A machine learning case-control classifier for schizophrenia based on DNA methylation in blood.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
03 08 2021
03 08 2021
Historique:
received:
31
05
2021
accepted:
22
06
2021
revised:
07
06
2021
entrez:
3
8
2021
pubmed:
4
8
2021
medline:
6
8
2021
Statut:
epublish
Résumé
Epigenetic dysregulation is thought to contribute to the etiology of schizophrenia (SZ), but the cell type-specificity of DNA methylation makes population-based epigenetic studies of SZ challenging. To train an SZ case-control classifier based on DNA methylation in blood, therefore, we focused on human genomic regions of systemic interindividual epigenetic variation (CoRSIVs), a subset of which are represented on the Illumina Human Methylation 450K (HM450) array. HM450 DNA methylation data on whole blood of 414 SZ cases and 433 non-psychiatric controls were used as training data for a classification algorithm with built-in feature selection, sparse partial least squares discriminate analysis (SPLS-DA); application of SPLS-DA to HM450 data has not been previously reported. Using the first two SPLS-DA dimensions we calculated a "risk distance" to identify individuals with the highest probability of SZ. The model was then evaluated on an independent HM450 data set on 353 SZ cases and 322 non-psychiatric controls. Our CoRSIV-based model classified 303 individuals as cases with a positive predictive value (PPV) of 80%, far surpassing the performance of a model based on polygenic risk score (PRS). Importantly, risk distance (based on CoRSIV methylation) was not associated with medication use, arguing against reverse causality. Risk distance and PRS were positively correlated (Pearson r = 0.28, P = 1.28 × 10
Identifiants
pubmed: 34341337
doi: 10.1038/s41398-021-01496-3
pii: 10.1038/s41398-021-01496-3
pmc: PMC8329061
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
412Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK111522
Pays : United States
Organisme : U.S. Department of Agriculture (United States Department of Agriculture)
ID : CRIS 3092-5-001-059
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : 1R01DK111522
Informations de copyright
© 2021. The Author(s).
Références
Genome Biol. 2016 Aug 30;17(1):176
pubmed: 27572077
Transl Psychiatry. 2019 Nov 14;9(1):300
pubmed: 31727878
JAMA Psychiatry. 2016 May 1;73(5):506-14
pubmed: 27074206
Br J Psychiatry. 1994 May;164(5):593-9
pubmed: 7921708
Schizophr Bull. 2020 Feb 26;46(2):319-327
pubmed: 31165892
Genome Biol. 2018 Jan 9;19(1):2
pubmed: 29310692
Biol Psychiatry. 2020 Dec 1;88(11):e53-e55
pubmed: 33153529
Nature. 2009 Aug 6;460(7256):748-52
pubmed: 19571811
Genome Biol. 2015 Jun 11;16:118
pubmed: 26062908
Am J Med Genet B Neuropsychiatr Genet. 2019 Jan;180(1):80-85
pubmed: 30516002
Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jul 13;101:109925
pubmed: 32194204
Nature. 2008 Sep 11;455(7210):237-41
pubmed: 18668038
Schizophr Bull. 2016 Mar;42(2):406-14
pubmed: 26056378
Lancet. 2016 Jul 2;388(10039):86-97
pubmed: 26777917
Nature. 2010 Nov 11;468(7321):187-93
pubmed: 21068826
BMC Bioinformatics. 2012 May 08;13:86
pubmed: 22568884
PLoS One. 2013 May 17;8(5):e63812
pubmed: 23691101
Nat Neurosci. 2014 Sep;17(9):1164-70
pubmed: 25129077
Clin Epigenetics. 2014 Feb 03;6(1):4
pubmed: 24485148
Arch Gen Psychiatry. 1991 Aug;48(8):764-70
pubmed: 1883262
Int J Mol Sci. 2017 Mar 14;18(3):
pubmed: 28335437
Proc Natl Acad Sci U S A. 2010 Jan 26;107 Suppl 1:1757-64
pubmed: 20080672
J R Stat Soc Series B Stat Methodol. 2010 Jan;72(1):3-25
pubmed: 20107611
Biol Psychiatry. 2004 May 15;55(10):965-70
pubmed: 15121478
PLoS One. 2012;7(10):e46705
pubmed: 23071618
Nature. 2014 Jul 24;511(7510):421-7
pubmed: 25056061
Epigenetics. 2014 Oct;9(10):1382-96
pubmed: 25424692
J Clin Psychiatry. 2002 Sep;63(9):812-6
pubmed: 12363123
JAMA Psychiatry. 2014 Mar;71(3):255-64
pubmed: 24402055
Front Public Health. 2017 Nov 20;5:307
pubmed: 29209603
Arch Gen Psychiatry. 2003 Dec;60(12):1187-92
pubmed: 14662550
PLoS Genet. 2010 Dec 23;6(12):e1001252
pubmed: 21203497
JAMA Psychiatry. 2020 Jun 1;77(6):628-636
pubmed: 32049268
JAMA Psychiatry. 2019 Jun 1;76(6):563-564
pubmed: 31017638
Nat Genet. 2013 Jun;45(6):580-5
pubmed: 23715323
PLoS Comput Biol. 2017 Nov 3;13(11):e1005752
pubmed: 29099853
Genome Biol. 2019 Jun 3;20(1):105
pubmed: 31155008
Nat Neurosci. 2016 Jan;19(1):48-54
pubmed: 26619357
Mol Psychiatry. 2010 Jun;15(6):615-28
pubmed: 19048012
Oral Oncol. 2019 Mar;90:94-101
pubmed: 30846184
Nucleic Acids Res. 2019 Jan 8;47(D1):D1005-D1012
pubmed: 30445434
NPJ Schizophr. 2017 Feb 24;3:11
pubmed: 28560257
Int J Epidemiol. 2015 Oct;44(5):1706-21
pubmed: 26286434
Nat Genet. 2018 Mar;50(3):381-389
pubmed: 29483656
Transl Psychiatry. 2017 Aug 1;7(8):e1187
pubmed: 28763057
Stat Appl Genet Mol Biol. 2018 Sep 8;17(5):
pubmed: 30205662
J Psychiatr Res. 2019 Jul;114:41-47
pubmed: 31022588
Annu Rev Public Health. 2020 Apr 2;41:21-36
pubmed: 31577910
Epigenetics. 2015;10(11):1024-32
pubmed: 26457534
Schizophr Res. 2005 Jul 15;76(2-3):135-57
pubmed: 15949648
Stat Appl Genet Mol Biol. 2010;9:Article17
pubmed: 20361856
Am J Public Health. 2010 Dec;100(12):2464-72
pubmed: 20966369
Epigenomics. 2019 Nov 1;11(15):1647-1649
pubmed: 31729252
Annu Rev Nutr. 2007;27:363-88
pubmed: 17465856
Nutrients. 2019 Mar 13;11(3):
pubmed: 30871219
Nat Neurosci. 2016 Jan;19(1):40-7
pubmed: 26619358
Front Genet. 2019 Apr 04;10:268
pubmed: 31019524
JAMA Psychiatry. 2021 Feb 1;78(2):127-128
pubmed: 32804995
Biol Psychiatry. 2021 Feb 1;89(3):215-226
pubmed: 32381277
Mol Autism. 2017 May 22;8:21
pubmed: 28540026