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  • Falcone, Guido J.Yale University (author)

Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • 2020-05-07
  • Wiley,2020
  • 11 s.

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  • LIBRIS-ID:oai:lup.lub.lu.se:2f318fd5-e74e-4926-84f4-bad8c082b46c
  • https://lup.lub.lu.se/record/2f318fd5-e74e-4926-84f4-bad8c082b46cURI
  • https://doi.org/10.1002/ana.25740DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Objective: 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. Methods: 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. Results: 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 × 10-100). While one SD increase in the PRSs for total cholesterol (odds ratio [OR] = 0.92; 95% confidence interval [CI] = 0.85–0.99; p = 0.03) and LDL cholesterol (OR = 0.88; 95% CI = 0.81–0.95; p = 0.002) were inversely associated with ICH risk, no significant associations were found for HDL and triglycerides (both p > 0.05). MR analyses indicated that 1mmol/L (38.67mg/dL) increase of genetically instrumented total and LDL cholesterol were associated with 23% (OR = 0.77; 95% CI = 0.65–0.98; p = 0.03) and 41% lower risks of ICH (OR = 0.59; 95% CI = 0.42–0.82; p = 0.002), respectively. Interpretation: 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.

Subject headings and genre

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  • Kirsch, ElaynaYale University (author)
  • Acosta, Julian N.Yale University (author)
  • Noche, Rommell B.Yale University (author)
  • Leasure, AudreyYale University (author)
  • Marini, SandroMassachusetts General Hospital (author)
  • Chung, JaeyoonMassachusetts General Hospital (author)
  • Selim, MagdyBeth Israel Deaconess Medical Center,Harvard University (author)
  • Meschia, James F.Mayo Clinic Florida (author)
  • Brown, Devin L.University of Michigan Health System (author)
  • Worrall, Bradford B.University of Virginia Health System (author)
  • Tirschwell, David L.University of Washington (author)
  • Jagiella, Jeremiasz M.Jagiellonian University (author)
  • Schmidt, HelenaMedical University of Graz (author)
  • Jimenez-Conde, JordiAutonomous University of Barcelona,Hospital del Mar Medical Research Institute (author)
  • Fernandez-Cadenas, IsraelAutonomous University of Barcelona,Vall d'Hebron University Hospital (author)
  • Lindgren, ArneLund University,Lunds universitet,Klinisk strokeforskning,Forskargrupper vid Lunds universitet,Clinical Stroke Research Group,Lund University Research Groups,Skåne University Hospital(Swepub:lu)neur-ali (author)
  • Slowik, AgnieszkaJagiellonian University (author)
  • Gill, DipenderImperial College London (author)
  • Holmes, MichaelUniversity of Oxford (author)
  • Phuah, Chia LingWashington University in St. Louis (author)
  • Petersen, Nils H.Yale University (author)
  • Matouk, MD, Charles N.Yale University (author)
  • Gunel, MuratYale University (author)
  • Sansing, LaurenYale University (author)
  • Bennett, DerrickUniversity of Oxford (author)
  • Chen, ZhengmingUniversity of Oxford (author)
  • Sun, Luan L.University of Cambridge (author)
  • Clarke, RobertYale University (author)
  • Walters, Robin G.University of Oxford (author)
  • Gill, Thomas M.Yale University (author)
  • Biffi, AlessandroBroad Institute,Massachusetts General Hospital (author)
  • Kathiresan, SekarBroad Institute,Massachusetts General Hospital (author)
  • Langefeld, Carl D.Wake Forest University (author)
  • Woo, DanielUniversity of Cincinnati (author)
  • Rosand, JonathanMassachusetts General Hospital,Broad Institute (author)
  • Sheth, Kevin N.Yale University (author)
  • Anderson, Christopher D.Broad Institute,Massachusetts General Hospital (author)
  • Yale UniversityMassachusetts General Hospital (creator_code:org_t)
  • International Stroke Genetics Consortium

Related titles

  • In:Annals of Neurology: Wiley88:1, s. 56-660364-51341531-8249

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