Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke.
Aged
Blood Pressure
Body Mass Index
Brain Ischemia
/ epidemiology
Comorbidity
Datasets as Topic
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genomics
/ methods
Humans
Male
Medical History Taking
Middle Aged
Polymorphism, Single Nucleotide
Predictive Value of Tests
Risk Assessment
/ methods
Smoking
/ epidemiology
United Kingdom
/ epidemiology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 12 2019
20 12 2019
Historique:
received:
10
07
2019
accepted:
28
11
2019
entrez:
22
12
2019
pubmed:
22
12
2019
medline:
9
4
2020
Statut:
epublish
Résumé
Recent genome-wide association studies in stroke have enabled the generation of genomic risk scores (GRS) but their predictive power has been modest compared to established stroke risk factors. Here, using a meta-scoring approach, we develop a metaGRS for ischaemic stroke (IS) and analyse this score in the UK Biobank (n = 395,393; 3075 IS events by age 75). The metaGRS hazard ratio for IS (1.26, 95% CI 1.22-1.31 per metaGRS standard deviation) doubles that of a previous GRS, identifying a subset of individuals at monogenic levels of risk: the top 0.25% of metaGRS have three-fold risk of IS. The metaGRS is similarly or more predictive compared to several risk factors, such as family history, blood pressure, body mass index, and smoking. We estimate the reductions needed in modifiable risk factors for individuals with different levels of genomic risk and suggest that, for individuals with high metaGRS, achieving risk factor levels recommended by current guidelines may be insufficient to mitigate risk.
Identifiants
pubmed: 31862893
doi: 10.1038/s41467-019-13848-1
pii: 10.1038/s41467-019-13848-1
pmc: PMC6925280
doi:
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5819Subventions
Organisme : Medical Research Council
ID : MC_PC_12028
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L003120/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/18/13/33946
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Références
Nat Genet. 2014 Nov;46(11):1173-86
pubmed: 25282103
J Stat Softw. 2010;33(1):1-22
pubmed: 20808728
Lancet. 2016 Oct 8;388(10053):1603-1658
pubmed: 27733283
Hypertension. 2017 Jul 24;:
pubmed: 28739976
Nat Genet. 2013 Apr;45(4):349-51
pubmed: 23535723
Stroke. 2014 Feb;45(2):394-402
pubmed: 24436234
Nat Genet. 2015 Oct;47(10):1121-1130
pubmed: 26343387
Nat Genet. 2017 Jan;49(1):54-64
pubmed: 27841878
Nat Genet. 2018 Sep;50(9):1219-1224
pubmed: 30104762
Bioinformatics. 2010 Nov 15;26(22):2867-73
pubmed: 20926424
Stroke. 2014 Feb;45(2):403-12
pubmed: 24436238
Nat Genet. 2013 Jan;45(1):25-33
pubmed: 23202125
Am J Hum Genet. 2011 Mar 11;88(3):294-305
pubmed: 21376301
Diabetes. 2017 Nov;66(11):2888-2902
pubmed: 28566273
Nat Commun. 2018 Mar 7;9(1):989
pubmed: 29515099
Nat Genet. 2016 Oct;48(10):1151-1161
pubmed: 27618447
Lancet. 2015 Aug 8;386(9993):533-40
pubmed: 26049253
Nat Genet. 2019 Jan;51(1):51-62
pubmed: 30578418
Neurol Genet. 2018 Dec 03;4(6):e293
pubmed: 30584597
N Engl J Med. 2016 Dec 15;375(24):2349-2358
pubmed: 27959714
Nat Genet. 2015 Mar;47(3):291-5
pubmed: 25642630
Nat Genet. 2015 Nov;47(11):1236-41
pubmed: 26414676
Gigascience. 2015 Feb 25;4:7
pubmed: 25722852
Nat Commun. 2019 Jan 18;10(1):333
pubmed: 30659178
Nat Genet. 2017 Mar;49(3):403-415
pubmed: 28135244
Stroke. 2014 Dec;45(12):3754-832
pubmed: 25355838
Nat Genet. 2013 Nov;45(11):1274-1283
pubmed: 24097068
Stroke. 2014 Oct;45(10):2856-2862
pubmed: 25123217
BMJ. 2018 Oct 24;363:k4168
pubmed: 30355576
Nat Genet. 2018 Sep;50(9):1234-1239
pubmed: 30061737
Am J Hum Genet. 2017 Apr 6;100(4):635-649
pubmed: 28366442
Nat Genet. 2010 May;42(5):441-7
pubmed: 20418890
Nat Genet. 2013 Apr;45(4):400-5, 405e1-3
pubmed: 23455638
PLoS Genet. 2010 Feb 26;6(2):e1000864
pubmed: 20195508
Ann Neurol. 2018 Dec;84(6):934-939
pubmed: 30383316
Circ Genom Precis Med. 2019 Jun;12(6):e002481
pubmed: 31184202
Nat Genet. 2017 Jun;49(6):946-952
pubmed: 28416818
J Neurol Neurosurg Psychiatry. 2005 May;76(5):739-41
pubmed: 15834040
Nature. 2018 Oct;562(7726):203-209
pubmed: 30305743
J Am Coll Cardiol. 2018 Oct 16;72(16):1883-1893
pubmed: 30309464
J Am Coll Cardiol. 2018 May 15;71(19):e127-e248
pubmed: 29146535
Nat Genet. 2018 Oct;50(10):1412-1425
pubmed: 30224653
Lancet Neurol. 2019 Jun;18(6):587-599
pubmed: 30975520
PLoS Med. 2015 Mar 31;12(3):e1001779
pubmed: 25826379
Lancet. 2016 Oct 8;388(10053):1459-1544
pubmed: 27733281
Lancet Neurol. 2019 May;18(5):439-458
pubmed: 30871944
Circulation. 2019 Mar 26;139(13):1593-1602
pubmed: 30586733
Stat Med. 2005 Oct 15;24(19):2911-35
pubmed: 16152135
Lancet Neurol. 2012 Nov;11(11):951-62
pubmed: 23041239
Circulation. 2018 Mar 6;137(10):1027-1038
pubmed: 29129827
Eur Heart J. 2016 Nov 14;37(43):3267-3278
pubmed: 27655226
Nat Genet. 2018 Apr;50(4):524-537
pubmed: 29531354
Nature. 2015 Feb 12;518(7538):197-206
pubmed: 25673413