risk of several types of cancer. Blood DNA methylation has been shown to be associated with many other environmental exposures, but to our knowledge, no studies to date have examined the association between blood DNA methylation and glyphosate exposure. OBJECTIVE: We conducted an epigenome-wide association study to identify DNA methylation loci associated with urinary glyphosate and its metabolite aminomethylphosphonic acid (AMPA) levels. Secondary goals were to determine the association of epigenetic age acceleration with glyphosate and AMPA and develop blood DNA methylation indices to predict urinary glyphosate and AMPA levels. METHODS: For 392 postmenopausal women, white blood cell DNA methylation was measured using the Illumina Infinium MethylationEPIC BeadChip array. Glyphosate and AMPA were measured in two urine samples per participant using liquid chromatography-tandem mass spectrometry. Methylation differences at the probe and regional level associated with glyphosate and AMPA levels were assessed using a resampling-based approach. Probes and regions that had an false discovery rate q<0.1 in ≥90% of 1,000 subsamples of the study population were considered differentially methylated. Differentially methylated sites from the probe-specific analysis were combined into a methylation index. Epigenetic age acceleration from three epigenetic clocks and an epigenetic measure of pace of aging were examined for associations with glyphosate and AMPA. RESULTS: We identified 24 CpG sites whose methylation level was associated with urinary glyphosate concentration and two associated with AMPA. Four regions, within the promoters of the MSH4, KCNA6, ABAT, and NDUFAF2/ERCC8 genes, were associated with glyphosate levels, along with an association between ESR1 promoter hypomethylation and AMPA. The methylation index accurately predicted glyphosate levels in an internal validation cohort. AMPA, but not glyphosate, was associated with greater epigenetic age acceleration. DISCUSSION: Glyphosate and AMPA exposure were associated with DNA methylation differences that could promote the development of cancer and other diseases. Further studies are warranted to replicate our results, determine the functional impact of glyphosate- and AMPA-associated differential DNA methylation, and further explore whether DNA methylation could serve as a biomarker of glyphosate exposure. https://doi.org/10.1289/EHP10174.

Association of mammographic density with blood DNA methylation.

BACKGROUND: Altered DNA methylation may be an intermediate phenotype between breast cancer risk factors and disease. Mammographic density is a strong risk factor for breast cancer. However, no studies to date have identified an epigenetic signature of mammographic density. We performed an epigenome-wide association study of mammographic density. METHODS: White blood cell DNA methylation was measured for 385 postmenopausal women using the Illumina Infinium MethylationEPIC BeadChip array. Differential methylation was assessed using genome-wide, probe-level, and regional analyses. We implemented a resampling-based approach to improve the stability of our findings. RESULTS: On average, women with elevated mammographic density exhibited DNA hypermethylation within CpG islands and gene promoters compared to women with lower mammographic density. We identified 250 CpG sites for which DNA methylation was significantly associated with mammographic density. The top sites were located within genes associated with cancer, including HDLBP, TGFB2, CCT4, and PAX8, and were more likely to be located in regulatory regions of the genome. We also identified differential DNA methylation in 37 regions, including within the promoters of PAX8 and PF4, a gene involved in the regulation of angiogenesis. Overall, our results paint a picture of epigenetic dysregulation associated with mammographic density. CONCLUSION: Mammographic density is associated with differential DNA methylation throughout the genome, including within genes associated with cancer. Our results suggest the potential involvement of several genes in the biological mechanisms behind differences in breast density between women. Further studies are warranted to explore these potential mechanisms and potential links to breast cancer risk.