Genome-wide DNA methylation profiling in whole blood reveals epigenetic signatures associated with migraine

被引:39
作者
Gerring, Zachary F. [1 ]
McRae, Allan F. [2 ,3 ]
Montgomery, Grant W. [2 ]
Nyholt, Dale R. [1 ]
机构
[1] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Stat & Genom Epidemiol Lab, Brisbane, Qld, Australia
[2] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia
[3] Univ Queensland, Queensland Brain Inst, Ctr Neurogenet & Stat Genom, Brisbane, Qld, Australia
基金
英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;
关键词
Migraine; Differential; Methylation; Blood; GENETIC-FACTOR; PREVALENCE; DISEASE; BURDEN; RISK; AURA; CARE;
D O I
10.1186/s12864-018-4450-2
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Migraine is a common heritable neurovascular disorder typically characterised by episodic attacks of severe pulsating headache and nausea, often accompanied by visual, auditory or other sensory symptoms. Although genome-wide association studies have identified over 40 single nucleotide polymorphisms associated with migraine, there remains uncertainty about the casual genes involved in disease pathogenesis and how their function is regulated. Results: We performed an epigenome-wide association study, quantifying genome-wide patterns of DNA methylation in 67 migraine cases and 67 controls with a matching age and sex distribution. Association analyses between migraine and methylation probe expression, after adjustment for cell type proportions, indicated an excess of small P values, but there was no significant single-probe association after correction for multiple testing (P < 1.09 x 10(-7)). However, utilising a 1 kb sliding window approach to combine adjacent migraine-methylation association P values, we identified 62 independent differentially methylated regions (DMRs) underlying migraine (false discovery rate < 0.05). Migraine association signals were subtle but consistent in effect direction across the length of each DMR. Subsequent analyses showed that the migraine-associated DMRs were enriched in regulatory elements of the genome and were in close proximity to genes involved in solute transportation and haemostasis. Conclusions: This study represents the first genome-wide analysis of DNA methylation in migraine. We have identified DNA methylation in the whole blood of subjects associated with migraine, highlighting novel loci that provide insight into the biological pathways and mechanisms underlying migraine pathogenesis.
引用
收藏
页数:10
相关论文
共 61 条
[1]   The role of regulatory variation in complex traits and disease [J].
Albert, Frank W. ;
Kruglyak, Leonid .
NATURE REVIEWS GENETICS, 2015, 16 (04) :197-212
[2]   DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines [J].
Bell, Jordana T. ;
Pai, Athma A. ;
Pickrell, Joseph K. ;
Gaffney, Daniel J. ;
Pique-Regi, Roger ;
Degner, Jacob F. ;
Gilad, Yoav ;
Pritchard, Jonathan K. .
GENOME BIOLOGY, 2011, 12 (01)
[3]   Perceptions of epigenetics [J].
Bird, Adrian .
NATURE, 2007, 447 (7143) :396-398
[4]   Epigenome-wide Association Studies and the Interpretation of Disease -Omics [J].
Birney, Ewan ;
Smith, George Davey ;
Greally, John M. .
PLOS GENETICS, 2016, 12 (06)
[5]   Analysing and interpreting DNA methylation data [J].
Bock, Christoph .
NATURE REVIEWS GENETICS, 2012, 13 (10) :705-719
[6]   Diagnostic Accuracy of the ID Migraine: A Systematic Review and Meta-Analysis [J].
Cousins, Grainne ;
Hijazze, Samira ;
Van de Laar, Floris A. ;
Fahey, Tom .
HEADACHE, 2011, 51 (07) :1140-1148
[7]   Migraine aura pathophysiology: the role of blood vessels and microembolisation [J].
Dalkara, Turgay ;
Nozari, Ala ;
Moskowitz, Michael A. .
LANCET NEUROLOGY, 2010, 9 (03) :309-317
[8]   Facilitative glucose transporter 9, a unique hexose and urate transporter [J].
Doblado, Manuel ;
Moley, Kelle H. .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2009, 297 (04) :E831-E835
[9]   An integrated encyclopedia of DNA elements in the human genome [J].
Dunham, Ian ;
Kundaje, Anshul ;
Aldred, Shelley F. ;
Collins, Patrick J. ;
Davis, CarrieA. ;
Doyle, Francis ;
Epstein, Charles B. ;
Frietze, Seth ;
Harrow, Jennifer ;
Kaul, Rajinder ;
Khatun, Jainab ;
Lajoie, Bryan R. ;
Landt, Stephen G. ;
Lee, Bum-Kyu ;
Pauli, Florencia ;
Rosenbloom, Kate R. ;
Sabo, Peter ;
Safi, Alexias ;
Sanyal, Amartya ;
Shoresh, Noam ;
Simon, Jeremy M. ;
Song, Lingyun ;
Trinklein, Nathan D. ;
Altshuler, Robert C. ;
Birney, Ewan ;
Brown, James B. ;
Cheng, Chao ;
Djebali, Sarah ;
Dong, Xianjun ;
Dunham, Ian ;
Ernst, Jason ;
Furey, Terrence S. ;
Gerstein, Mark ;
Giardine, Belinda ;
Greven, Melissa ;
Hardison, Ross C. ;
Harris, Robert S. ;
Herrero, Javier ;
Hoffman, Michael M. ;
Iyer, Sowmya ;
Kellis, Manolis ;
Khatun, Jainab ;
Kheradpour, Pouya ;
Kundaje, Anshul ;
Lassmann, Timo ;
Li, Qunhua ;
Lin, Xinying ;
Marinov, Georgi K. ;
Merkel, Angelika ;
Mortazavi, Ali .
NATURE, 2012, 489 (7414) :57-74
[10]   DNA methylation profiling of human chromosomes 6, 20 and 22 [J].
Eckhardt, Florian ;
Lewin, Joern ;
Cortese, Rene ;
Rakyan, Vardhman K. ;
Attwood, John ;
Burger, Matthias ;
Burton, John ;
Cox, Tony V. ;
Davies, Rob ;
Down, Thomas A. ;
Haefliger, Carolina ;
Horton, Roger ;
Howe, Kevin ;
Jackson, David K. ;
Kunde, Jan ;
Koenig, Christoph ;
Liddle, Jennifer ;
Niblett, David ;
Otto, Thomas ;
Pettett, Roger ;
Seemann, Stefanie ;
Thompson, Christian ;
West, Tony ;
Rogers, Jane ;
Olek, Alex ;
Berlin, Kurt ;
Beck, Stephan .
NATURE GENETICS, 2006, 38 (12) :1378-1385