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

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Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation. / Min, Josine L.; Hemani, Gibran; Hannon, Eilis; Dekkers, Koen F.; Castillo-Fernandez, Juan; Luijk, René; Carnero-Montoro, Elena; Lawson, Daniel J.; Burrows, Kimberley; Suderman, Matthew; Bretherick, Andrew D.; Richardson, Tom G.; Klughammer, Johanna; Iotchkova, Valentina; Sharp, Gemma; Al Khleifat, Ahmad; Shatunov, Aleksey; Iacoangeli, Alfredo; McArdle, Wendy L.; Ho, Karen M.; Kumar, Ashish; Söderhäll, Cilla; Soriano-Tárraga, Carolina; Giralt-Steinhauer, Eva; Kazmi, Nabila; Mason, Dan; McRae, Allan F.; Corcoran, David L.; Sugden, Karen; Kasela, Silva; Cardona, Alexia; Day, Felix R.; Cugliari, Giovanni; Viberti, Clara; Guarrera, Simonetta; Lerro, Michael; Gupta, Richa; Bollepalli, Sailalitha; Mandaviya, Pooja; Zeng, Yanni; Clarke, Toni Kim; Walker, Rosie M.; Schmoll, Vanessa; Czamara, Darina; Ruiz-Arenas, Carlos; Elliott, Hannah R.; Nohr, Ellen A.; Sørensen, Thorkild I.A.; Hansen, Torben; Morgen, Camilla S.; BIOS Consortium.

In: Nature Genetics, Vol. 53, No. 9, 2021, p. 1311-1321.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Min, JL, Hemani, G, Hannon, E, Dekkers, KF, Castillo-Fernandez, J, Luijk, R, Carnero-Montoro, E, Lawson, DJ, Burrows, K, Suderman, M, Bretherick, AD, Richardson, TG, Klughammer, J, Iotchkova, V, Sharp, G, Al Khleifat, A, Shatunov, A, Iacoangeli, A, McArdle, WL, Ho, KM, Kumar, A, Söderhäll, C, Soriano-Tárraga, C, Giralt-Steinhauer, E, Kazmi, N, Mason, D, McRae, AF, Corcoran, DL, Sugden, K, Kasela, S, Cardona, A, Day, FR, Cugliari, G, Viberti, C, Guarrera, S, Lerro, M, Gupta, R, Bollepalli, S, Mandaviya, P, Zeng, Y, Clarke, TK, Walker, RM, Schmoll, V, Czamara, D, Ruiz-Arenas, C, Elliott, HR, Nohr, EA, Sørensen, TIA, Hansen, T, Morgen, CS & BIOS Consortium 2021, 'Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation', Nature Genetics, vol. 53, no. 9, pp. 1311-1321. https://doi.org/10.1038/s41588-021-00923-x

APA

Min, J. L., Hemani, G., Hannon, E., Dekkers, K. F., Castillo-Fernandez, J., Luijk, R., Carnero-Montoro, E., Lawson, D. J., Burrows, K., Suderman, M., Bretherick, A. D., Richardson, T. G., Klughammer, J., Iotchkova, V., Sharp, G., Al Khleifat, A., Shatunov, A., Iacoangeli, A., McArdle, W. L., ... BIOS Consortium (2021). Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation. Nature Genetics, 53(9), 1311-1321. https://doi.org/10.1038/s41588-021-00923-x

Vancouver

Min JL, Hemani G, Hannon E, Dekkers KF, Castillo-Fernandez J, Luijk R et al. Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation. Nature Genetics. 2021;53(9):1311-1321. https://doi.org/10.1038/s41588-021-00923-x

Author

Min, Josine L. ; Hemani, Gibran ; Hannon, Eilis ; Dekkers, Koen F. ; Castillo-Fernandez, Juan ; Luijk, René ; Carnero-Montoro, Elena ; Lawson, Daniel J. ; Burrows, Kimberley ; Suderman, Matthew ; Bretherick, Andrew D. ; Richardson, Tom G. ; Klughammer, Johanna ; Iotchkova, Valentina ; Sharp, Gemma ; Al Khleifat, Ahmad ; Shatunov, Aleksey ; Iacoangeli, Alfredo ; McArdle, Wendy L. ; Ho, Karen M. ; Kumar, Ashish ; Söderhäll, Cilla ; Soriano-Tárraga, Carolina ; Giralt-Steinhauer, Eva ; Kazmi, Nabila ; Mason, Dan ; McRae, Allan F. ; Corcoran, David L. ; Sugden, Karen ; Kasela, Silva ; Cardona, Alexia ; Day, Felix R. ; Cugliari, Giovanni ; Viberti, Clara ; Guarrera, Simonetta ; Lerro, Michael ; Gupta, Richa ; Bollepalli, Sailalitha ; Mandaviya, Pooja ; Zeng, Yanni ; Clarke, Toni Kim ; Walker, Rosie M. ; Schmoll, Vanessa ; Czamara, Darina ; Ruiz-Arenas, Carlos ; Elliott, Hannah R. ; Nohr, Ellen A. ; Sørensen, Thorkild I.A. ; Hansen, Torben ; Morgen, Camilla S. ; BIOS Consortium. / Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation. In: Nature Genetics. 2021 ; Vol. 53, No. 9. pp. 1311-1321.

Bibtex

@article{4612bbf5d8e041c5afa433435f634585,

title = "Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation",

abstract = "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.",

author = "Min, {Josine L.} and Gibran Hemani and Eilis Hannon and Dekkers, {Koen F.} and Juan Castillo-Fernandez and Ren{\'e} Luijk and Elena Carnero-Montoro and Lawson, {Daniel J.} and Kimberley Burrows and Matthew Suderman and Bretherick, {Andrew D.} and Richardson, {Tom G.} and Johanna Klughammer and Valentina Iotchkova and Gemma Sharp and {Al Khleifat}, Ahmad and Aleksey Shatunov and Alfredo Iacoangeli and McArdle, {Wendy L.} and Ho, {Karen M.} and Ashish Kumar and Cilla S{\"o}derh{\"a}ll and Carolina Soriano-T{\'a}rraga and Eva Giralt-Steinhauer and Nabila Kazmi and Dan Mason and McRae, {Allan F.} and Corcoran, {David L.} and Karen Sugden and Silva Kasela and Alexia Cardona and Day, {Felix R.} and Giovanni Cugliari and Clara Viberti and Simonetta Guarrera and Michael Lerro and Richa Gupta and Sailalitha Bollepalli and Pooja Mandaviya and Yanni Zeng and Clarke, {Toni Kim} and Walker, {Rosie M.} and Vanessa Schmoll and Darina Czamara and Carlos Ruiz-Arenas and Elliott, {Hannah R.} and Nohr, {Ellen A.} and S{\o}rensen, {Thorkild I.A.} and Torben Hansen and Morgen, {Camilla S.} and {BIOS Consortium}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2021",

doi = "10.1038/s41588-021-00923-x",

language = "English",

volume = "53",

pages = "1311--1321",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "nature publishing group",

number = "9",

}

RIS

TY - JOUR

T1 - Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation

AU - Min, Josine L.

AU - Hemani, Gibran

AU - Hannon, Eilis

AU - Dekkers, Koen F.

AU - Castillo-Fernandez, Juan

AU - Luijk, René

AU - Carnero-Montoro, Elena

AU - Lawson, Daniel J.

AU - Burrows, Kimberley

AU - Suderman, Matthew

AU - Bretherick, Andrew D.

AU - Richardson, Tom G.

AU - Klughammer, Johanna

AU - Iotchkova, Valentina

AU - Sharp, Gemma

AU - Al Khleifat, Ahmad

AU - Shatunov, Aleksey

AU - Iacoangeli, Alfredo

AU - McArdle, Wendy L.

AU - Ho, Karen M.

AU - Kumar, Ashish

AU - Söderhäll, Cilla

AU - Soriano-Tárraga, Carolina

AU - Giralt-Steinhauer, Eva

AU - Kazmi, Nabila

AU - Mason, Dan

AU - McRae, Allan F.

AU - Corcoran, David L.

AU - Sugden, Karen

AU - Kasela, Silva

AU - Cardona, Alexia

AU - Day, Felix R.

AU - Cugliari, Giovanni

AU - Viberti, Clara

AU - Guarrera, Simonetta

AU - Lerro, Michael

AU - Gupta, Richa

AU - Bollepalli, Sailalitha

AU - Mandaviya, Pooja

AU - Zeng, Yanni

AU - Clarke, Toni Kim

AU - Walker, Rosie M.

AU - Schmoll, Vanessa

AU - Czamara, Darina

AU - Ruiz-Arenas, Carlos

AU - Elliott, Hannah R.

AU - Nohr, Ellen A.

AU - Sørensen, Thorkild I.A.

AU - Hansen, Torben

AU - Morgen, Camilla S.

AU - BIOS Consortium

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1038/s41588-021-00923-x

DO - 10.1038/s41588-021-00923-x

M3 - Journal article

C2 - 34493871

AN - SCOPUS:85103124472

VL - 53

SP - 1311

EP - 1321

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 9

ER -

ID: 280232365

Department of Public Health