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Incorporation of DNA methylation into eQTL mapping in African Americans
Epigenetics is a reversible molecular mechanism that plays a critical role in many developmental, adaptive, and disease processes. DNA methylation has been shown to regulate gene expression and the advent of high throughput technologies has made genome-wide DNA methylation analysis possible. We inve...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958994/ https://www.ncbi.nlm.nih.gov/pubmed/33691021 |
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author | Singh, Anmol Zhong, Yizhen Nahlawi, Layan Park, C. Sehwan De, Tanima Alarcon, Cristina Perera, Minoli A. |
author_facet | Singh, Anmol Zhong, Yizhen Nahlawi, Layan Park, C. Sehwan De, Tanima Alarcon, Cristina Perera, Minoli A. |
author_sort | Singh, Anmol |
collection | PubMed |
description | Epigenetics is a reversible molecular mechanism that plays a critical role in many developmental, adaptive, and disease processes. DNA methylation has been shown to regulate gene expression and the advent of high throughput technologies has made genome-wide DNA methylation analysis possible. We investigated the effect of DNA methylation on eQTL mapping (methylation-adjusted eQTLs), by incorporating DNA methylation as a SNP-based covariate in eQTL mapping in African American derived hepatocytes. We found that the addition of DNA methylation uncovered new eQTLs and eGenes. Previously discovered eQTLs were significantly altered by the addition of DNA methylation data suggesting that methylation may modulate the association of SNPs to gene expression. We found that methylation-adjusted eQTLs that were less significant compared to PC-adjusted eQTLs were enriched in lipoprotein measurements (FDR=0.0040), immune system disorders (FDR = 0.0042), and liver enzyme measurements (FDR=0.047), suggesting that DNA methylation modulates the genetic regulation of these phenotypes. Our methylation-adjusted eQTL analysis also uncovered novel SNP-gene pairs. For example, we found that the SNP, rs1332018, was associated to GSTM3. GSTM3 expression has been linked to Hepatitis B which African Americans suffer from disproportionately. Our methylation-adjusted method adds new understanding to the genetic basis of complex diseases that disproportionally affect African Americans. |
format | Online Article Text |
id | pubmed-7958994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-79589942021-03-15 Incorporation of DNA methylation into eQTL mapping in African Americans Singh, Anmol Zhong, Yizhen Nahlawi, Layan Park, C. Sehwan De, Tanima Alarcon, Cristina Perera, Minoli A. Pac Symp Biocomput Article Epigenetics is a reversible molecular mechanism that plays a critical role in many developmental, adaptive, and disease processes. DNA methylation has been shown to regulate gene expression and the advent of high throughput technologies has made genome-wide DNA methylation analysis possible. We investigated the effect of DNA methylation on eQTL mapping (methylation-adjusted eQTLs), by incorporating DNA methylation as a SNP-based covariate in eQTL mapping in African American derived hepatocytes. We found that the addition of DNA methylation uncovered new eQTLs and eGenes. Previously discovered eQTLs were significantly altered by the addition of DNA methylation data suggesting that methylation may modulate the association of SNPs to gene expression. We found that methylation-adjusted eQTLs that were less significant compared to PC-adjusted eQTLs were enriched in lipoprotein measurements (FDR=0.0040), immune system disorders (FDR = 0.0042), and liver enzyme measurements (FDR=0.047), suggesting that DNA methylation modulates the genetic regulation of these phenotypes. Our methylation-adjusted eQTL analysis also uncovered novel SNP-gene pairs. For example, we found that the SNP, rs1332018, was associated to GSTM3. GSTM3 expression has been linked to Hepatitis B which African Americans suffer from disproportionately. Our methylation-adjusted method adds new understanding to the genetic basis of complex diseases that disproportionally affect African Americans. 2021 /pmc/articles/PMC7958994/ /pubmed/33691021 Text en http://creativecommons.org/licenses/by/4.0/ Open Access chapter published by World Scientific Publishing Company and distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC) 4.0 License. |
spellingShingle | Article Singh, Anmol Zhong, Yizhen Nahlawi, Layan Park, C. Sehwan De, Tanima Alarcon, Cristina Perera, Minoli A. Incorporation of DNA methylation into eQTL mapping in African Americans |
title | Incorporation of DNA methylation into eQTL mapping in African Americans |
title_full | Incorporation of DNA methylation into eQTL mapping in African Americans |
title_fullStr | Incorporation of DNA methylation into eQTL mapping in African Americans |
title_full_unstemmed | Incorporation of DNA methylation into eQTL mapping in African Americans |
title_short | Incorporation of DNA methylation into eQTL mapping in African Americans |
title_sort | incorporation of dna methylation into eqtl mapping in african americans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958994/ https://www.ncbi.nlm.nih.gov/pubmed/33691021 |
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