DNA methylation biomarker for cumulative lead exposure is associated with Parkinson’s disease

Paul, Kimberly C.; Horvath, Steve; Rosario, Irish Del; Bronstein, Jeff M.; Ritz, Beate

doi:10.1186/s13148-021-01051-3

Cited by 20 publications

(14 citation statements)

References 17 publications

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“…This finding remained significant after adjustment for other risk factors, including acid rain (p = 0.0119). These findings are consistent with several epidemiologic studies in PD, including case-control studies of lead in bone and biomarkers of blood methylation [2] , [3] .…”

Section: Discussionsupporting

confidence: 91%

“…With the exception of the synthetic chemical MPTP, few environmental risk factors have been consistently identified [1] . However, considerable evidence implicates exposure to some pesticides and metals, particularly lead [2] , [3] . We recently reported that state-wide prevalence rates for PD in the U.S. are highly correlated with the quantity of acid rain received per state.…”

Section: Introductionmentioning

confidence: 99%

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Lead service lines and Parkinson’s disease prevalence in U.S. States

Schwartz

Williamson

2021

Clinical Parkinsonism & Related Disorders

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Introduction We recently showed that the prevalence of Parkinson’s Disease (PD) in U.S. states is positively associated with the quantity of acid rain. Acid rain could play an etiologic role in PD by mobilizing metals, e.g., lead, from watersheds and pipes into drinking water. We assessed the correlation of PD with lead service lines, the underground pipes that connect homes to municipal water sources, which are a major aqueous source of lead. Methods We used multiple regression techniques to examine PD prevalence rates by state relative to the number of lead service lines. We included known or suspected aqueous risk factors, e.g., the Acid Precipitation Index (a measure of acid rain) and well water use. Results Age-, race-, and sex-adjusted prevalence rates for PD were significantly and positively correlated with the log number of lead service lines (p = 0.0004). The effect of lead service lines remained significant after adjusting for the effects of acid rain and well water use (p = 0.0019). Conclusion These findings are consistent with a role for lead in the etiology of PD. Studies of lead service line exposure in relation to PD at the individual level are warranted.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Lead service lines and Parkinson’s disease prevalence in U.S. States

Schwartz

Williamson

2021

Clinical Parkinsonism & Related Disorders

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“…A recent meta-analysis demonstrated that changes in infant cord blood DNA methylation at thousands of CpG sites were linked to maternal smoking . Many smoking-related DNA methylation changes persist into later life, are sensitive to the level of maternal or adult smoking, and are reflective of the time since quitting. − DNA methylation biomarkers have also been identified for other exposures, such as alcohol and the metal lead, − although few are as robust and extensively studied as smoking. Such comprehensive exposure and methylation data in the same human samples are lacking for many toxicants, necessitating further research.…”

Section: Challenges and Opportunities In Toxicoepigeneticsmentioning

confidence: 99%

Toxicoepigenetics and Environmental Health: Challenges and Opportunities

Svoboda

Perera

Morgan

et al. 2022

Chem. Res. Toxicol.

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The rapidly growing field of toxicoepigenetics seeks to understand how toxicant exposures interact with the epigenome to influence disease risk. Toxicoepigenetics is a promising field of environmental health research, as integrating epigenetics into the field of toxicology will enable a more thorough evaluation of toxicant-induced disease mechanisms as well as the elucidation of the role of the epigenome as a biomarker of exposure and disease and possible mediator of exposure effects. Likewise, toxicoepigenetics will enhance our knowledge of how environmental exposures, lifestyle factors, and diet interact to influence health. Ultimately, an understanding of how the environment impacts the epigenome to cause disease may inform risk assessment, permit noninvasive biomonitoring, and provide potential opportunities for therapeutic intervention. However, the translation of research from this exciting field into benefits for human and animal health presents several challenges and opportunities. Here, we describe four significant areas in which we see opportunity to transform the field and improve human health by reducing the disease burden caused by environmental exposures. These include (1) research into the mechanistic role for epigenetic change in environment-induced disease, (2) understanding key factors influencing vulnerability to the adverse effects of environmental exposures, (3) identifying appropriate biomarkers of environmental exposures and their associated diseases, and (4) determining whether the adverse effects of environment on the epigenome and human health are reversible through pharmacologic, dietary, or behavioral interventions. We then highlight several initiatives currently underway to address these challenges.

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“…Recently, Paul and coworkers showed that Parkinson’s disease can also be associated with exposure to Pb through epigenetic mechanisms [ 128 ].…”

Section: Link Between Toxicants Exposure Dna Methylation and Brain Ev...mentioning

confidence: 99%

Evolutionary Implications of Environmental Toxicant Exposure

et al. 2022

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Homo sapiens have been exposed to various toxins and harmful compounds that change according to various phases of human evolution. Population genetics studies showed that such exposures lead to adaptive genetic changes; while observing present exposures to different toxicants, the first molecular mechanism that confers plasticity is epigenetic remodeling and, in particular, DNA methylation variation, a molecular mechanism proposed for medium-term adaptation. A large amount of scientific literature from clinical and medical studies revealed the high impact of such exposure on human biology; thus, in this review, we examine and infer the impact that different environmental toxicants may have in shaping human evolution. We first describe how environmental toxicants shape natural human variation in terms of genetic and epigenetic diversity, and then we describe how DNA methylation may influence mutation rate and, thus, genetic variability. We describe the impact of these substances on biological fitness in terms of reproduction and survival, and in conclusion, we focus on their effect on brain evolution and physiology.

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DNA methylation biomarker for cumulative lead exposure is associated with Parkinson’s disease

Cited by 20 publications

References 17 publications

Lead service lines and Parkinson’s disease prevalence in U.S. States

Lead service lines and Parkinson’s disease prevalence in U.S. States

Toxicoepigenetics and Environmental Health: Challenges and Opportunities

Evolutionary Implications of Environmental Toxicant Exposure

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