Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
27
09
2019
revised:
01
04
2020
accepted:
03
04
2020
pubmed:
12
4
2020
medline:
21
10
2020
entrez:
12
4
2020
Statut:
ppublish
Résumé
Observational studies point to an inverse correlation between low-density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH. We constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high-density lipoprotein [HDL], and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses. We identified 410, 339, 393, and 317 lipid-related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10 Genetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56-66.
Identifiants
pubmed: 32277781
doi: 10.1002/ana.25740
pmc: PMC7523882
mid: NIHMS1608154
doi:
Substances chimiques
Cholesterol, HDL
0
Cholesterol, LDL
0
Triglycerides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
56-66Subventions
Organisme : NINDS NIH HHS
ID : K23 NS086873
Pays : United States
Organisme : Wellcome Trust
ID : 212946/Z/18/Z
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : K76 AG059992
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG021342
Pays : United States
Organisme : Medical Research Council
ID : MC_U137686851
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_13049
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R01 NS036695
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_14135
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : K07 AG043587
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12026/2
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R01 NS103924
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS069763
Pays : United States
Organisme : NINDS NIH HHS
ID : R03 NS112859
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00017/1
Pays : United Kingdom
Informations de copyright
© 2020 American Neurological Association.
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