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

Research output: Contribution to journalArticle

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Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants. / Allum, Fiona; Shao, Xiaojian; Guénard, Frédéric; Simon, Marie Michelle; Busche, Stephan; Caron, Maxime; Lambourne, John; Lessard, Julie; Tandre, Karolina; Hedman, Åsa K.; Kwan, Tony; Ge, Bing; Rönnblom, Lars; McCarthy, Mark I.; Deloukas, Panos; Richmond, Todd; Burgess, Daniel; Spector, Timothy D.; Tchernof, André; Marceau, Simon; Lathrop, Mark; Vohl, Marie Claude; Pastinen, Tomi; Grundberg, Elin; Ahmadi, Kourosh R.; Ainali, Chrysanthi; Barrett, Amy; Bataille, Veronique; Bell, Jordana T.; Buil, Alfonso; Dermitzakis, Emmanouil T.; Dimas, Antigone S.; Durbin, Richard; Glass, Daniel; Hassanali, Neelam; Ingle, Catherine; Knowles, David; Krestyaninova, Maria; Lindgren, Cecilia M.; Lowe, Christopher E.; Meduri, Eshwar; Di Meglio, Paola; Min, Josine L.; Montgomery, Stephen B.; Nestle, Frank O.; Nica, Alexandra C.; Nisbet, James; O'Rahilly, Stephen; Parts, Leopold; Potter, Simon; Sandling, Johanna; Sekowska, Magdalena; Shin, So Youn; Small, Kerrin S.; Soranzo, Nicole; Surdulescu, Gabriela; Travers, Mary E.; Tsaprouni, Loukia; Tsoka, Sophia; Wilk, Alicja; Yang, Tsun Po; Zondervan, Krina T.

In: Nature Communications, Vol. 6, 7211, 29.05.2015.

Research output: Contribution to journalArticle

Harvard

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 & Zondervan, KT 2015, 'Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants', Nature Communications, vol. 6, 7211. https://doi.org/10.1038/ncomms8211

APA

Allum, F., Shao, X., Guénard, F., Simon, M. M., Busche, S., Caron, M., ... Zondervan, K. T. (2015). Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants. Nature Communications, 6, [7211]. https://doi.org/10.1038/ncomms8211

Vancouver

Allum F, Shao X, Guénard F, Simon MM, Busche S, Caron M et al. Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants. Nature Communications. 2015 May 29;6. 7211. https://doi.org/10.1038/ncomms8211

Author

Allum, Fiona ; Shao, Xiaojian ; Guénard, Frédéric ; Simon, Marie Michelle ; Busche, Stephan ; Caron, Maxime ; Lambourne, John ; Lessard, Julie ; Tandre, Karolina ; Hedman, Åsa K. ; Kwan, Tony ; Ge, Bing ; Rönnblom, Lars ; McCarthy, Mark I. ; Deloukas, Panos ; Richmond, Todd ; Burgess, Daniel ; Spector, Timothy D. ; Tchernof, André ; Marceau, Simon ; Lathrop, Mark ; Vohl, Marie Claude ; Pastinen, Tomi ; Grundberg, Elin ; Ahmadi, Kourosh R. ; Ainali, Chrysanthi ; Barrett, Amy ; Bataille, Veronique ; Bell, Jordana T. ; Buil, Alfonso ; Dermitzakis, Emmanouil T. ; Dimas, Antigone S. ; Durbin, Richard ; Glass, Daniel ; Hassanali, Neelam ; Ingle, Catherine ; Knowles, David ; Krestyaninova, Maria ; Lindgren, Cecilia M. ; Lowe, Christopher E. ; Meduri, Eshwar ; Di Meglio, Paola ; Min, Josine L. ; Montgomery, Stephen B. ; Nestle, Frank O. ; Nica, Alexandra C. ; Nisbet, James ; O'Rahilly, Stephen ; Parts, Leopold ; Potter, Simon ; Sandling, Johanna ; Sekowska, Magdalena ; Shin, So Youn ; Small, Kerrin S. ; Soranzo, Nicole ; Surdulescu, Gabriela ; Travers, Mary E. ; Tsaprouni, Loukia ; Tsoka, Sophia ; Wilk, Alicja ; Yang, Tsun Po ; Zondervan, Krina T. / Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants. In: Nature Communications. 2015 ; Vol. 6.

Bibtex Download

@article{2257da3278374dec97eb1af3a9142560,
title = "Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants",
abstract = "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.",
author = "Fiona Allum and Xiaojian Shao and Fr{\'e}d{\'e}ric Gu{\'e}nard and Simon, {Marie Michelle} and Stephan Busche and Maxime Caron and John Lambourne and Julie Lessard and Karolina Tandre and Hedman, {{\AA}sa K.} and Tony Kwan and Bing Ge and Lars R{\"o}nnblom and McCarthy, {Mark I.} and Panos Deloukas and Todd Richmond and Daniel Burgess and Spector, {Timothy D.} and Andr{\'e} Tchernof and Simon Marceau and Mark Lathrop and Vohl, {Marie Claude} and Tomi Pastinen and Elin Grundberg and Ahmadi, {Kourosh R.} and Chrysanthi Ainali and Amy Barrett and Veronique Bataille and Bell, {Jordana T.} and Alfonso Buil and Dermitzakis, {Emmanouil T.} and Dimas, {Antigone S.} and Richard Durbin and Daniel Glass and Neelam Hassanali and Catherine Ingle and David Knowles and Maria Krestyaninova and Lindgren, {Cecilia M.} and Lowe, {Christopher E.} and Eshwar Meduri and {Di Meglio}, Paola and Min, {Josine L.} and Montgomery, {Stephen B.} and Nestle, {Frank O.} and Nica, {Alexandra C.} and James Nisbet and Stephen O'Rahilly and Leopold Parts and Simon Potter and Johanna Sandling and Magdalena Sekowska and Shin, {So Youn} and Small, {Kerrin S.} and Nicole Soranzo and Gabriela Surdulescu and Travers, {Mary E.} and Loukia Tsaprouni and Sophia Tsoka and Alicja Wilk and Yang, {Tsun Po} and Zondervan, {Krina T.}",
year = "2015",
month = "5",
day = "29",
doi = "10.1038/ncomms8211",
language = "English",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants

AU - Allum, Fiona

AU - Shao, Xiaojian

AU - Guénard, Frédéric

AU - Simon, Marie Michelle

AU - Busche, Stephan

AU - Caron, Maxime

AU - Lambourne, John

AU - Lessard, Julie

AU - Tandre, Karolina

AU - Hedman, Åsa K.

AU - Kwan, Tony

AU - Ge, Bing

AU - Rönnblom, Lars

AU - McCarthy, Mark I.

AU - Deloukas, Panos

AU - Richmond, Todd

AU - Burgess, Daniel

AU - Spector, Timothy D.

AU - Tchernof, André

AU - Marceau, Simon

AU - Lathrop, Mark

AU - Vohl, Marie Claude

AU - Pastinen, Tomi

AU - Grundberg, Elin

AU - Ahmadi, Kourosh R.

AU - Ainali, Chrysanthi

AU - Barrett, Amy

AU - Bataille, Veronique

AU - Bell, Jordana T.

AU - Buil, Alfonso

AU - Dermitzakis, Emmanouil T.

AU - Dimas, Antigone S.

AU - Durbin, Richard

AU - Glass, Daniel

AU - Hassanali, Neelam

AU - Ingle, Catherine

AU - Knowles, David

AU - Krestyaninova, Maria

AU - Lindgren, Cecilia M.

AU - Lowe, Christopher E.

AU - Meduri, Eshwar

AU - Di Meglio, Paola

AU - Min, Josine L.

AU - Montgomery, Stephen B.

AU - Nestle, Frank O.

AU - Nica, Alexandra C.

AU - Nisbet, James

AU - O'Rahilly, Stephen

AU - Parts, Leopold

AU - Potter, Simon

AU - Sandling, Johanna

AU - Sekowska, Magdalena

AU - Shin, So Youn

AU - Small, Kerrin S.

AU - Soranzo, Nicole

AU - Surdulescu, Gabriela

AU - Travers, Mary E.

AU - Tsaprouni, Loukia

AU - Tsoka, Sophia

AU - Wilk, Alicja

AU - Yang, Tsun Po

AU - Zondervan, Krina T.

PY - 2015/5/29

Y1 - 2015/5/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84931274676&partnerID=8YFLogxK

U2 - 10.1038/ncomms8211

DO - 10.1038/ncomms8211

M3 - Article

AN - SCOPUS:84931274676

VL - 6

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 7211

ER -

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