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

被引：23

作者：

Howe, Laurence J. ^{[1
,2
]}

Richardson, Tom G. ^{[1
]}

Arathimos, Ryan ^{[1
]}

Alvizi, Lucas ^{[3
]}

Passos-Bueno, Maria R.

Stanier, Philip ^{[4
]}

Nohr, Ellen ^{[5
]}

Ludwig, Kerstin U. ^{[6
,7
]}

Mangold, Elisabeth ^{[6
]}

Knapp, Michael ^{[8
]}

Stergiakouli, Evie ^{[1
]}

St Pourcain, Beate ^{[1
,9
,10
]}

Smith, George Davey ^{[1
]}

Sandy, Jonathan ^{[11
]}

Relton, Caroline L. ^{[1
]}

Lewis, Sarah J. ^{[1
,11
]}

Hemani, Gibran ^{[1
]}

Sharp, Gemma C. ^{[1
,11
]}

机构：

[1] Univ Bristol, MRC Integrat Epidemiol Unit, Populat Hlth Sci, Bristol BS8 2BN, Avon, England

[2] UCL, Inst Cardiovasc Sci, London NW1 2DA, England

[3] Univ Sao Paulo, Inst Biociencias, Ctr Pesquisas Genoma Humano & Celulas Tronco, Sao Paulo, Brazil

[4] UCL, UCL Great Ormond St Inst Child Hlth, Genet & Genom Med, London WC1N 3JH, England

[5] Aarhus Univ, Inst Publ Hlth, Aarhus, Denmark

[6] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany

[7] Univ Bonn, Dept Genom, Life & Brain Ctr, D-53127 Bonn, Germany

[8] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-53127 Bonn, Germany

[9] Max Planck Inst Psycholinguist, NL-6525 XD Nijmegen, Netherlands

[10] Donders Inst, NL-6525 EN Nijmegen, Netherlands

[11] Univ Bristol, Bristol Dent Sch, Bristol BS8 2BN, Avon, England

来源：

EPIGENOMICS | 2019年 / 11卷 / 02期

基金：

英国生物技术与生命科学研究理事会;

关键词：

ALSPAC; epigenetics; mendelian randomization; nsCL/P; GENOME-WIDE METAANALYSES; MENDELIAN RANDOMIZATION; SUSCEPTIBILITY LOCUS; LIP; PALATE; ASSOCIATION; VARIANTS; RISK; EXPRESSION; EPIDEMIOLOGY;

D O I：

10.2217/epi-2018-0091

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：133 / 145

页数：13

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