Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage
| Autor: | Dipender Gill, Arne Lindgren, Michael V. Holmes, Carl D. Langefeld, Devin L. Brown, Christopher D. Anderson, Daniel Woo, Derrick A Bennett, Alessandro Biffi, Jaeyoon Chung, James F. Meschia, Jordi Jimenez-Conde, Nils H Petersen, Thomas M. Gill, Bradford B. Worrall, Elayna Kirsch, Jonathan Rosand, Jeremiasz M. Jagiella, Israel Fernandez-Cadenas, David L. Tirschwell, Audrey C Leasure, Robin G. Walters, Sekar Kathiresan, Murat Gunel, Robert Clarke, Julian N Acosta, Zhengming Chen, Sandro Marini, Chia-Ling Phuah, Lauren H Sansing, C. Matouk, Kevin N. Sheth, Helena Schmidt, Magdy Selim, Agnieszka Slowik, Luan Luan Sun, Rommell B Noche, Guido J. Falcone |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Single-nucleotide polymorphism Lower risk Polymorphism Single Nucleotide Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Mendelian randomization medicine Humans Genetic Predisposition to Disease Stroke Triglycerides Aged Cerebral Hemorrhage Aged 80 and over Intracerebral hemorrhage Cholesterol business.industry Cholesterol HDL Cholesterol LDL Middle Aged medicine.disease 030104 developmental biology Endocrinology Neurology chemistry Female lipids (amino acids peptides and proteins) Polygenic risk score Neurology (clinical) business 030217 neurology & neurosurgery Genome-Wide Association Study Lipoprotein |
| Zdroj: | Annals of Neurology Ann Neurol |
| ISSN: | 0364-5134 |
| DOI: | 10.1002/ana.25740 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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