Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation

BIOS Consortium, Josine L. Min*, Gibran Hemani, Eilis Hannon, Koen F. Dekkers, Juan Castillo-Fernandez, René Luijk, Elena Carnero-Montoro, Daniel J. Lawson, Kimberley Burrows, Matthew Suderman, Andrew D. Bretherick, Tom G. Richardson, Johanna Klughammer, Valentina Iotchkova, Gemma Sharp, Ahmad Al Khleifat, Aleksey Shatunov, Alfredo Iacoangeli, Wendy L. McArdleKaren M. Ho, Ashish Kumar, Cilla Söderhäll, Carolina Soriano-Tárraga, Eva Giralt-Steinhauer, Nabila Kazmi, Dan Mason, Allan F. McRae, David L. Corcoran, Karen Sugden, Silva Kasela, Alexia Cardona, Felix R. Day, Giovanni Cugliari, Clara Viberti, Simonetta Guarrera, Michael Lerro, Richa Gupta, Sailalitha Bollepalli, Pooja Mandaviya, Yanni Zeng, Toni Kim Clarke, Rosie M. Walker, Vanessa Schmoll, Idil Yet, Ammar Al Chalabi, Avshalom Caspi, Louise Arseneault, Timothy D. Spector, Leonard C. Schalkwyk, Jordana T. Bell

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

156 Citations (Scopus)


Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15–17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype–phenotype map than previously anticipated.

Original languageEnglish
Pages (from-to)1311-1321
Number of pages11
JournalNature Genetics
Issue number9
Publication statusPublished - Sept 2021


Dive into the research topics of 'Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation'. Together they form a unique fingerprint.

Cite this