06/09/2021 Biology Medicine
DOI: 10.1038/s41588-021-00923-x SemanticScholar ID: 237442640

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

J. Min, G. Hemani, E. Hannon, K. Dekkers, J. Castillo-Fernandez, R. Luijk, E. Carnero-Montoro, D. Lawson, K. Burrows, M. Suderman, A. Bretherick, T. Richardson, J. Klughammer, V. Iotchkova, G. Sharp, A. Al Khleifat, A. Shatunov, A. Iacoangeli, W. McArdle, K. Ho, Ashish Kumar, C. Su00f6derhu00e4ll, C. Soriano-Tu00e1rraga, E. Giralt-Steinhauer, N. Kazmi, D. Mason, A. McRae, D. Corcoran, K. Sugden, S. Kasela, A. Cardona, F. Day, G. Cugliari, C. Viberti, S. Guarrera, M. Lerro, Richa Gupta, S. Bollepalli, P. Mandaviya, Yanni Zeng, T. Clarke, R. Walker, V. Schmoll, D. Czamara, Carlos Ruiz-Arenas, F. Rezwan, R. Marioni, Tian Lin, Yvonne Awaloff, M. Germain, D. Au00efssi, R. Zwamborn, K. V. van Eijk, Annelot M. Dekker, J. van Dongen, J. Hottenga, G. Willemsen, Cheng-Jian Xu, G. Barturen, F. Catalu00e0-Moll, M. Kerick, Carol A. Wang, P. Melton, H. Elliott, Jean Shin, M. Bernard, I. Yet, M. Smart, T. Gorrie-stone, Chris E. Shaw, Ammar Al Chalabi, S. Ring, G. Pershagen, E. Mu00e9len, J. Jimu00e9nezu2010Conde, J. Roquer, D. Lawlor, John Wright, N. Martin, G. Montgomery, T. Moffitt, R. Poulton, T. Esko, L. Milani, A. Metspalu, J. Perry, K. Ong, N. Wareham, G. Matullo, C. Sacerdote, S. Panico, A. Caspi, L. Arseneault, F. Gagnon, M. Ollikainen, J. Kaprio, J. Felix, F. Rivadeneira, H. Tiemeier, Marinus H. van IJzendoorn, A. Uitterlinden, V. Jaddoe, C. Haley, A. McIntosh, K. Evans, A. Murray, K. Ru00e4ikku00f6nen, J. Lahti, E. Nohr, T. Su00f8rensen, T. Hansen, C. S. Morgen, E. Binder, S. Lucae, J. Gonzu00e1lez, M. Bustamante, J. Sunyer, J. Holloway, W. Karmaus, Hongmei Zhang, I. Deary, N. Wray, J. Starr, M. Beekman, D. van Heemst, P. Slagboom, P. Morange, D. Tru00e9gouu00ebt, J. Veldink, G. Davies, E. D. de Geus, D. Boomsma, J. Vonk, B. Brunekreef, G. Koppelman, M. Alarcu00f3nu2010Riquelme, Rae-Chi Huang, C. Pennell, J. V. van Meurs, M. Ikram, A. Hughes, T. Tillin, N. Chaturvedi, Z. Pausova, T. Paus, T. Spector, M. Kumari, L. Schalkwyk, P. Visscher, G. Davey Smith, C. Bock, Tom R. Gaunt, J. Bell, B. Heijmans, J. Mill, C. Relton

Publication Summary

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.

CAER Authors

Avatar Image for John Wright

Prof. John Wright

Bradford Institute for Health Research - Chief Investigator Born in Bradford

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