Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity: A Meta-analysis
AuthorKidwell, Chelsea S
AffiliationUniv Arizona, Dept Neurol
MetadataShow full item record
PublisherAMER MEDICAL ASSOC
CitationMarini S, Crawford K, Morotti A, et al. Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity: A Meta-analysis. JAMA Neurol. Published online February 06, 201976(4):480–491. doi:10.1001/jamaneurol.2018.4519
Rights© 2019 Marini S et al. JAMA Neurology. This is an open access article distributed under the terms of the CC-BY License.
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AbstractIMPORTANCE Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. OBJECTIVE To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) epsilon 4 alleles, the most potent genetic risk factor for ICH. DESIGN, SETTING, AND PARTICIPANTS This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. MAIN OUTCOMES AND MEASURES Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. RESULTS In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE epsilon 2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P < .001) and APOE epsilon 4 (OR, 1.51; 95% CI, 1.23-1.85; P < .001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE epsilon 4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants. APOE epsilon 2 and epsilon 4 did not show an association with nonlobar ICH risk in any race/ethnicity. CONCLUSIONS AND RELEVANCE APOE epsilon 4 and epsilon 2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.
NoteOpen access article
VersionFinal published version
SponsorsNIH National Institute of Neurological Disorders and Stroke [K23NS086873, R01NS103924, U01NS069763, R01NS093870, R01AG047975, R01AG026484, P50AG005134, K23AG02872605]; Yale Pepper Scholar Award [P30AG021342]; Neurocritical Care Society Research Fellowship; American Heart Association fellowship [18POST34080063]; United Kingdom Medical Research Council/Stroke Association Clinical Research Training Fellowship; United Kingdom Medical Research Council Senior Clinical Fellowship; Age UK (The Disconnected Mind project); Medical Research Council [MR/M01311/1]; Centre for Cognitive Ageing and Cognitive Epidemiology - Medical Research Council [MR/K026992/1]; Centre for Cognitive Ageing and Cognitive Epidemiology - Biotechnology and Biological Sciences Research Council [MR/K026992/1]; Wellcome Trust; Binks Trust; Scottish Funding Council; Chief Scientist Office; Swedish Heart and Lung Foundation; Region Skane; Skane University Hospital; Freemasons Lodge of Instruction EOS in Lund; King Gustaf V and Queen Victoria's Foundation; Lund University; Foundation of Fars & Frosta (one of Sparbanken Skane's ownership Foundations); Swedish Stroke Association; Spain Ministry of Health Instituto de Salud Carlos III [FEDER RD16/0019/0002]
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