---
_id: '7708'
abstract:
- lang: eng
  text: 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.
article_number: '10'
article_processing_charge: No
article_type: original
author:
- first_name: Marta F.
  full_name: Nabais, Marta F.
  last_name: Nabais
- first_name: Tian
  full_name: Lin, Tian
  last_name: Lin
- first_name: Beben
  full_name: Benyamin, Beben
  last_name: Benyamin
- first_name: Kelly L.
  full_name: Williams, Kelly L.
  last_name: Williams
- first_name: Fleur C.
  full_name: Garton, Fleur C.
  last_name: Garton
- first_name: Anna A. E.
  full_name: Vinkhuyzen, Anna A. E.
  last_name: Vinkhuyzen
- first_name: Futao
  full_name: Zhang, Futao
  last_name: Zhang
- first_name: Costanza L.
  full_name: Vallerga, Costanza L.
  last_name: Vallerga
- first_name: Restuadi
  full_name: Restuadi, Restuadi
  last_name: Restuadi
- first_name: Anna
  full_name: Freydenzon, Anna
  last_name: Freydenzon
- first_name: Ramona A. J.
  full_name: Zwamborn, Ramona A. J.
  last_name: Zwamborn
- first_name: Paul J.
  full_name: Hop, Paul J.
  last_name: Hop
- first_name: Matthew Richard
  full_name: Robinson, Matthew Richard
  id: E5D42276-F5DA-11E9-8E24-6303E6697425
  last_name: Robinson
  orcid: 0000-0001-8982-8813
- first_name: Jacob
  full_name: Gratten, Jacob
  last_name: Gratten
- first_name: Peter M.
  full_name: Visscher, Peter M.
  last_name: Visscher
- first_name: Eilis
  full_name: Hannon, Eilis
  last_name: Hannon
- first_name: Jonathan
  full_name: Mill, Jonathan
  last_name: Mill
- first_name: Matthew A.
  full_name: Brown, Matthew A.
  last_name: Brown
- first_name: Nigel G.
  full_name: Laing, Nigel G.
  last_name: Laing
- first_name: Karen A.
  full_name: Mather, Karen A.
  last_name: Mather
- first_name: Perminder S.
  full_name: Sachdev, Perminder S.
  last_name: Sachdev
- first_name: Shyuan T.
  full_name: Ngo, Shyuan T.
  last_name: Ngo
- first_name: Frederik J.
  full_name: Steyn, Frederik J.
  last_name: Steyn
- first_name: Leanne
  full_name: Wallace, Leanne
  last_name: Wallace
- first_name: Anjali K.
  full_name: Henders, Anjali K.
  last_name: Henders
- first_name: Merrilee
  full_name: Needham, Merrilee
  last_name: Needham
- first_name: Jan H.
  full_name: Veldink, Jan H.
  last_name: Veldink
- first_name: Susan
  full_name: Mathers, Susan
  last_name: Mathers
- first_name: Garth
  full_name: Nicholson, Garth
  last_name: Nicholson
- first_name: Dominic B.
  full_name: Rowe, Dominic B.
  last_name: Rowe
- first_name: Robert D.
  full_name: Henderson, Robert D.
  last_name: Henderson
- first_name: Pamela A.
  full_name: McCombe, Pamela A.
  last_name: McCombe
- first_name: Roger
  full_name: Pamphlett, Roger
  last_name: Pamphlett
- first_name: Jian
  full_name: Yang, Jian
  last_name: Yang
- first_name: Ian P.
  full_name: Blair, Ian P.
  last_name: Blair
- first_name: Allan F.
  full_name: McRae, Allan F.
  last_name: McRae
- first_name: Naomi R.
  full_name: Wray, Naomi R.
  last_name: Wray
citation:
  ama: Nabais MF, Lin T, Benyamin B, et al. Significant out-of-sample classification
    from methylation profile scoring for amyotrophic lateral sclerosis. <i>npj Genomic
    Medicine</i>. 2020;5. doi:<a href="https://doi.org/10.1038/s41525-020-0118-3">10.1038/s41525-020-0118-3</a>
  apa: Nabais, M. F., Lin, T., Benyamin, B., Williams, K. L., Garton, F. C., Vinkhuyzen,
    A. A. E., … Wray, N. R. (2020). Significant out-of-sample classification from
    methylation profile scoring for amyotrophic lateral sclerosis. <i>Npj Genomic
    Medicine</i>. Springer Nature. <a href="https://doi.org/10.1038/s41525-020-0118-3">https://doi.org/10.1038/s41525-020-0118-3</a>
  chicago: Nabais, Marta F., Tian Lin, Beben Benyamin, Kelly L. Williams, Fleur C.
    Garton, Anna A. E. Vinkhuyzen, Futao Zhang, et al. “Significant Out-of-Sample
    Classification from Methylation Profile Scoring for Amyotrophic Lateral Sclerosis.”
    <i>Npj Genomic Medicine</i>. Springer Nature, 2020. <a href="https://doi.org/10.1038/s41525-020-0118-3">https://doi.org/10.1038/s41525-020-0118-3</a>.
  ieee: M. F. Nabais <i>et al.</i>, “Significant out-of-sample classification from
    methylation profile scoring for amyotrophic lateral sclerosis,” <i>npj Genomic
    Medicine</i>, vol. 5. Springer Nature, 2020.
  ista: 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. 5, 10.
  mla: Nabais, Marta F., et al. “Significant Out-of-Sample Classification from Methylation
    Profile Scoring for Amyotrophic Lateral Sclerosis.” <i>Npj Genomic Medicine</i>,
    vol. 5, 10, Springer Nature, 2020, doi:<a href="https://doi.org/10.1038/s41525-020-0118-3">10.1038/s41525-020-0118-3</a>.
  short: M.F. Nabais, T. Lin, B. Benyamin, K.L. Williams, F.C. Garton, A.A.E. Vinkhuyzen,
    F. Zhang, C.L. Vallerga, R. Restuadi, A. Freydenzon, R.A.J. Zwamborn, P.J. Hop,
    M.R. Robinson, J. Gratten, P.M. Visscher, E. Hannon, J. Mill, M.A. Brown, N.G.
    Laing, K.A. Mather, P.S. Sachdev, S.T. Ngo, F.J. Steyn, L. Wallace, A.K. Henders,
    M. Needham, J.H. Veldink, S. Mathers, G. Nicholson, D.B. Rowe, R.D. Henderson,
    P.A. McCombe, R. Pamphlett, J. Yang, I.P. Blair, A.F. McRae, N.R. Wray, Npj Genomic
    Medicine 5 (2020).
date_created: 2020-04-30T10:39:54Z
date_published: 2020-02-27T00:00:00Z
date_updated: 2021-01-12T08:14:59Z
day: '27'
doi: 10.1038/s41525-020-0118-3
extern: '1'
intvolume: '         5'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41525-020-0118-3
month: '02'
oa: 1
oa_version: Published Version
publication: npj Genomic Medicine
publication_identifier:
  issn:
  - 2056-7944
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
status: public
title: Significant out-of-sample classification from methylation profile scoring for
  amyotrophic lateral sclerosis
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 5
year: '2020'
...