Parent of origin genetic effects on methylation in humans are common and influence complex trait variation

Yanni Zeng; Carmen Amador; Charley Xia; Riccardo Marioni; Duncan Sproul; Rosie M. Walker; Stewart W Morris; Andrew Bretherick; Oriol Canela-Xandri; Thibaud S. Boutin; David W. Clark; Archie Campbell; Konrad Rawlik; Caroline Hayward; Reka Nagy; Albert Tenesa; David J. Porteous; James F. Wilson; Ian J. Deary; Kathryn L. Evans; Andrew M. McIntosh; Pau Navarro; Chris S. Haley

doi:10.1038/s41467-019-09301-y

Parent of origin genetic effects on methylation in humans are common and influence complex trait variation

Yanni Zeng, Carmen Amador, Charley Xia, Riccardo Marioni, Duncan Sproul, Rosie M. Walker, Stewart W Morris, Andrew Bretherick, Oriol Canela-Xandri, Thibaud S. Boutin, David W. Clark, Archie Campbell, Konrad Rawlik, Caroline Hayward, Reka Nagy, Albert Tenesa, David J. Porteous, James F. Wilson, Ian J. Deary, Kathryn L. EvansAndrew M. McIntosh, Pau Navarro, Chris S. Haley

Research output: Contribution to journal › Article › peer-review

Abstract

Parent-of-origin effects (POE) exist when there is differential expression of alleles inherited from the two parents. A genome-wide scan for POE on DNA methylation at 639,238 CpGs in 5,101 individuals identifies 733 independent methylation CpGs potentially influenced by POE at a false discovery rate ≤ 0.05 of which 331 had not previously been identified. Cis and trans methylation quantitative trait loci (mQTL) regulate methylation variation through POE at 54% (399/733) of the identified POE-influenced CpGs. The combined results provide strong evidence for previously unidentified POE-influenced CpGs at 171 independent loci. Methylation variation at 14 of the POE-influenced CpGs is associated with multiple metabolic traits. A phenome-wide association analysis using the POE mQTL SNPs identifies a previously unidentified imprinted locus associated with waist circumference. These results provide a high resolution population-level map for POE on DNA methylation sites, their local and distant regulators and potential consequences for complex traits.

Original language	English
Article number	1383
Number of pages	13
Journal	Nature Communications
Volume	10
DOIs	https://doi.org/10.1038/s41467-019-09301-y
Publication status	Published - 27 Mar 2019

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ZengEatlNC2019ParentOfOriginGeneticEffectFinal published version, 1.58 MBLicence: Creative Commons: Attribution (CC-BY)

2 Finished

Stratifying Resilience and Depression Longitudinally
McIntosh, A., Deary, I., Evans, K., Haley, C. & Porteous, D.
UK-based charities
1/01/15 → 30/06/21
Project: Research
RA2662 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2.
Porteous, D.
1/09/13 → 31/08/19
Project: Research

1 Article

Publisher Correction: Parent of origin genetic effects on methylation in humans are common and influence complex trait variation
Zeng, Y., Amador, C., Xia, C., Marioni, R., Sproul, D., Walker, R. M., Morris, S. W., Bretherick, A., Canela-Xandri, O., Boutin, T. S., Clark, D. W., Campbell, A., Rawlik, K., Hayward, C., Nagy, R., Tenesa, A., Porteous, D. J., Wilson, J. F., Deary, I. J., Evans, K. L., & 3 othersMcIntosh, A. M., Navarro, P. & Haley, C. S., 1 May 2019, In: Nature Communications. 10, 1, p. 2069
Research output: Contribution to journal › Article › peer-review

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Chris Haley
- Deanery of Molecular, Genetic and Population Health Sciences - Visitor: Default Visitor
Person: Affiliated Independent Researcher
Andrew McIntosh
- Deanery of Clinical Sciences - Chair of Biological Psychiatry
- Centre for Clinical Brain Sciences
- Edinburgh Neuroscience
Person: Academic: Research Active

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Zeng, Y., Amador, C., Xia, C., Marioni, R., Sproul, D., Walker, R. M., Morris, S. W., Bretherick, A., Canela-Xandri, O., Boutin, T. S., Clark, D. W., Campbell, A., Rawlik, K., Hayward, C., Nagy, R., Tenesa, A., Porteous, D. J., Wilson, J. F., Deary, I. J., ... Haley, C. S. (2019). Parent of origin genetic effects on methylation in humans are common and influence complex trait variation. Nature Communications, 10, Article 1383. https://doi.org/10.1038/s41467-019-09301-y

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title = "Parent of origin genetic effects on methylation in humans are common and influence complex trait variation",

abstract = "Parent-of-origin effects (POE) exist when there is differential expression of alleles inherited from the two parents. A genome-wide scan for POE on DNA methylation at 639,238 CpGs in 5,101 individuals identifies 733 independent methylation CpGs potentially influenced by POE at a false discovery rate ≤ 0.05 of which 331 had not previously been identified. Cis and trans methylation quantitative trait loci (mQTL) regulate methylation variation through POE at 54% (399/733) of the identified POE-influenced CpGs. The combined results provide strong evidence for previously unidentified POE-influenced CpGs at 171 independent loci. Methylation variation at 14 of the POE-influenced CpGs is associated with multiple metabolic traits. A phenome-wide association analysis using the POE mQTL SNPs identifies a previously unidentified imprinted locus associated with waist circumference. These results provide a high resolution population-level map for POE on DNA methylation sites, their local and distant regulators and potential consequences for complex traits.",

author = "Yanni Zeng and Carmen Amador and Charley Xia and Riccardo Marioni and Duncan Sproul and Walker, {Rosie M.} and Morris, {Stewart W} and Andrew Bretherick and Oriol Canela-Xandri and Boutin, {Thibaud S.} and Clark, {David W.} and Archie Campbell and Konrad Rawlik and Caroline Hayward and Reka Nagy and Albert Tenesa and Porteous, {David J.} and Wilson, {James F.} and Deary, {Ian J.} and Evans, {Kathryn L.} and McIntosh, {Andrew M.} and Pau Navarro and Haley, {Chris S.}",

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doi = "10.1038/s41467-019-09301-y",

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Zeng, Y, Amador, C, Xia, C, Marioni, R , Sproul, D, Walker, RM, Morris, SW, Bretherick, A , Canela-Xandri, O , Boutin, TS, Clark, DW, Campbell, A , Rawlik, K , Hayward, C, Nagy, R, Tenesa, A, Porteous, DJ, Wilson, JF , Deary, IJ , Evans, KL , McIntosh, AM , Navarro, P & Haley, CS 2019, 'Parent of origin genetic effects on methylation in humans are common and influence complex trait variation', Nature Communications, vol. 10, 1383. https://doi.org/10.1038/s41467-019-09301-y

TY - JOUR

T1 - Parent of origin genetic effects on methylation in humans are common and influence complex trait variation

AU - Zeng, Yanni

AU - Amador, Carmen

AU - Xia, Charley

AU - Marioni, Riccardo

AU - Sproul, Duncan

AU - Walker, Rosie M.

AU - Morris, Stewart W

AU - Bretherick, Andrew

AU - Canela-Xandri, Oriol

AU - Boutin, Thibaud S.

AU - Clark, David W.

AU - Campbell, Archie

AU - Rawlik, Konrad

AU - Hayward, Caroline

AU - Nagy, Reka

AU - Tenesa, Albert

AU - Porteous, David J.

AU - Wilson, James F.

AU - Deary, Ian J.

AU - Evans, Kathryn L.

AU - McIntosh, Andrew M.

AU - Navarro, Pau

AU - Haley, Chris S.

N1 - Will be published open

PY - 2019/3/27

Y1 - 2019/3/27

N2 - Parent-of-origin effects (POE) exist when there is differential expression of alleles inherited from the two parents. A genome-wide scan for POE on DNA methylation at 639,238 CpGs in 5,101 individuals identifies 733 independent methylation CpGs potentially influenced by POE at a false discovery rate ≤ 0.05 of which 331 had not previously been identified. Cis and trans methylation quantitative trait loci (mQTL) regulate methylation variation through POE at 54% (399/733) of the identified POE-influenced CpGs. The combined results provide strong evidence for previously unidentified POE-influenced CpGs at 171 independent loci. Methylation variation at 14 of the POE-influenced CpGs is associated with multiple metabolic traits. A phenome-wide association analysis using the POE mQTL SNPs identifies a previously unidentified imprinted locus associated with waist circumference. These results provide a high resolution population-level map for POE on DNA methylation sites, their local and distant regulators and potential consequences for complex traits.

AB - Parent-of-origin effects (POE) exist when there is differential expression of alleles inherited from the two parents. A genome-wide scan for POE on DNA methylation at 639,238 CpGs in 5,101 individuals identifies 733 independent methylation CpGs potentially influenced by POE at a false discovery rate ≤ 0.05 of which 331 had not previously been identified. Cis and trans methylation quantitative trait loci (mQTL) regulate methylation variation through POE at 54% (399/733) of the identified POE-influenced CpGs. The combined results provide strong evidence for previously unidentified POE-influenced CpGs at 171 independent loci. Methylation variation at 14 of the POE-influenced CpGs is associated with multiple metabolic traits. A phenome-wide association analysis using the POE mQTL SNPs identifies a previously unidentified imprinted locus associated with waist circumference. These results provide a high resolution population-level map for POE on DNA methylation sites, their local and distant regulators and potential consequences for complex traits.

U2 - 10.1038/s41467-019-09301-y

DO - 10.1038/s41467-019-09301-y

M3 - Article

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

M1 - 1383

ER -

Parent of origin genetic effects on methylation in humans are common and influence complex trait variation

Abstract

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Stratifying Resilience and Depression Longitudinally

RA2662 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2.

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Publisher Correction: Parent of origin genetic effects on methylation in humans are common and influence complex trait variation

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Chris Haley

Andrew McIntosh

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