Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain.

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 expr...

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Autores principales:	J Raphael Gibbs, Marcel P van der Brug, Dena G Hernandez, Bryan J Traynor, Michael A Nalls, Shiao-Lin Lai, Sampath Arepalli, Allissa Dillman, Ian P Rafferty, Juan Troncoso, Robert Johnson, H Ronald Zielke, Luigi Ferrucci, Dan L Longo, Mark R Cookson, Andrew B Singleton
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/2c6bddb840f5434bb40322ece5b8e839
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spelling	oai:doaj.org-article:2c6bddb840f5434bb40322ece5b8e8392021-12-02T20:03:42ZAbundant quantitative trait loci exist for DNA methylation and gene expression in human brain.1553-73901553-740410.1371/journal.pgen.1000952https://doaj.org/article/2c6bddb840f5434bb40322ece5b8e8392010-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20485568/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404A 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.J Raphael GibbsMarcel P van der BrugDena G HernandezBryan J TraynorMichael A NallsShiao-Lin LaiSampath ArepalliAllissa DillmanIan P RaffertyJuan TroncosoRobert JohnsonH Ronald ZielkeLuigi FerrucciDan L LongoMark R CooksonAndrew B SingletonPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 6, Iss 5, p e1000952 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 J Raphael Gibbs Marcel P van der Brug Dena G Hernandez Bryan J Traynor Michael A Nalls Shiao-Lin Lai Sampath Arepalli Allissa Dillman Ian P Rafferty Juan Troncoso Robert Johnson H Ronald Zielke Luigi Ferrucci Dan L Longo Mark R Cookson Andrew B Singleton Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain.
description	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.
format	article
author	J Raphael Gibbs Marcel P van der Brug Dena G Hernandez Bryan J Traynor Michael A Nalls Shiao-Lin Lai Sampath Arepalli Allissa Dillman Ian P Rafferty Juan Troncoso Robert Johnson H Ronald Zielke Luigi Ferrucci Dan L Longo Mark R Cookson Andrew B Singleton
author_facet	J Raphael Gibbs Marcel P van der Brug Dena G Hernandez Bryan J Traynor Michael A Nalls Shiao-Lin Lai Sampath Arepalli Allissa Dillman Ian P Rafferty Juan Troncoso Robert Johnson H Ronald Zielke Luigi Ferrucci Dan L Longo Mark R Cookson Andrew B Singleton
author_sort	J Raphael Gibbs
title	Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain.
title_short	Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain.
title_full	Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain.
title_fullStr	Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain.
title_full_unstemmed	Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain.
title_sort	abundant quantitative trait loci exist for dna methylation and gene expression in human brain.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/2c6bddb840f5434bb40322ece5b8e839
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Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain.

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