University of Surrey

Test tubes in the lab Research in the ATI Dance Research

Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants

Allum, F, Shao, X, Guénard, F, Simon, MM, Busche, S, Caron, M, Lambourne, J, Lessard, J, Tandre, K, Hedman, ÅK , Kwan, T, Ge, B, Rönnblom, L, McCarthy, MI, Deloukas, P, Richmond, T, Burgess, D, Spector, TD, Tchernof, A, Marceau, S, Lathrop, M, Vohl, MC, Pastinen, T, Grundberg, E, Ahmadi, KR, Ainali, C, Barrett, A, Bataille, V, Bell, JT, Buil, A, Dermitzakis, ET, Dimas, AS, Durbin, R, Glass, D, Hassanali, N, Ingle, C, Knowles, D, Krestyaninova, M, Lindgren, CM, Lowe, CE, Meduri, E, Di Meglio, P, Min, JL, Montgomery, SB, Nestle, FO, Nica, AC, Nisbet, J, O'Rahilly, S, Parts, L, Potter, S, Sandling, J, Sekowska, M, Shin, SY, Small, KS, Soranzo, N, Surdulescu, G, Travers, ME, Tsaprouni, L, Tsoka, S, Wilk, A, Yang, TP and Zondervan, KT (2015) Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants Nature Communications, 6.

Full text not available from this repository.

Abstract

© 2015 Macmillan Publishers Limited. All rights reserved.Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequencing functional methylomes, while simultaneously providing genetic variation information. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adipose tissue (AT) samples and public databases to design AT-specific panels. We establish its efficiency for high-density interrogation of methylome variability by systematic comparisons with other approaches and demonstrate its applicability by identifying novel methylation variation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol, including at CD36. Our more comprehensive AT panel assesses tissue methylation and genotypes in parallel at ∼4 and ∼3M sites, respectively. Our study demonstrates that MCC-Seq provides comparable accuracy to alternative approaches but enables more efficient cataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS.

Item Type: Article
Authors :
NameEmailORCID
Allum, FUNSPECIFIEDUNSPECIFIED
Shao, XUNSPECIFIEDUNSPECIFIED
Guénard, FUNSPECIFIEDUNSPECIFIED
Simon, MMUNSPECIFIEDUNSPECIFIED
Busche, SUNSPECIFIEDUNSPECIFIED
Caron, MUNSPECIFIEDUNSPECIFIED
Lambourne, JUNSPECIFIEDUNSPECIFIED
Lessard, JUNSPECIFIEDUNSPECIFIED
Tandre, KUNSPECIFIEDUNSPECIFIED
Hedman, ÅKUNSPECIFIEDUNSPECIFIED
Kwan, TUNSPECIFIEDUNSPECIFIED
Ge, BUNSPECIFIEDUNSPECIFIED
Rönnblom, LUNSPECIFIEDUNSPECIFIED
McCarthy, MIUNSPECIFIEDUNSPECIFIED
Deloukas, PUNSPECIFIEDUNSPECIFIED
Richmond, TUNSPECIFIEDUNSPECIFIED
Burgess, DUNSPECIFIEDUNSPECIFIED
Spector, TDUNSPECIFIEDUNSPECIFIED
Tchernof, AUNSPECIFIEDUNSPECIFIED
Marceau, SUNSPECIFIEDUNSPECIFIED
Lathrop, MUNSPECIFIEDUNSPECIFIED
Vohl, MCUNSPECIFIEDUNSPECIFIED
Pastinen, TUNSPECIFIEDUNSPECIFIED
Grundberg, EUNSPECIFIEDUNSPECIFIED
Ahmadi, KRk.ahmadi@surrey.ac.ukUNSPECIFIED
Ainali, CUNSPECIFIEDUNSPECIFIED
Barrett, AUNSPECIFIEDUNSPECIFIED
Bataille, VUNSPECIFIEDUNSPECIFIED
Bell, JTUNSPECIFIEDUNSPECIFIED
Buil, AUNSPECIFIEDUNSPECIFIED
Dermitzakis, ETUNSPECIFIEDUNSPECIFIED
Dimas, ASUNSPECIFIEDUNSPECIFIED
Durbin, RUNSPECIFIEDUNSPECIFIED
Glass, DUNSPECIFIEDUNSPECIFIED
Hassanali, NUNSPECIFIEDUNSPECIFIED
Ingle, CUNSPECIFIEDUNSPECIFIED
Knowles, DUNSPECIFIEDUNSPECIFIED
Krestyaninova, MUNSPECIFIEDUNSPECIFIED
Lindgren, CMUNSPECIFIEDUNSPECIFIED
Lowe, CEUNSPECIFIEDUNSPECIFIED
Meduri, EUNSPECIFIEDUNSPECIFIED
Di Meglio, PUNSPECIFIEDUNSPECIFIED
Min, JLUNSPECIFIEDUNSPECIFIED
Montgomery, SBUNSPECIFIEDUNSPECIFIED
Nestle, FOUNSPECIFIEDUNSPECIFIED
Nica, ACUNSPECIFIEDUNSPECIFIED
Nisbet, JUNSPECIFIEDUNSPECIFIED
O'Rahilly, SUNSPECIFIEDUNSPECIFIED
Parts, LUNSPECIFIEDUNSPECIFIED
Potter, SUNSPECIFIEDUNSPECIFIED
Sandling, JUNSPECIFIEDUNSPECIFIED
Sekowska, MUNSPECIFIEDUNSPECIFIED
Shin, SYUNSPECIFIEDUNSPECIFIED
Small, KSUNSPECIFIEDUNSPECIFIED
Soranzo, NUNSPECIFIEDUNSPECIFIED
Surdulescu, GUNSPECIFIEDUNSPECIFIED
Travers, MEUNSPECIFIEDUNSPECIFIED
Tsaprouni, LUNSPECIFIEDUNSPECIFIED
Tsoka, SUNSPECIFIEDUNSPECIFIED
Wilk, AUNSPECIFIEDUNSPECIFIED
Yang, TPUNSPECIFIEDUNSPECIFIED
Zondervan, KTUNSPECIFIEDUNSPECIFIED
Date : 29 May 2015
Identification Number : 10.1038/ncomms8211
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:32
Last Modified : 17 May 2017 14:50
URI: http://epubs.surrey.ac.uk/id/eprint/828238

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800