Identifying individuals with high risk of Alzheimer's disease using polygenic risk scores.
Alleles
Alzheimer Disease
/ diagnosis
Apolipoproteins E
/ genetics
Case-Control Studies
Gene Frequency
Genetics, Population
/ methods
Genome-Wide Association Study
/ methods
Genotype
Humans
Multifactorial Inheritance
/ genetics
Polymorphism, Single Nucleotide
Reproducibility of Results
Risk Assessment
/ methods
Risk Factors
Sensitivity and Specificity
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 07 2021
23 07 2021
Historique:
received:
28
12
2020
accepted:
02
06
2021
entrez:
24
7
2021
pubmed:
25
7
2021
medline:
11
8
2021
Statut:
epublish
Résumé
Polygenic Risk Scores (PRS) for AD offer unique possibilities for reliable identification of individuals at high and low risk of AD. However, there is little agreement in the field as to what approach should be used for genetic risk score calculations, how to model the effect of APOE, what the optimal p-value threshold (pT) for SNP selection is and how to compare scores between studies and methods. We show that the best prediction accuracy is achieved with a model with two predictors (APOE and PRS excluding APOE region) with pT<0.1 for SNP selection. Prediction accuracy in a sample across different PRS approaches is similar, but individuals' scores and their associated ranking differ. We show that standardising PRS against the population mean, as opposed to the sample mean, makes the individuals' scores comparable between studies. Our work highlights the best strategies for polygenic profiling when assessing individuals for AD risk.
Identifiants
pubmed: 34301930
doi: 10.1038/s41467-021-24082-z
pii: 10.1038/s41467-021-24082-z
pmc: PMC8302739
doi:
Substances chimiques
Apolipoproteins E
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
4506Subventions
Organisme : Medical Research Council
ID : G0902227
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0801418
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG017917
Pays : United States
Organisme : Medical Research Council
ID : MR/K013041/1
Pays : United Kingdom
Organisme : CIHR
Pays : Canada
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : Medical Research Council
ID : G0600237
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0300429
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17112
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U01 AG046152
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG061356
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG032984
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG030146
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : Medical Research Council
ID : MR/M009076/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L023784/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : UKDRI-3003
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T04604X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L501517/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG036836
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Informations de copyright
© 2021. The Author(s).
Références
Nat Neurosci. 2020 Aug;23(8):927-938
pubmed: 32514138
Alzheimers Dement. 2013 Jan;9(1):63-75.e2
pubmed: 23305823
Biomed Res Int. 2016;2016:3912175
pubmed: 27868062
PLoS Genet. 2012;8(6):e1002707
pubmed: 22685416
Brain Commun. 2020;2(1):fcz047
pubmed: 32226939
Nat Genet. 2019 Mar;51(3):414-430
pubmed: 30820047
Cardiovasc Diabetol. 2016 Jan 22;15:12
pubmed: 26800892
PLoS Genet. 2010 Dec 02;6(12):e1001230
pubmed: 21151957
Neurol Genet. 2020 Sep 08;6(5):e506
pubmed: 33134508
Nat Genet. 2013 Dec;45(12):1452-8
pubmed: 24162737
Cell. 2017 Jun 15;169(7):1276-1290.e17
pubmed: 28602351
J Alzheimers Dis. 2020;74(4):1271-1283
pubmed: 32250305
Hum Hered. 2021 Feb 12;:1-11
pubmed: 33582669
Neuropathol Appl Neurobiol. 1984 May-Jun;10(3):185-207
pubmed: 6234474
Curr Alzheimer Res. 2012 Jul;9(6):628-45
pubmed: 22471860
Cell Rep. 2019 Feb 19;26(8):2078-2087.e3
pubmed: 30784590
Bioinformatics. 2015 May 1;31(9):1466-8
pubmed: 25550326
Cell Rep. 2019 Apr 23;27(4):1293-1306.e6
pubmed: 31018141
Ann Neurol. 2019 Sep;86(3):427-435
pubmed: 31199530
Gigascience. 2015 Feb 25;4:7
pubmed: 25722852
Neurology. 2010 Jan 19;74(3):201-9
pubmed: 20042704
Immunity. 2017 Sep 19;47(3):566-581.e9
pubmed: 28930663
Curr Alzheimer Res. 2012 Jul;9(6):646-63
pubmed: 22471867
Science. 1993 Aug 13;261(5123):921-3
pubmed: 8346443
Nature. 2014 Jul 24;511(7510):421-7
pubmed: 25056061
Science. 2020 Oct 2;370(6512):61-66
pubmed: 33004512
Nat Rev Neurol. 2013 Feb;9(2):106-18
pubmed: 23296339
Nat Genet. 2019 Feb;51(2):277-284
pubmed: 30510236
Neurology. 2016 Mar 22;86(12):1128-35
pubmed: 26911640
Nat Commun. 2020 Sep 23;11(1):4799
pubmed: 32968074
Nat Neurosci. 2020 Mar;23(3):311-322
pubmed: 32112059
Nat Commun. 2019 Nov 8;10(1):5086
pubmed: 31704910
Neurobiol Aging. 2021 Mar;99:101.e1-101.e9
pubmed: 33164815
J Alzheimers Dis. 2018;64(s1):S161-S189
pubmed: 29865057
EBioMedicine. 2020 Sep;59:102954
pubmed: 32818802
Am J Epidemiol. 2017 Nov 1;186(9):1026-1034
pubmed: 28641372
Neuron. 2019 Sep 4;103(5):820-835.e7
pubmed: 31301936
JAMA. 2002 Feb 13;287(6):742-8
pubmed: 11851541
N Engl J Med. 2016 Jul 7;375(1):93-4
pubmed: 27406362
Nat Commun. 2019 Apr 16;10(1):1776
pubmed: 30992449
Nature. 2009 Aug 6;460(7256):748-52
pubmed: 19571811
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
Am J Hum Genet. 2015 Oct 1;97(4):576-92
pubmed: 26430803
Neurology. 2010 Nov 9;75(19):1726-9
pubmed: 21060095
PLoS Med. 2015 Mar 31;12(3):e1001779
pubmed: 25826379
Lancet. 1997 Jan 18;349(9046):151-4
pubmed: 9111537
Alzheimers Dement. 2019 Oct;15(10):1333-1347
pubmed: 31473137
Brain. 2015 Dec;138(Pt 12):3673-84
pubmed: 26490334
Am J Epidemiol. 2011 Jun 15;173(12):1357-64
pubmed: 21498624
JAMA. 1994 Dec 7;272(21):1666-71
pubmed: 7966894
Neurology. 1993 Nov;43(11):2412-4
pubmed: 8232972
Eur J Hum Genet. 2019 Feb;27(2):244-253
pubmed: 30258121
Neurobiol Aging. 2020 Sep;93:69-77
pubmed: 32464432
Alzheimers Dement (Amst). 2021 Jan 22;13(1):e12142
pubmed: 33532541
Elife. 2020 Oct 19;9:
pubmed: 33074098
Alzheimers Dement. 2011 May;7(3):280-92
pubmed: 21514248