Machine learning suggests polygenic risk for cognitive dysfunction in amyotrophic lateral sclerosis.
amyotrophic lateral sclerosis
cognition
frontotemporal dementia
machine learning
polygenic score
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
11 01 2021
11 01 2021
Historique:
received:
24
04
2020
revised:
27
10
2020
accepted:
30
10
2020
pubmed:
4
12
2020
medline:
6
10
2022
entrez:
3
12
2020
Statut:
ppublish
Résumé
Amyotrophic lateral sclerosis (ALS) is a multi-system disease characterized primarily by progressive muscle weakness. Cognitive dysfunction is commonly observed in patients; however, factors influencing risk for cognitive dysfunction remain elusive. Using sparse canonical correlation analysis (sCCA), an unsupervised machine-learning technique, we observed that single nucleotide polymorphisms collectively associate with baseline cognitive performance in a large ALS patient cohort (N = 327) from the multicenter Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium. We demonstrate that a polygenic risk score derived using sCCA relates to longitudinal cognitive decline in the same cohort and also to in vivo cortical thinning in the orbital frontal cortex, anterior cingulate cortex, lateral temporal cortex, premotor cortex, and hippocampus (N = 90) as well as post-mortem motor cortical neuronal loss (N = 87) in independent ALS cohorts from the University of Pennsylvania Integrated Neurodegenerative Disease Biobank. Our findings suggest that common genetic polymorphisms may exert a polygenic contribution to the risk of cortical disease vulnerability and cognitive dysfunction in ALS.
Identifiants
pubmed: 33270986
doi: 10.15252/emmm.202012595
pmc: PMC7799365
doi:
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12595Subventions
Organisme : NIA NIH HHS
ID : R01 AG054060
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG017586
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS092091
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG066597
Pays : United States
Organisme : NINDS NIH HHS
ID : F31 NS106754
Pays : United States
Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
Références
Alzheimers Dement. 2014 Jul;10(4):477-484.e1
pubmed: 23978324
J Neurol Sci. 1999 Oct 31;169(1-2):13-21
pubmed: 10540002
Ann Neurol. 2016 Feb;79(2):272-87
pubmed: 26583316
Lancet Neurol. 2012 Mar;11(3):232-40
pubmed: 22305801
Stat Appl Genet Mol Biol. 2009;8:Article28
pubmed: 19572827
IEEE Trans Med Imaging. 2010 Jun;29(6):1310-20
pubmed: 20378467
Cortex. 2018 Apr;101:163-171
pubmed: 29477906
JAMA Neurol. 2013 Nov;70(11):1411-7
pubmed: 24081456
Nat Commun. 2019 Jul 25;10(1):3328
pubmed: 31346163
Amyotroph Lateral Scler Frontotemporal Degener. 2014 Mar;15(1-2):9-14
pubmed: 23781974
J Neurol Neurosurg Psychiatry. 2016 Jun;87(6):611-9
pubmed: 26283685
Neuron. 2011 Oct 20;72(2):257-68
pubmed: 21944779
PLoS One. 2013;8(2):e57584
pubmed: 23460879
Nat Genet. 2016 Oct;48(10):1279-83
pubmed: 27548312
Brain. 2018 Jan 1;141(1):288-301
pubmed: 29228211
Neuroimage. 2009 Jan 1;44(1):83-98
pubmed: 18501637
Acta Neuropathol. 2015 Sep;130(3):363-72
pubmed: 26022924
Amyotroph Lateral Scler Frontotemporal Degener. 2017 May;18(3-4):153-174
pubmed: 28054827
Neurology. 2014 Aug 5;83(6):502-9
pubmed: 24994843
Science. 2009 Feb 27;323(5918):1208-1211
pubmed: 19251628
Bioinformatics. 2010 Mar 1;26(5):589-95
pubmed: 20080505
Neurobiol Aging. 2014 Jun;35(6):1473-82
pubmed: 24373676
Hum Brain Mapp. 2016 Apr;37(4):1614-26
pubmed: 26833930
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
Nat Genet. 2016 Oct;48(10):1284-1287
pubmed: 27571263
Neuroimage. 2014 May 15;92:381-97
pubmed: 24530839
Neurology. 2018 Oct 9;91(15):e1370-e1380
pubmed: 30209236
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
Neurology. 2016 Sep 6;87(10):1019-23
pubmed: 27488596
J Neurol Neurosurg Psychiatry. 2019 Feb;90(2):141-147
pubmed: 30076267
Neurology. 2016 Sep 6;87(10):1024-30
pubmed: 27488601
Genet Med. 2019 Aug;21(8):1705-1707
pubmed: 30635622
Neuroimage. 2014 Oct 1;99:166-79
pubmed: 24879923
EMBO Mol Med. 2021 Jan 11;13(1):e12595
pubmed: 33270986
Nature. 1993 Mar 4;362(6415):59-62
pubmed: 8446170
Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9
pubmed: 11464847
Ann Neurol. 2014 Jul;76(1):120-33
pubmed: 24931836
J Neurol Neurosurg Psychiatry. 2017 Feb;88(2):152-164
pubmed: 27899424
Amyotroph Lateral Scler Frontotemporal Degener. 2019 Feb;20(1-2):1-11
pubmed: 30585510
Neuron. 2011 Oct 20;72(2):245-56
pubmed: 21944778
J Neurol Neurosurg Psychiatry. 2017 Dec;88(12):1042-1044
pubmed: 28642287
Bioinformatics. 2015 Jul 1;31(13):2202-4
pubmed: 25701572
Nat Genet. 2016 Sep;48(9):1043-8
pubmed: 27455348
Nat Neurosci. 2015 May;18(5):631-6
pubmed: 25803835
Ann Neurol. 2019 Apr;85(4):470-481
pubmed: 30723964
Neurobiol Aging. 2019 Jan;73:190-199
pubmed: 30368160
JAMA. 2019 May 14;321(18):1820-1821
pubmed: 30958510
Neuron. 2018 Mar 21;97(6):1268-1283.e6
pubmed: 29566793
JAMA Neurol. 2018 Jul 1;75(7):860-875
pubmed: 29630712
Neurology. 2013 Apr 23;80(17):1590-7
pubmed: 23553481
Database (Oxford). 2018 Jan 1;2018:
pubmed: 30576484
Am J Hum Genet. 2007 Sep;81(3):559-75
pubmed: 17701901
Acta Neuropathol. 2011 Jul;122(1):111-3
pubmed: 21644037
Nat Genet. 2006 Aug;38(8):904-9
pubmed: 16862161
Nat Genet. 2016 Sep;48(9):1037-42
pubmed: 27455347
Hum Mol Genet. 2003 Dec 1;12(23):3195-205
pubmed: 14559776
Lancet Neurol. 2008 May;7(5):409-16
pubmed: 18396105
Acta Neuropathol. 2011 Mar;121(3):373-80
pubmed: 21104415
Mol Psychiatry. 2015 Dec;20(12):1588-95
pubmed: 25687773
Amyotroph Lateral Scler. 2011 Jan;12(1):45-51
pubmed: 20849323
Acta Neuropathol. 2017 May;133(5):825-837
pubmed: 28271184
BMC Proc. 2007;1 Suppl 1:S119
pubmed: 18466460
J Histochem Cytochem. 2016 Jan;64(1):54-66
pubmed: 26538548
Neurology. 2009 Nov 17;73(20):1686-92
pubmed: 19917992
Nat Commun. 2018 Aug 1;9(1):3003
pubmed: 30068943
Science. 2006 Oct 6;314(5796):130-3
pubmed: 17023659
Ann Neurol. 2019 May;85(5):630-643
pubmed: 30851133
Neuroimage. 2014 Jan 1;84:698-711
pubmed: 24096125
Biostatistics. 2009 Jul;10(3):515-34
pubmed: 19377034
Neuroimage. 2010 Apr 15;50(3):1004-16
pubmed: 20083207
Bioinformatics. 2017 Jul 15;33(14):i341-i349
pubmed: 28881979
Nat Genet. 2009 Oct;41(10):1083-7
pubmed: 19734901
Acta Neuropathol. 2009 Feb;117(2):137-49
pubmed: 19125255
Arch Neurol. 2009 Dec;66(12):1483-8
pubmed: 20008652
J Neurol Neurosurg Psychiatry. 2015 Feb;86(2):168-73
pubmed: 24769471