Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Singh, Anmol, Zhong, Yizhen, Nahlawi, Layan, Park, C. Sehwan, De, Tanima, Alarcon, Cristina, Perera, Minoli A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958994/
https://www.ncbi.nlm.nih.gov/pubmed/33691021
_version_ 1783664897520828416
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
work_keys_str_mv AT singhanmol incorporationofdnamethylationintoeqtlmappinginafricanamericans
AT zhongyizhen incorporationofdnamethylationintoeqtlmappinginafricanamericans
AT nahlawilayan incorporationofdnamethylationintoeqtlmappinginafricanamericans
AT parkcsehwan incorporationofdnamethylationintoeqtlmappinginafricanamericans
AT detanima incorporationofdnamethylationintoeqtlmappinginafricanamericans
AT alarconcristina incorporationofdnamethylationintoeqtlmappinginafricanamericans
AT pereraminolia incorporationofdnamethylationintoeqtlmappinginafricanamericans