Document Detail

Variants at APOE influence risk of deep and lobar intracerebral hemorrhage.
MedLine Citation:
PMID:  21061402     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Prior studies investigating the association between APOE alleles ε2/ε4 and risk of intracerebral hemorrhage (ICH) have been inconsistent and limited to small sample sizes, and did not account for confounding by population stratification or determine which genetic risk model was best applied.
METHODS: We performed a large-scale genetic association study of 2189 ICH cases and 4041 controls from 7 cohorts, which were analyzed using additive models for ε2 and ε4. Results were subsequently meta-analyzed using a random effects model. A proportion of the individuals (322 cases, 357 controls) had available genome-wide data to adjust for population stratification.
RESULTS: Alleles ε2 and ε4 were associated with lobar ICH at genome-wide significance levels (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.50-2.23, p = 6.6 × 10(-10); and OR = 2.20, 95%CI = 1.85-2.63, p = 2.4 × 10(-11), respectively). Restriction of analysis to definite/probable cerebral amyloid angiopathy ICH uncovered a stronger effect. Allele ε4 was also associated with increased risk for deep ICH (OR = 1.21, 95% CI = 1.08-1.36, p = 2.6 × 10(-4)). Risk prediction evaluation identified the additive model as best for describing the effect of APOE genotypes.
INTERPRETATION: APOE ε2 and ε4 are independent risk factors for lobar ICH, consistent with their known associations with amyloid biology. In addition, we present preliminary findings on a novel association between APOE ε4 and deep ICH. Finally, we demonstrate that an additive model for these APOE variants is superior to other forms of genetic risk modeling previously applied.
Alessandro Biffi; Akshata Sonni; Christopher D Anderson; Brett Kissela; Jeremiasz M Jagiella; Helena Schmidt; Jordi Jimenez-Conde; Björn M Hansen; Israel Fernandez-Cadenas; Lynelle Cortellini; Alison Ayres; Kristin Schwab; Karol Juchniewicz; Andrzej Urbanik; Natalia S Rost; Anand Viswanathan; Thomas Seifert-Held; Eva-Maria Stoegerer; Marta Tomás; Raquel Rabionet; Xavier Estivill; Devin L Brown; Scott L Silliman; Magdy Selim; Bradford B Worrall; James F Meschia; Joan Montaner; Arne Lindgren; Jaume Roquer; Reinhold Schmidt; Steven M Greenberg; Agnieszka Slowik; Joseph P Broderick; Daniel Woo; Jonathan Rosand;
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of neurology     Volume:  68     ISSN:  1531-8249     ISO Abbreviation:  Ann. Neurol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2011-01-03     Completed Date:  2011-01-31     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  7707449     Medline TA:  Ann Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  934-43     Citation Subset:  IM    
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MeSH Terms
African Americans
Aged, 80 and over
Apolipoprotein E2 / genetics*
Apolipoprotein E4 / genetics*
Cerebral Amyloid Angiopathy
Cerebral Hemorrhage / epidemiology,  genetics*,  radiography
Cohort Studies
Cross-Cultural Comparison
European Continental Ancestry Group
Gene Frequency
Genetic Predisposition to Disease*
Genetic Variation / genetics*
Genome-Wide Association Study
Meta-Analysis as Topic
Middle Aged
Models, Genetic
Principal Component Analysis
Risk Factors
Grant Support
5R01NS042147/NS/NINDS NIH HHS; K23 NS042695/NS/NINDS NIH HHS; K23 NS042695-05/NS/NINDS NIH HHS; K23 NS064052/NS/NINDS NIH HHS; K23NS042695/NS/NINDS NIH HHS; M01 RR000042/RR/NCRR NIH HHS; NS30678/NS/NINDS NIH HHS; NS36695/NS/NINDS NIH HHS; P 20545-B05//Austrian Science Fund FWF; R01 NS059727/NS/NINDS NIH HHS; R01 NS059727-02/NS/NINDS NIH HHS; R01NS059727/NS/NINDS NIH HHS
Reg. No./Substance:
0/Apolipoprotein E2; 0/Apolipoprotein E4

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