Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis

Marta F. Nabais; Tian Lin; Beben Benyamin; Kelly L. Williams; Fleur C. Garton; Anna A.E. Vinkhuyzen; Futao Zhang; Costanza L. Vallerga; Restuadi Restuadi; Anna Freydenzon; Ramona A.J. Zwamborn; Paul J. Hop; Matthew R. Robinson; Jacob Gratten; Peter M. Visscher; Eilis Hannon; Jonathan Mill; Matthew A. Brown; Nigel G. Laing; Karen A. Mather; Perminder S. Sachdev; Shyuan T. Ngo; Frederik J. Steyn; Leanne Wallace; Anjali K. Henders; Merrilee Needham; Jan H. Veldink; Susan Mathers; Garth Nicholson; Dominic B. Rowe; Robert D. Henderson; Pamela A. McCombe; Roger Pamphlett; Jian Yang; Ian P. Blair; Allan F. McRae; Naomi R. Wray

doi:10.1038/s41525-020-0118-3

Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis

Marta F. Nabais, Tian Lin, Beben Benyamin, Kelly L. Williams, Fleur C. Garton, Anna A.E. Vinkhuyzen, Futao Zhang, Costanza L. Vallerga, Restuadi Restuadi, Anna Freydenzon, Ramona A.J. Zwamborn, Paul J. Hop, Matthew R. Robinson, Jacob Gratten, Peter M. Visscher, Eilis Hannon, Jonathan Mill, Matthew A. Brown, Nigel G. Laing, Karen A. MatherPerminder S. Sachdev, Shyuan T. Ngo, Frederik J. Steyn, Leanne Wallace, Anjali K. Henders, Merrilee Needham, Jan H. Veldink, Susan Mathers, Garth Nicholson, Dominic B. Rowe, Robert D. Henderson, Pamela A. McCombe, Roger Pamphlett, Jian Yang, Ian P. Blair, Allan F. McRae, Naomi R. Wray

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI_95% = [0.62–0.68], p = 8.3 × 10⁻²²). The maximum AUC achieved was 0.69 (CI_95% = [0.66–0.71], p = 4.3 × 10⁻³⁴) when cell-type proportion was included in the predictor.

Original language	English
Article number	10
Journal	npj Genomic Medicine
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s41525-020-0118-3
Publication status	Published or Issued - 1 Dec 2020
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

Access to Document

10.1038/s41525-020-0118-3

Cite this

Nabais, M. F., Lin, T., Benyamin, B., Williams, K. L., Garton, F. C., Vinkhuyzen, A. A. E., Zhang, F., Vallerga, C. L., Restuadi, R., Freydenzon, A., Zwamborn, R. A. J., Hop, P. J., Robinson, M. R., Gratten, J., Visscher, P. M., Hannon, E., Mill, J., Brown, M. A., Laing, N. G., ... Wray, N. R. (2020). Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis. npj Genomic Medicine, 5(1), Article 10. https://doi.org/10.1038/s41525-020-0118-3

@article{da0636a0373844eb99f3ae0d393e8677,

title = "Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis",

abstract = "We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI95% = [0.62–0.68], p = 8.3 × 10−22). The maximum AUC achieved was 0.69 (CI95% = [0.66–0.71], p = 4.3 × 10−34) when cell-type proportion was included in the predictor.",

author = "Nabais, {Marta F.} and Tian Lin and Beben Benyamin and Williams, {Kelly L.} and Garton, {Fleur C.} and Vinkhuyzen, {Anna A.E.} and Futao Zhang and Vallerga, {Costanza L.} and Restuadi Restuadi and Anna Freydenzon and Zwamborn, {Ramona A.J.} and Hop, {Paul J.} and Robinson, {Matthew R.} and Jacob Gratten and Visscher, {Peter M.} and Eilis Hannon and Jonathan Mill and Brown, {Matthew A.} and Laing, {Nigel G.} and Mather, {Karen A.} and Sachdev, {Perminder S.} and Ngo, {Shyuan T.} and Steyn, {Frederik J.} and Leanne Wallace and Henders, {Anjali K.} and Merrilee Needham and Veldink, {Jan H.} and Susan Mathers and Garth Nicholson and Rowe, {Dominic B.} and Henderson, {Robert D.} and McCombe, {Pamela A.} and Roger Pamphlett and Jian Yang and Blair, {Ian P.} and McRae, {Allan F.} and Wray, {Naomi R.}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41525-020-0118-3",

language = "English",

volume = "5",

journal = "npj Genomic Medicine",

issn = "2056-7944",

publisher = "Nature Publishing Group",

number = "1",

}

Nabais, MF, Lin, T, Benyamin, B, Williams, KL, Garton, FC, Vinkhuyzen, AAE, Zhang, F, Vallerga, CL, Restuadi, R, Freydenzon, A, Zwamborn, RAJ, Hop, PJ, Robinson, MR, Gratten, J, Visscher, PM, Hannon, E, Mill, J, Brown, MA, Laing, NG, Mather, KA, Sachdev, PS, Ngo, ST, Steyn, FJ, Wallace, L, Henders, AK, Needham, M, Veldink, JH, Mathers, S, Nicholson, G, Rowe, DB, Henderson, RD, McCombe, PA, Pamphlett, R, Yang, J, Blair, IP, McRae, AF & Wray, NR 2020, 'Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis', npj Genomic Medicine, vol. 5, no. 1, 10. https://doi.org/10.1038/s41525-020-0118-3

TY - JOUR

T1 - Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis

AU - Nabais, Marta F.

AU - Lin, Tian

AU - Benyamin, Beben

AU - Williams, Kelly L.

AU - Garton, Fleur C.

AU - Vinkhuyzen, Anna A.E.

AU - Zhang, Futao

AU - Vallerga, Costanza L.

AU - Restuadi, Restuadi

AU - Freydenzon, Anna

AU - Zwamborn, Ramona A.J.

AU - Hop, Paul J.

AU - Robinson, Matthew R.

AU - Gratten, Jacob

AU - Visscher, Peter M.

AU - Hannon, Eilis

AU - Mill, Jonathan

AU - Brown, Matthew A.

AU - Laing, Nigel G.

AU - Mather, Karen A.

AU - Sachdev, Perminder S.

AU - Ngo, Shyuan T.

AU - Steyn, Frederik J.

AU - Wallace, Leanne

AU - Henders, Anjali K.

AU - Needham, Merrilee

AU - Veldink, Jan H.

AU - Mathers, Susan

AU - Nicholson, Garth

AU - Rowe, Dominic B.

AU - Henderson, Robert D.

AU - McCombe, Pamela A.

AU - Pamphlett, Roger

AU - Yang, Jian

AU - Blair, Ian P.

AU - McRae, Allan F.

AU - Wray, Naomi R.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI95% = [0.62–0.68], p = 8.3 × 10−22). The maximum AUC achieved was 0.69 (CI95% = [0.66–0.71], p = 4.3 × 10−34) when cell-type proportion was included in the predictor.

AB - We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI95% = [0.62–0.68], p = 8.3 × 10−22). The maximum AUC achieved was 0.69 (CI95% = [0.66–0.71], p = 4.3 × 10−34) when cell-type proportion was included in the predictor.

UR - http://www.scopus.com/inward/record.url?scp=85080109617&partnerID=8YFLogxK

U2 - 10.1038/s41525-020-0118-3

DO - 10.1038/s41525-020-0118-3

M3 - Article

AN - SCOPUS:85080109617

SN - 2056-7944

VL - 5

JO - npj Genomic Medicine

JF - npj Genomic Medicine

IS - 1

M1 - 10

ER -

Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Cite this