Table 1 Studies assessing the effect of environmental exposures on epigenetics in human PD cases.
From: Linking environmental risk factors with epigenetic mechanisms in Parkinson’s disease
Study | Sample size | Epigenetic measure | Tissue | Exposure | Main results |
|---|---|---|---|---|---|
Chuang et al.35 | Blood: Controls = 215 (PEG1 cohort); 2100 (WHI cohort), Saliva: Cases = 127 (PEG2 cohort), Controls = 129 (PEG2 cohort) | DNA methylation | Blood, saliva | Coffee consumption | • Hypomethylation of cg21566642 near ALPPL2 in blood linked to coffee consumption in controls at genome-wide significance • Five CpGs significant at P < 5.0 × 10−6 (annotated to BSCL2, PODXL, CNTN4, GPR132 and ROBO3) • No significant associations in saliva of PD cases or controls |
Coupland et al.111 | Leucocyte: Cases = 358, Controls = 1084; Brain cohort 1 (cerebellum): Controls = 69; Brain cohort 2 (cerebellum, anterior cingulate cortex, putamen): Cases = 28, Controls = 12 | DNA methylation | Leucocytes, post-mortem brain | Vitamin E, PD drugs | • MAPT hypermethylation associated with vitamin E levels in leucocyte controls • Reduced MAPT methylation with levodopa use in leucocyte PD cases |
Paul et al.115 | SGPD: Cases = 959, Controls = 930; PEG: Cases = 569, Controls = 238 | DNA methylation | Whole blood | Lead | • PD status strongly associated with DNA hypermethylation-derived predicted lead levels in the tibial bone, but not the patella bone |
Go et al.113 | Cases = 20 (blood, brain) | DNA methylation | Blood, post-mortem brain | Organochlorine pesticide | • Seven DMPs in PD post-mortem brain with 10+ years plantation work (top two hypermethylated and annotated to PTGDS and PEX19) • 123 DMPs in blood (top two hypermethylated and annotated to WNT16 and ENTPD8) |
Oliveira et al.112 | Cases = 10, Controls = 9 | Global H4 acetylation | Blood | Grape juice and exercise | • Global increase in H4 acetylation in blood of PD patients in response to exercise and grape juice treatment • No differences between exercise alone and exercise plus grape juice |
Henderson-Smith et al.45 | Cases = 189, Controls = 191 | DNA methylation | Blood | PD drugs | • 237 DMPs PD patients taking dopamine replacement therapies (between 0.63% reduction and 0.86% increase in DNA methylation per year). |
Paul et al.117 | Blood: Cases = 342, Controls = 238 (PEG1 cohort); Saliva: Cases = 128, Controls = 131 (PEG2 cohort) | DNA methylation | Blood, saliva | Organophosphate (OP) pesticides | • Seven DMPs associated with OP exposure in PD (annotated to ALOX12, HLA, HLA-L, HLA-DPA1, POLR1B and HDAC4). |
Castillo et al.114 | Cases = 97 (high-mining area = 45, low-mining area = 52), Controls = 111 (high-mining area = 52, low-mining area = 59) | DNA methylation | Whole blood | Heavy metal mining | • Lower DNAm levels in controls low mining towns • No difference seen in PD cases |
Searles Nielsen et al.116 | Cases = 49, Controls = 103, Intermediate Controls (UPDRS3 ≥ 6 to <15) = 49 | DNA methylation | Whole blood | Manganese | • Inverse association between NOS2 methylation and welding • CpG site 8329 decreased in methylation with each year of welding exposure |
Searles Nielsen et al.120 | Cases = 292, Controls = 401 | DNA methylation | PBMC | Smoking | • No association between LINE-1 methylation and PD in PBMCs • Suggestive association between ever-smoking and PD; strongest in participants with low LINE-1 methylation |
