Table 2:
Putative functions of genes in which the top exposure-associated DNAm sites sit; with details of how many sites within that gene were identified, and in which main analysis EWAS they were identified.
| Gene | Chr | Functional relevance | MBMS | MESA | |||
|---|---|---|---|---|---|---|---|
| Black NH | White NH | Black NH | White NH | Hispanic | |||
| ZNF286B | 17 | A pseudogene, which is predicted to be involved in regulation of RNA polymerase 2 (Pol II)-mediated transcription (Pol II transcribes protein-coding genes into mRNA41). | Born in a Jim Crow state: 1 | ||||
| PLXND1 | 3 | Encodes a cell receptor involved in axonal guidance, migration of endothelial cells, and regulates atherosclerotic plaque deposition42. | <HS education: 1 | ||||
| FUT6 | 19 | A Golgi stack membrane protein that is involved in basophil-mediated allergic inflammation43. | residential racialized economic segregation: 1 | ||||
| KLF6 | 10 | A transcriptional activator and tumour suppressor, which regulates macrophage inflammatory responses44. | LAC: 2 NOx: 3 | LAC: 1 NOx: 1 | |||
| FOS | 14 | FOS is an early-response gene, and is a subunit of the AP-1 transcription factor complex, which regulates gene expression involved in lung injury, repair and transformation45, as well as regulating many cytokine genes and T-cell differentiation46,47. | LAC: 1 NOx: 7 | ||||
| FOSB | 19 | FOSB is another subunit of AP-1. | LAC: 1 NOx: 1 | ||||
| ZFP36 | 19 | ZFP36 encodes a protein (TTP) that is a key regulator of post-transcriptional regulation, which has roles in immune and inflammatory responses48. | NOx: 2 | ||||
| DUSP1 | 5 | DUSP1 is a gene that regulates airway inflammation; DUSPl’s key mechanism of inflammation modulation may be via modulating the actions of the protein TTP encoded by the ZFP36 gene49. | LAC: 1 NOx: 1 | ||||
| VIM | 10 | Encodes a filament protein responsible for integrity of cell shape and cytoplasm. Pathogens can attach to this protein on the cell surface. Putative involvement regulating innate immune response to lung injury and irritation50 | NOx: 1 | ||||
| PDE4D | 5 | PDE4s, including PDE4D, have roles in cell signalling, as well as regulating inflammatory responses51. | MDS: 1 | ||||
| MALAT1 | 11 | Metastasis associated lung adenocarcinoma transcript 1, IncRNA that acts as transcriptional regulator; upregulation linked to cancerous tissues and proliferation and metastasis of tumour cells | LAC: 1 | ||||
| CYTIP | 2 | Modulates activation of ARF (ADP-ribosylation factor) genes, which regulate vesicle budding, tethering and cytoskeleton organization. Dysregulation of ARFs may be involved in cancer cell migration and invasion. | LAC: 1 NOx: 1 | ||||
| ZEB2 | 2 | DNA-binding transcriptional repressor involved in the transforming growth factor-P (TGF-P) signalling pathway that interacts with activated SMADs. May be related to small cell lung cancer52. | LAC: 1 NOx: 1 | ||||
| PTPRC | 1 | A receptor-type PTP that is an essential regulator of T- and B-cell antigen receptor signalling. | LAC: 1 NOx: 1 | ||||
| NPNT | 4 | An extracellular matrix protein that has roles in kidney development and carcinogenesis53. | LAC: 1 | ||||
| ADPRHL1 | 13 | a protein encoding a pseudoenzyme involved in cardiogenesis54. | NOx: 1 | ||||