Epigenome-Wide Association Study for Parkinson's Disease

被引:57
作者
Moore, Kerry [1 ]
McKnight, Amy Jayne [1 ]
Craig, David [1 ]
O'Neill, Francis [1 ]
机构
[1] Queens Univ Belfast, Belfast, Antrim, North Ireland
关键词
Methylation; Parkinson's disease; Anxiety; Epigenetics; FANCC; TNKS2; DNA METHYLATION ANALYSIS; ANXIETY; EPIGENETICS; DYSFUNCTION; DISCOVERY; EXPOSURE; ONSET; DJ-1; GENE;
D O I
10.1007/s12017-014-8332-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
A methylation-based EWAS on carefully phenotyped individuals with Parkinson's disease (PD) was conducted to reveal prioritised genes and pathways with statistically significant and sizable changes in PD and in the anxiety that often accompanies it. This was followed by subsequent replication of top-ranked CpG sites. Using the Infinium(A (R)) HumanMethylation 450K beadchip (Illumina Inc., USA), twenty unique genes with a sizable difference in methylation (P (adjusted) < 0.05, Delta beta a parts per thousand yen 0.2), after correction for multiple testing, were identified between PD and controls, while seventeen were identified between PD with anxiety and PD without anxiety. Twelve top ranked, significantly associated loci in PD were evaluated in an independent replicate population using Sequenom EpiTYPER for 219 individuals with similar phenotypes to the cross-sectional case-control discovery design. FANCC cg14115740 and TNKS2 cg11963436 show significant differential methylation between PD cases and controls using both techniques and their Delta beta values, which have the same direction of effect, are reasonable to warrant further investigation.
引用
收藏
页码:845 / 855
页数:11
相关论文
共 58 条
[1]  
Almeida Maria do Rosario, 2012, Front Neurol, V3, P65, DOI 10.3389/fneur.2012.00065
[2]   UCH-L1 aggresome formation in response to proteasome impairment indicates a role in inclusion formation in Parkinson's disease [J].
Ardley, HC ;
Scott, GB ;
Rose, SA ;
Tan, NGS ;
Robinson, PA .
JOURNAL OF NEUROCHEMISTRY, 2004, 90 (02) :379-391
[3]   Parkinson's disease and cancer risk: a systematic review and meta-analysis [J].
Bajaj, Archna ;
Driver, Jane A. ;
Schernhammer, Eva S. .
CANCER CAUSES & CONTROL, 2010, 21 (05) :697-707
[4]   Double-strand RNA dependent protein kinase (PKR) is involved in the extrastriatal degeneration in Parkinson's disease and Huntington's disease [J].
Bando, Y ;
Onuki, R ;
Katayama, T ;
Manabe, T ;
Kudo, T ;
Taira, K ;
Tohyama, M .
NEUROCHEMISTRY INTERNATIONAL, 2005, 46 (01) :11-18
[5]   Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus [J].
Bell, Christopher G. ;
Teschendorff, Andrew E. ;
Rakyan, Vardhman K. ;
Maxwell, Alexander P. ;
Beck, Stephan ;
Savage, David A. .
BMC MEDICAL GENOMICS, 2010, 3
[6]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[7]   How far are we in understanding the cause of Parkinson's disease? [J].
BenShlomo, Y .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1996, 61 (01) :4-16
[8]   Tobacco-Smoking-Related Differential DNA Methylation: 27K Discovery and Replication [J].
Breitling, Lutz P. ;
Yang, Rongxi ;
Korn, Bernhard ;
Burwinkel, Barbara ;
Brenner, Hermann .
AMERICAN JOURNAL OF HUMAN GENETICS, 2011, 88 (04) :450-457
[9]   Parkin uses the UPS to ship off dysfunctional mitochondria [J].
Chan, Nickie C. ;
Chan, David C. .
AUTOPHAGY, 2011, 7 (07) :771-772
[10]   Maternal Genome-Wide DNA Methylation Patterns and Congenital Heart Defects [J].
Chowdhury, Shimul ;
Erickson, Stephen W. ;
MacLeod, Stewart L. ;
Cleves, Mario A. ;
Hu, Ping ;
Karim, Mohammad A. ;
Hobbs, Charlotte A. .
PLOS ONE, 2011, 6 (01)