Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis.

Abstract:

:Epigenetic mechanisms integrate genetic and environmental causes of disease, but comprehensive genome-wide analyses of epigenetic modifications have not yet demonstrated robust association with common diseases. Using Illumina HumanMethylation450 arrays on 354 anti-citrullinated protein antibody-associated rheumatoid arthritis cases and 337 controls, we identified two clusters within the major histocompatibility complex (MHC) region whose differential methylation potentially mediates genetic risk for rheumatoid arthritis. To reduce confounding factors that have hampered previous epigenome-wide studies, we corrected for cellular heterogeneity by estimating and adjusting for cell-type proportions in our blood-derived DNA samples and used mediation analysis to filter out associations likely to be a consequence of disease. Four CpGs also showed an association between genotype and variance of methylation. The associations for both clusters replicated at least one CpG (P < 0.01), with the rest showing suggestive association, in monocyte cell fractions in an independent cohort of 12 cases and 12 controls. Thus, DNA methylation is a potential mediator of genetic risk.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Liu Y,Aryee MJ,Padyukov L,Fallin MD,Hesselberg E,Runarsson A,Reinius L,Acevedo N,Taub M,Ronninger M,Shchetynsky K,Scheynius A,Kere J,Alfredsson L,Klareskog L,Ekström TJ,Feinberg AP

doi

10.1038/nbt.2487

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

142-7

issue

2

eissn

1087-0156

issn

1546-1696

pii

nbt.2487

journal_volume

31

pub_type

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