Genetic evidence for the association between per- and polyfluoroalkyl substances exposure and rheumatoid arthritis risk

Association between plasma levels of per- and polyfluoroalkyl substances and schizophrenia: A case-control study.

Per- and polyfluoroalkyl substances (PFAS) are a class of neurotoxic persistent organic pollutants that may increase the risk of cognitive impairment and dementia, yet their association with schizophrenia (SCZ) remains unclear. This study aimed to investigate the relationship between plasma PFAS levels and the risk of schizophrenia. The concentrations of PFAS in plasma were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). To evaluate the single and combined effects of PFAS exposure on the risk of schizophrenia, we employed multivariable logistic regression, restricted cubic splines (RCS), Bayesian kernel machine regression (BKMR), and generalized weighted quantile sum (gWQS) models. Logistic regression analysis revealed that, compared with the lowest quartile (Q1), the odds ratios (ORs) for PFOS and PFHxS in the highest quartile (Q4) were 0.17 (95% CI:0.09∼0.36) and 0.39 (95% CI:0.21∼0.71), respectively. RCS analysis suggested nonlinear relationships between PFUnDA, PFOS, PFOA, and PFHxS and schizophrenia. In the assessment of mixture exposure effects, the BKMR model indicated an overall negative association between PFAS mixtures and schizophrenia risk, and gWQS analysis further identified PFHxS as the component with the highest weight contribution. Additionally, correlations were observed between the levels of PFUnDA, PFOS, and PFHxS and inflammatory indices in patients with schizophrenia. Future large-scale prospective studies combined with toxicological mechanism research are needed to further validate these findings.

Correlation between perfluoroalkyl and polyfluoroalkyl substances and adult asthma in the NHANES

The inverse link between PFAS co-exposure and asthma incidence persisted across multi-pollutant models, weighted quantile sum regression, and Bayesian kernel machine regression models, with PFOS emerging as the primary negative influencer.

Associations between per- and polyfluoroalkyl substances and semen parameters: An updated systematic review and meta-analysis.

Environmental exposure to per- and polyfluoroalkyl substances (PFAS) rises concerns about male reproductive health. Despite a wide body of experimental evidence supporting the biological role of PFAS exposure in male reproductive effects, available epidemiological studies are variably consistent about this association. Four databases were searched up to July 13, 2025 (PROSPERO: CRD420251267798). The systematic review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included that assessed the association of PFAS on sperm outcomes. The primary effect measure was the Pearson correlation coefficient (r). Outcomes included sperm concentration, semen volume, total sperm count, motility, morphology, pH, and sperm DNA fragmentation, Fourteen studies including 7465 participants were included in this review. The results of meta-analyses indicate heterogeneous patterns of association, with PFAS mixtures showing limited associations with conventional semen parameters but demonstrating consistent inverse relationships with progressive motility (correlation scale [r] = -0.058, 95% confidence interval [CI]: -0.100 to -0.015) and sperm deoxyribonucleic acid (DNA) integrity (r = 0.141, 95% CI: 0.087-0.195). Individual congeners exhibited distinct association profiles, suggesting potential congener-specific effects on male reproductive function. The consistent association between increased DNA fragmentation across PFAS metrics suggest a possible role in unexplained male infertility and prompts further investigation.

Per- and polyfluoroalkyl substances mixture exposure is associated with colorectal cancer TNM stage

It is suggested that higher plasma PFAS concentrations, particularly HFPO-DA, may be associated with more advanced TNM stage in colorectal cancer and warrant confirmation in larger prospective studies.

Revealing the Link Between Exposure to Per- and Polyfluoroalkyl Substances (PFAS) and Stroke: A Comprehensive Epidemiological and Network Toxicology Perspective

Association of perfluoroalkyl and polyfluoroalkyl substances with polyendocrine metabolic ovarian syndrome and endocrine abnormalities: A case-control study.

BACKGROUND Polyendocrine metabolic ovarian syndrome (PMOS) is a systemic endocrine and metabolic disorder that has been increasingly linked to exposure to environmental endocrine-disrupting chemicals. Although perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been implicated as potential contributors, the combined health effects of PFASs mixtures and the potential pathways linking PFAS exposure to endocrine abnormalities remain incompletely understood. METHODS In this hospital-based case-control study, 109 women with PMOS and 96 healthy controls were recruited. Serum concentrations of 19 PFASs were measured using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS), and 11 PFASs congeners with detection frequencies exceeding 80% were included in subsequent analyses. Bayesian logistic regression and dose response analyses were used to evaluate the associations of individual PFASs with PMOS risk and endocrine biomarkers, while generalized additive models were used to characterize potential nonlinear exposure response relationships. The combined effects of PFASs mixtures were evaluated using quantile g-computation (Qgcomp) and weighted quantile sum (WQS) regression. Propensity score overlap weighting was used in sensitivity analyses to assess the robustness of the findings with respect to baseline differences in age and BMI. Exploratory mediation analyses were conducted using circulating hormone ratios related to steroidogenesis as surrogate markers to evaluate potential statistical indirect effect signals. RESULTS Eleven PFASs were included in the statistical analyses: PFBA, PFOA, PFBS, PFPeS, PFTrDA, PFHpS, PFOS, PFDS, PFHxS, PFNA, and 6:2 Cl-PFESA. PFDS, PFBA, PFHxS, and 6:2 Cl-PFESA were associated with higher PMOS risk and elevated total testosterone (TT) levels, whereas PFPeS, PFTrDA, and PFDS were associated with a lower FSH/LH ratio. Mixture analyses consistently showed that combined PFASs exposure was associated with higher PMOS risk, elevated TT levels, and a lower FSH/LH ratio. PFDS showed the largest relative contribution to the mixture associations with PMOS risk and TT levels, whereas PFTrDA showed the largest relative contribution to the association with a lower FSH/LH ratio. Sensitivity analyses using overlap weighting were broadly concordant with the primary analyses. The overall association between PFASs mixtures and PMOS remained statistically significant after overlap weighting (β = 0.57, 95% CI: 0.44-0.69). In addition, the inverse associations of PFTrDA, PFPeS, and PFDS with the FSH/LH ratio and the positive associations of PFDS and 6:2 Cl-PFESA with TT remained statistically significant. Exploratory mediation analysis identified a statistically significant indirect effect involving the circulating DHT/TT ratio, which was used as an exploratory surrogate marker of androgen conversion related to SRD5A. This indirect effect accounted for 25.9% of the association between PFDS and PMOS. CONCLUSIONS PFASs mixture exposure was associated with higher PMOS risk, elevated TT levels, and a lower FSH/LH ratio. PFDS and PFTrDA showed relatively large contributions to the observed mixture associations. Exploratory mediation analysis further identified an indirect effect involving the circulating DHT/TT ratio in the association between PFDS and PMOS; however, the biological relevance of this finding requires further mechanistic validation.