Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity: A Meta-analysis.
Marini S., Crawford K., Morotti A., Lee MJ., Pezzini A., Moomaw CJ., Flaherty ML., Montaner J., Roquer J., Jimenez-Conde J., Giralt-Steinhauer E., Elosua R., Cuadrado-Godia E., Soriano-Tarraga C., Slowik A., Jagiella JM., Pera J., Urbanik A., Pichler A., Hansen BM., McCauley JL., Tirschwell DL., Selim M., Brown DL., Silliman SL., Worrall BB., Meschia JF., Kidwell CS., Testai FD., Kittner SJ., Schmidt H., Enzinger C., Deary IJ., Rannikmae K., Samarasekera N., Salman RA-S., Sudlow CL., Klijn CJM., van Nieuwenhuizen KM., Fernandez-Cadenas I., Delgado P., Norrving B., Lindgren A., Goldstein JN., Viswanathan A., Greenberg SM., Falcone GJ., Biffi A., Langefeld CD., Woo D., Rosand J., Anderson CD., International Stroke Genetics Consortium None.
Importance: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) ε4 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 ε2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P