Table 3.
Differentially methylated probes (DMPs) associated with urinary glyphosate and AMPA concentration in 332 postmenopausal California women.
Probe | Freq. | Median -value | Median FDR -value | Methylation () difference per unit glyphosate/AMPA | Chr. | Position (hg19) | Gene(s) | Gene summary | Location within gene(s) | CpG Island | Predicted chromatin state |
---|---|---|---|---|---|---|---|---|---|---|---|
Glyphosate | |||||||||||
cg13499896 | 1,000 | 0.006 | 22 | 18,571,657 | PEX26 | Probably required for protein import into peroxisomes. | 3’UTR | Open Sea | Strong enhancer | ||
cg24576174 | 1,000 | 0.010 | 11 | 65,828,083 | SF3B2 | Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex. | Body | Open Sea | Transcription elongation | ||
cg00355690 | 996 | 0.011 | 16 | 89,722,417 | CHMP1A | Involved in multivesicular body sorting of proteins to the interiors of lysosome. Involved in cytokinesis. May also be involved in chromosome condensation. May play a role in stable cell cycle progression and in PcG gene silencing. | Body | N. Shore | Weak enhancer | ||
cg26833395 | 1,000 | 0.012 | 20 | 30,102,102 | HM13 | Plays a key role in generating signal sequence-derived human lymphocyte antigen-E epitopes that are recognized by the immune system. | Promoter | Island | Weak promoter | ||
cg06993862 | 987 | 0.023 | 3 | 49,141,001 | QARS1 | Plays a critical role in brain development. | Body | N. Shore | Strong enhancer | ||
cg13310154 | 978 | 0.029 | 17 | 55,910,843 | — | — | Intergenic | Open Sea | Insulator | ||
cg16601151 | 959 | 0.031 | 16 | 19,079,341 | COQ7 | Involved in ubiquinone biosynthesis. Involved in lifespan determination in a ubiquinone-independent manner. | Body | Island | Active promoter | ||
cg26787244 | 965 | 0.034 | 11 | 644,011 | — | — | Intergenic | Island | Weak transcribed | ||
cg07261978 | 950 | 0.038 | 8 | 82,043,566 | — | — | Intergenic | Open Sea | Weak enhancer | ||
cg19029576 | 954 | 0.040 | 9 | 140,330,686 | ENTPD8 | Plays a central role in concentration of extracellular nucleotides. | Body | Island | Weak transcribed | ||
cg25629796 | 971 | 0.041 | 0.35 | 17 | 11,940,467 | MAP2K4 | Member of the mitogen-activated protein kinase (MAPK) family, which is involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. | Body | Open Sea | Weak transcribed | |
cg01430385 | 954 | 0.042 | 10 | 1,033,349 | GTPBP4 | Involved in the biogenesis of the 60S ribosomal subunit. | Promoter | N. Shore | Active promoter | ||
cg02519806 | 948 | 0.045 | 4 | 119,810,036 | SYNPO2 | Has an actin-binding and actin-bundling activity. Involved in regulation of cell migration; may be a tumor suppressor. | Promoter | Open Sea | Poised promoter | ||
cg04915788 | 959 | 0.044 | 12 | 25,156,888 | — | — | Intergenic | Open Sea | Weak enhancer | ||
cg13170005 | 957 | 0.048 | 17 | 4,690,632 | VMO1 | Unknown function, homolog of a gene that encodes component of the outer membrane of the vitelline layer of the egg in chickens. | Promoter | N. Shore | Repressed | ||
cg26483235 | 938 | 0.050 | 8 | 62,870,065 | — | — | Intergenic | Open Sea | Heterochromatin | ||
cg07318309 | 913 | 0.051 | 0.19 | 5 | 156,537,633 | HAVCR2 | Cell surface receptor implicated in modulating innate and adaptive immune responses | Promoter | Open Sea | Weak enhancer | |
cg07509511 | 913 | 0.051 | 2 | 65,297,852 | CEP68 | Involved in maintenance of centrosome cohesion | Body | Open Sea | Transcription elongation | ||
cg11062848 | 913 | 0.052 | 2.08 | 6 | 13,616,537 | NOL7 | Maintains nucleolar structure and cell growth rates; also functions as a tumor suppressor and regulator of angiogenesis. Expression regulated by the RB tumor suppressor gene. | Body | S. Shore | Active promoter | |
cg18722557 | 917 | 0.054 | 0.23 | 10 | 123,734,694 | NSMCE4A | Component of a complex involved in DNA double-strand breaks by homologous recombination. Required for telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. | Promoter | Island | Active promoter | |
cg20531550 | 923 | 0.054 | 7 | 128,550,902 | KCP | Enhances bone morphogenetic protein (BMP) signaling in a paracrine manner. | Promoter | Island | Weak transcribed | ||
cg05730283 | 933 | 0.055 | 0.42 | 2 | 62,422,808 | B3GNT2 | Probably constitutes the main polylactosamine synthase | Promoter | Island | Active promoter | |
cg20540608 | 901 | 0.053 | 1.53 | 5 | 60,241,003 | NDUFAF2; ERCC8 | NDUFAF2: Acts as a molecular chaperone for mitochondrial complex I assembly. ERCC8: Plays a role in DNA single-strand and double-strand breaks (DSSBs) repair; involved in repair of DSSBs by nonhomologous end joining (NHEJ) | Promoter | Island | Active promoter | |
cg25597976 | 929 | 0.055 | 1.05 | 8 | 74,750,772 | UBE2W | Promotes the ubiquitination of Fanconi anemia complementation group proteins and may be important in the repair of DNA damage | Body | Open Sea | Weak enhancer | |
AMPA | |||||||||||
cg22171277 | 938 | 0.038 | 0.32 | 2 | 70,363,119 | — | — | Intergenic | Open Sea | Strong enhancer | |
cg23261070 | 946 | 0.041 | 0.13 | 17 | 6,918,037 | C17orf49 | Component of chromatin complexes such as the MLL1/MLL and NURF complexes | Promoter | Island | Active promoter |
Note: Linear models adjusted for urinary creatinine, age, race/ethnicity, BMI, smoking status, alcohol consumption, self-reported organic eating habits, diet quality (HEI), estimated WBC type proportions, batch, and position on chip, were fitted for all probes on the Illumina HumanMethylationEPIC array which remained after quality filtering. Results were pooled from 1,000 random subsamples of the training set (individuals per subsample). Probes that were statistically significant with FDR in 90% or more subsamples were considered differentially methylated. Missing data for covariates (from individuals in the training set) were substituted with the median (numeric variables) or mode (categorical variables). Chromatin state is predicted by ChromHMM from ENCODE data for the GM12878 cell line. Gene summaries are condensed from the RefSeq and UniProt gene summaries and provide a broad overview of the known function(s) of the gene product. —, no data; AMPA, aminomethylphosphonic acid; BMI, body mass index; Chr, Chromosome; FDR, false discovery rate; Freq., number of iterations in which DMP was identified as significant; HEI, Healthy Eating Index; WBC, white blood cell.