Evidence for DNA methylation mediating genetic liability to non-syndromic cleft lip/palate

Laurence Howe; Thomas Richardson; Ryan Arathimos; Lucas Alvizi; Maria Rita Passos-Bueno; Philip Stanier; Ellen A Nohr; Kerstin Ludwig; Elisabeth Mangold; Michael Knapp; Evie Stergiakouli; Beate St Pourcain; George Davey Smith; Jonathan Sandy; Caroline Relton; Sarah Lewis; Gibran Hemani; Gemma Sharp

doi:10.2217/epi-2018-0091

Evidence for DNA methylation mediating genetic liability to non-syndromic cleft lip/palate

Laurence Howe, Thomas Richardson, Ryan Arathimos, Lucas Alvizi, Maria Rita Passos-Bueno, Philip Stanier, Ellen A Nohr, Kerstin Ludwig, Elisabeth Mangold, Michael Knapp, Evie Stergiakouli, Beate St Pourcain, George Davey Smith, Jonathan Sandy, Caroline Relton, Sarah Lewis, Gibran Hemani, Gemma Sharp^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

27 Citations (Scopus)

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Abstract

Aim: To determine if nonsyndromic cleft lip with or without cleft palate (nsCL/P) genetic risk variants influence liability to nsCL/P through gene regulation pathways, such as those involving DNA methylation. Materials & methods: nsCL/P genetic summary data and methylation data from four studies were used in conjunction with Mendelian randomization and joint likelihood mapping to investigate potential mediation of nsCL/P genetic variants. Results & conclusion: Evidence was found at VAX1 (10q25.3), LOC146880 (17q23.3) and NTN1 (17p13.1), that liability to nsCL/P and variation in DNA methylation might be driven by the same genetic variant, suggesting that genetic variation at these loci may increase liability to nsCL/P by influencing DNA methylation. Follow-up analyses using different tissues and gene expression data provided further insight into possible biological mechanisms.

Original language	English
Pages (from-to)	133-145
Number of pages	13
Journal	Epigenomics
Volume	11
Issue number	2
Early online date	14 Jan 2019
DOIs	https://doi.org/10.2217/epi-2018-0091
Publication status	Published - 1 Feb 2019

Keywords

ALSPAC
epigenetics
mendelian randomization
nsCL/P

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Howe, L., Richardson, T., Arathimos, R., Alvizi, L., Passos-Bueno, M. R., Stanier, P., Nohr, E. A., Ludwig, K., Mangold, E., Knapp, M., Stergiakouli, E., St Pourcain, B., Davey Smith, G., Sandy, J., Relton, C., Lewis, S., Hemani, G., & Sharp, G. (2019). Evidence for DNA methylation mediating genetic liability to non-syndromic cleft lip/palate. Epigenomics, 11(2), 133-145. https://doi.org/10.2217/epi-2018-0091

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title = "Evidence for DNA methylation mediating genetic liability to non-syndromic cleft lip/palate",

abstract = "Aim: To determine if nonsyndromic cleft lip with or without cleft palate (nsCL/P) genetic risk variants influence liability to nsCL/P through gene regulation pathways, such as those involving DNA methylation. Materials & methods: nsCL/P genetic summary data and methylation data from four studies were used in conjunction with Mendelian randomization and joint likelihood mapping to investigate potential mediation of nsCL/P genetic variants. Results & conclusion: Evidence was found at VAX1 (10q25.3), LOC146880 (17q23.3) and NTN1 (17p13.1), that liability to nsCL/P and variation in DNA methylation might be driven by the same genetic variant, suggesting that genetic variation at these loci may increase liability to nsCL/P by influencing DNA methylation. Follow-up analyses using different tissues and gene expression data provided further insight into possible biological mechanisms.",

keywords = "ALSPAC, epigenetics, mendelian randomization, nsCL/P",

author = "Laurence Howe and Thomas Richardson and Ryan Arathimos and Lucas Alvizi and Passos-Bueno, {Maria Rita} and Philip Stanier and Nohr, {Ellen A} and Kerstin Ludwig and Elisabeth Mangold and Michael Knapp and Evie Stergiakouli and {St Pourcain}, Beate and {Davey Smith}, George and Jonathan Sandy and Caroline Relton and Sarah Lewis and Gibran Hemani and Gemma Sharp",

year = "2019",

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doi = "10.2217/epi-2018-0091",

language = "English",

volume = "11",

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journal = "Epigenomics",

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number = "2",

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Howe, L, Richardson, T, Arathimos, R, Alvizi, L, Passos-Bueno, MR, Stanier, P, Nohr, EA, Ludwig, K, Mangold, E, Knapp, M, Stergiakouli, E , St Pourcain, B , Davey Smith, G, Sandy, J, Relton, C, Lewis, S , Hemani, G & Sharp, G 2019, 'Evidence for DNA methylation mediating genetic liability to non-syndromic cleft lip/palate', Epigenomics, vol. 11, no. 2, pp. 133-145. https://doi.org/10.2217/epi-2018-0091

TY - JOUR

T1 - Evidence for DNA methylation mediating genetic liability to non-syndromic cleft lip/palate

AU - Howe, Laurence

AU - Richardson, Thomas

AU - Arathimos, Ryan

AU - Alvizi, Lucas

AU - Passos-Bueno, Maria Rita

AU - Stanier, Philip

AU - Nohr, Ellen A

AU - Ludwig, Kerstin

AU - Mangold, Elisabeth

AU - Knapp, Michael

AU - Stergiakouli, Evie

AU - St Pourcain, Beate

AU - Davey Smith, George

AU - Sandy, Jonathan

AU - Relton, Caroline

AU - Lewis, Sarah

AU - Hemani, Gibran

AU - Sharp, Gemma

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Aim: To determine if nonsyndromic cleft lip with or without cleft palate (nsCL/P) genetic risk variants influence liability to nsCL/P through gene regulation pathways, such as those involving DNA methylation. Materials & methods: nsCL/P genetic summary data and methylation data from four studies were used in conjunction with Mendelian randomization and joint likelihood mapping to investigate potential mediation of nsCL/P genetic variants. Results & conclusion: Evidence was found at VAX1 (10q25.3), LOC146880 (17q23.3) and NTN1 (17p13.1), that liability to nsCL/P and variation in DNA methylation might be driven by the same genetic variant, suggesting that genetic variation at these loci may increase liability to nsCL/P by influencing DNA methylation. Follow-up analyses using different tissues and gene expression data provided further insight into possible biological mechanisms.

AB - Aim: To determine if nonsyndromic cleft lip with or without cleft palate (nsCL/P) genetic risk variants influence liability to nsCL/P through gene regulation pathways, such as those involving DNA methylation. Materials & methods: nsCL/P genetic summary data and methylation data from four studies were used in conjunction with Mendelian randomization and joint likelihood mapping to investigate potential mediation of nsCL/P genetic variants. Results & conclusion: Evidence was found at VAX1 (10q25.3), LOC146880 (17q23.3) and NTN1 (17p13.1), that liability to nsCL/P and variation in DNA methylation might be driven by the same genetic variant, suggesting that genetic variation at these loci may increase liability to nsCL/P by influencing DNA methylation. Follow-up analyses using different tissues and gene expression data provided further insight into possible biological mechanisms.

KW - ALSPAC

KW - epigenetics

KW - mendelian randomization

KW - nsCL/P

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U2 - 10.2217/epi-2018-0091

DO - 10.2217/epi-2018-0091

M3 - Article (Academic Journal)

C2 - 30638414

AN - SCOPUS:85061284293

SN - 1750-1911

VL - 11

SP - 133

EP - 145

JO - Epigenomics

JF - Epigenomics

IS - 2

ER -

Evidence for DNA methylation mediating genetic liability to non-syndromic cleft lip/palate

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Evidence for DNA methylation mediating genetic liability to non-syndromic cleft lip/palate

Abstract

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MRC UoB UNITE Unit - Programme 2

MRC UoB UNITE Unit - Programme 5

IEU Theme 2

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