Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage

被引：48

作者：

Falcone, Guido J. ^{[1
]}

Kirsch, Elayna ^{[1
]}

Acosta, Julian N. ^{[1
]}

Noche, Rommell B. ^{[1
]}

Leasure, Audrey ^{[1
]}

Marini, Sandro ^{[2
]}

Chung, Jaeyoon ^{[2
]}

Selim, Magdy ^{[3
]}

Meschia, James F. ^{[4
]}

Brown, Devin L. ^{[5
]}

Worrall, Bradford B. ^{[6
]}

Tirschwell, David L. ^{[7
]}

Jagiella, Jeremiasz M. ^{[8
]}

Schmidt, Helena ^{[9
]}

Jimenez-Conde, Jordi ^{[10
,11
]}

Fernandez-Cadenas, Israel ^{[12
,13
]}

Lindgren, Arne ^{[14
,15
]}

Slowik, Agnieszka ^{[8
]}

Gill, Dipender ^{[16
,17
]}

Holmes, Michael ^{[18
,19
,20
]}

Phuah, Chia-Ling ^{[21
]}

Petersen, Nils H. ^{[1
]}

Matouk, Charles N. ^{[22
]}

Gunel, Murat ^{[22
]}

Sansing, Lauren ^{[23
]}

Bennett, Derrick ^{[19
,20
]}

Chen, Zhengming ^{[19
,20
]}

Sun, Luan L. ^{[24
]}

Clarke, Robert ^{[1
]}

Walters, Robin G. ^{[18
,19
,20
]}

Gill, Thomas M. ^{[25
]}

Biffi, Alessandro ^{[2
,26
,27
,28
]}

Kathiresan, Sekar ^{[2
,26
,30
]}

Langefeld, Carl D. ^{[31
]}

Woo, Daniel ^{[32
]}

Rosand, Jonathan ^{[2
,26
,29
,33
]}

Sheth, Kevin N. ^{[1
]}

Anderson, Christopher D. ^{[2
,26
,29
,33
]}

机构：

[1] Yale Sch Med, Dept Neurol, Div Neurocrit Care & Emergency Neurol, New Haven, CT USA

[2] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA

[3] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA

[4] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA

[5] Univ Michigan Hlth Syst, Dept Neurol, Stroke Program, Ann Arbor, MI USA

[6] Univ Virginia Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA

[7] Univ Washington, Harborview Med Ctr, Stroke Ctr, 325 9Th Ave, Seattle, WA 98104 USA

[8] Jagiellonian Univ, Med Coll, Dept Neurol, Krakow, Poland

[9] Med Univ Graz, Inst Mol Biol & Med Biochem, Graz, Austria

[10] Univ Autonoma Barcelona, Hosp Mar, Inst Municipal Invest Med, Dept Neurol,Neurovasc Res Unit, Barcelona, Spain

[11] Univ Autonoma Barcelona, Hosp Mar, Inst Municipal Invest Med, Program Inflammat & Cardiovasc Disorders, Barcelona, Spain

[12] Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Res Lab, Barcelona, Spain

[13] Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Unit, Barcelona, Spain

[14] Lund Univ, Dept Clin Sci Lund Neurol, Lund, Sweden

[15] Skane Univ Hosp, Dept Neurol, Lund, Sweden

[16] Imperial Coll London, Dept Epidemiol & Biostat, London, England

[17] Imperial Coll London, Dept Stroke Med, London, England

[18] Univ Oxford, MRC, Populat Hlth Res Unit, Oxford, England

[19] Univ Oxford, MRC, Populat Hlth Res Unit, Nuffield Dept Populat Hlth,Clin Trial Serv Unit, Oxford, England

[20] Univ Oxford, MRC, Populat Hlth Res Unit, Nuffield Dept Populat Hlth,Epidemiol Studies Unit, Oxford, England

[21] Washington Univ, Sch Med St Louis, Dept Neurol, St Louis, MO 63110 USA

[22] Yale Sch Med, Dept Neurosurg, New Haven, CT USA

[23] Yale Sch Med, Dept Neurol, Div Vasc Neurol & Stroke, New Haven, CT USA

[24] Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England

[25] Yale Sch Med, Dept Internal Med Geriatr Med, New Haven, CT USA

[26] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[27] MGH, Dept Neurol, Div Behav Neurol, Boston, MA USA

[28] MGH, Dept Psychiat, Div Psychiat, Boston, MA USA

[29] MGH, Dept Neurol, Boston, MA USA

[30] MGH, Cardiovasc Dis Prevent Ctr, Boston, MA USA

[31] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27101 USA

[32] Univ Cincinnati, Coll Med, Dept Neurol, Cincinnati, OH USA

[33] MGH, Henry & Allison McCance Ctr Brain Hlth, Boston, MA USA

来源：

ANNALS OF NEUROLOGY | 2020年 / 88卷 / 01期

基金：

英国医学研究理事会; 美国国家卫生研究院; 英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; CHOLESTEROL LEVEL; APOLIPOPROTEIN-B; STATIN THERAPY; STRATIFICATION; METAANALYSIS; DISEASE; STROKE;

D O I：

10.1002/ana.25740

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 x 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

引用

页码：56 / 66

页数：11

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