Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain
- PMID: 20485568
- PMCID: PMC2869317
- DOI: 10.1371/journal.pgen.1000952
Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain
Abstract
A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We present a set of integrated experiments that investigate the effects of common genetic variability on DNA methylation and mRNA expression in four human brain regions each from 150 individuals (600 samples total). We find an abundance of genetic cis regulation of mRNA expression and show for the first time abundant quantitative trait loci for DNA CpG methylation across the genome. We show peak enrichment for cis expression QTLs to be approximately 68,000 bp away from individual transcription start sites; however, the peak enrichment for cis CpG methylation QTLs is located much closer, only 45 bp from the CpG site in question. We observe that the largest magnitude quantitative trait loci occur across distinct brain tissues. Our analyses reveal that CpG methylation quantitative trait loci are more likely to occur for CpG sites outside of islands. Lastly, we show that while we can observe individual QTLs that appear to affect both the level of a transcript and a physically close CpG methylation site, these are quite rare. We believe these data, which we have made publicly available, will provide a critical step toward understanding the biological effects of genetic variation.
Conflict of interest statement
The authors have declared that no competing interests exist.
Figures
Similar articles
-
Genetic control of individual differences in gene-specific methylation in human brain.Am J Hum Genet. 2010 Mar 12;86(3):411-9. doi: 10.1016/j.ajhg.2010.02.005. Am J Hum Genet. 2010. PMID: 20215007 Free PMC article.
-
Mendelian randomization integrating GWAS and mQTL data identified novel pleiotropic DNA methylation loci for neuropathology of Alzheimer's disease.Neurobiol Aging. 2021 Jan;97:18-27. doi: 10.1016/j.neurobiolaging.2020.09.019. Epub 2020 Oct 1. Neurobiol Aging. 2021. PMID: 33120085 Free PMC article.
-
The presence of methylation quantitative trait loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue.PLoS One. 2013;8(2):e55923. doi: 10.1371/journal.pone.0055923. Epub 2013 Feb 19. PLoS One. 2013. PMID: 23431366 Free PMC article.
-
Genome-wide associations between genetic and epigenetic variation influence mRNA expression and insulin secretion in human pancreatic islets.PLoS Genet. 2014 Nov 6;10(11):e1004735. doi: 10.1371/journal.pgen.1004735. eCollection 2014 Nov. PLoS Genet. 2014. PMID: 25375650 Free PMC article.
-
Genetic-epigenetic interactions in cis: a major focus in the post-GWAS era.Genome Biol. 2017 Jun 19;18(1):120. doi: 10.1186/s13059-017-1250-y. Genome Biol. 2017. PMID: 28629478 Free PMC article. Review.
Cited by
-
Genetic effects on the skin methylome in healthy older twins.Am J Hum Genet. 2024 Sep 5;111(9):1932-1952. doi: 10.1016/j.ajhg.2024.07.010. Epub 2024 Aug 12. Am J Hum Genet. 2024. PMID: 39137780 Free PMC article.
-
Characterizing a complex CT-rich haplotype in intron 4 of SNCA using large-scale targeted amplicon long-read sequencing.NPJ Parkinsons Dis. 2024 Jul 26;10(1):136. doi: 10.1038/s41531-024-00749-4. NPJ Parkinsons Dis. 2024. PMID: 39060285 Free PMC article.
-
Genetic control of DNA methylation is largely shared across European and East Asian populations.Nat Commun. 2024 Mar 28;15(1):2713. doi: 10.1038/s41467-024-47005-0. Nat Commun. 2024. PMID: 38548728 Free PMC article.
-
Comparing feature selection and machine learning approaches for predicting CYP2D6 methylation from genetic variation.Front Neuroinform. 2024 Feb 21;17:1244336. doi: 10.3389/fninf.2023.1244336. eCollection 2023. Front Neuroinform. 2024. PMID: 38449836 Free PMC article.
-
BISCUIT: an efficient, standards-compliant tool suite for simultaneous genetic and epigenetic inference in bulk and single-cell studies.Nucleic Acids Res. 2024 Apr 12;52(6):e32. doi: 10.1093/nar/gkae097. Nucleic Acids Res. 2024. PMID: 38412294 Free PMC article.
References
-
- Melzer D, Perry JR, Hernandez D, Corsi AM, Stevens K, et al. A genome-wide association study identifies protein quantitative trait loci (pQTLs). PLoS Genet. 2008;4:e1000072. doi: 10.1371/journal.pgen.1000072. - DOI - PMC - PubMed
-
- Myers AJ, Gibbs JR, Webster JA, Rohrer K, Zhao A, et al. A survey of genetic human cortical gene expression. Nat Genet. 2007;39:1494–1499. - PubMed
-
- Schadt EE, Molony C, Chudin E, Hao K, Yang X, et al. Mapping the genetic architecture of gene expression in human liver. PLoS Biol. 2008;6:e107. doi: 10.1371/journal.pbio.0060107. - DOI - PMC - PubMed
-
- Veyrieras JB, Kudaravalli S, Kim SY, Dermitzakis ET, Gilad Y, et al. High-resolution mapping of expression-QTLs yields insight into human gene regulation. PLoS Genet. 2008;4:e1000214. doi: 10.1371/journal.pgen.1000214. - DOI - PMC - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources