Co-occurring expression and methylation QTLs allow detection of common causal variants and shared biological mechanisms

Nature Communications
Brandon L PierceHabibul Ahsan

Abstract

Inherited genetic variation affects local gene expression and DNA methylation in humans. Most expression quantitative trait loci (cis-eQTLs) occur at the same genomic location as a methylation QTL (cis-meQTL), suggesting a common causal variant and shared mechanism. Using DNA and RNA from peripheral blood of Bangladeshi individuals, here we use co-localization methods to identify eQTL-meQTL pairs likely to share a causal variant. We use partial correlation and mediation analyses to identify >400 of these pairs showing evidence of a causal relationship between expression and methylation (i.e., shared mechanism) with many additional pairs we are underpowered to detect. These co-localized pairs are enriched for SNPs showing opposite associations with expression and methylation, although many SNPs affect multiple CpGs in opposite directions. This work demonstrates the pervasiveness of co-regulated expression and methylation in the human genome. Applying this approach to other types of molecular QTLs can enhance our understanding of regulatory mechanisms.

References

Apr 25, 2006·Biostatistics·W Evan JohnsonAriel Rabinovic
Nov 9, 2010·Genetic Epidemiology·Yun LiGonçalo R Abecasis
Feb 7, 2012·Nature·Jacob F DegnerJonathan K Pritchard
Apr 12, 2012·Bioinformatics·Andrey A Shabalin
May 19, 2012·Human Molecular Genetics·Anbarasu LourdusamyUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Mar 15, 2013·Proceedings of the National Academy of Sciences of the United States of America·Åsa JohanssonUlf Gyllensten
Apr 18, 2013·European Journal of Clinical Investigation·Maria ArgosHabibul Ahsan
Jun 12, 2013·ELife·Maria Gutierrez-ArcelusEmmanouil T Dermitzakis
Sep 11, 2013·International Journal of Epidemiology·Lorenzo RichiardiDaniela Zugna
Oct 19, 2013·Science·Graham McVickerJonathan K Pritchard
Jan 7, 2014·Nature·Yukinori OkadaRobert M Plenge
Mar 25, 2014·American Journal of Human Genetics·Yun LiuAndrew P Feinberg
Aug 21, 2014·Nature Communications·Jean MonlongRoderic Guigó
Jan 9, 2015·PLoS Genetics·Athma A PaiYoav Gilad
Feb 3, 2015·Nature Genetics·Brendan K Bulik-SullivanBenjamin M Neale
Feb 25, 2015·Nature Reviews. Genetics·Frank W Albert, Leonid Kruglyak
Apr 30, 2016·Science·Yang I LiJonathan K Pritchard
May 18, 2016·Nature Genetics·Joseph K PickrellDavid A Hinds
Aug 2, 2016·Nature Reviews. Genetics·Heng ZhuJiang Qian
Nov 22, 2016·American Journal of Human Genetics·Farhad HormozdiariEleazar Eskin
Oct 13, 2017·Nature·UNKNOWN GTEx ConsortiumStephen B Montgomery

❮ Previous
Next ❯

Citations

Nov 20, 2018·PLoS Genetics·Fabien DelahayeFrancine Hughes
Jun 13, 2019·Nature Communications·Darina CzamaraElisabeth B Binder
Jul 3, 2020·Journal of Internal Medicine·L Kular, M Jagodic
Dec 20, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Louis GauthierStephen W Michnick
Mar 7, 2019·Frontiers in Pharmacology·Emma CazalyJing Tang
Apr 1, 2020·PLoS Genetics·James Y DaiJanet L Stanford
Nov 29, 2020·Pigment Cell & Melanoma Research·Carolina BonillaHannah R Elliott
Jan 13, 2021·Nature Reviews. Genetics·Luisa PereiraMichèle Ramsay
Jan 17, 2020·The Journal of Allergy and Clinical Immunology·Alexander D ClarkLouise N Reynard
Apr 16, 2020·Trends in Genetics : TIG·Youqiong YeLeng Han
Mar 9, 2021·PLoS Genetics·Arjun BhattacharyaMichael I Love
May 2, 2021·Genome Biology·Sergio Villicaña, Jordana T Bell
Jun 26, 2021·European Respiratory Review : an Official Journal of the European Respiratory Society·Iain R KonigsbergIvana V Yang
Aug 21, 2021·Briefings in Bioinformatics·Chen LyuMing Li

❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping
chip

Software Mentioned

qvalue
BeadStudio
FastQTL
R
ComBat
coloc
coloc R
MaCH
BNA
BEST

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.