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Front Neurol. 2018 Jul 6;9:514. doi: 10.3389/fneur.2018.00514. eCollection 2018.

Comparison of Genetic and Self-Identified Ancestry in Modeling Intracerebral Hemorrhage Risk.

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Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States.
Medical and Population Genetics, Broad Institute, Cambridge, MA, United States.
Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Department of Neurology and Rehabilitation, University of Illinois College of Medicine, Chicago, IL, United States.
Department of Neurology, Baltimore Veterans Administration Medical Center and University of Maryland School of Medicine, Baltimore, MD, United States.
Departments of Anesthesiology and Neurology, Brain Injury Translational Research Center, Duke University, Durham, NC, United States.
Center for Public Health Genomics and Department of Biostatistical Sciences, Wake Forest University, Winston-Salem, NC, United States.
J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston, MA, United States.


Background: We sought to determine whether a small pool of ancestry-informative DNA markers (AIMs) improves modeling of intracerebral hemorrhage (ICH) risk in heterogeneous populations, compared with self-identified race/ethnicity (SIRE) alone. Methods: We genotyped 15 preselected AIMs to perform principal component (PC) analysis in the ERICH study (a multi-center case-control study of ICH in whites, blacks, and Hispanics). We used multivariate logistic regression and tests for independent samples to compare associations for genetic ancestry and SIRE with ICH-associated vascular risk factors (VRFs). We then compared the performance of models for ICH risk that included AIMs and SIRE alone. Results: Among 4,935 subjects, 34.7% were non-Hispanic black, 35.1% non-Hispanic white, and 30.2% Hispanic by SIRE. In stratified analysis of these SIRE groups, AIM-defined ancestry was strongly associated with seven of the eight VRFs analyzed (p < 0.001). Within each SIRE group, regression of AIM-derived PCs against VRFs confirmed independent associations of AIMs across at least two race/ethnic groups for seven VRFs. Akaike information criterion (AIC) (6,294 vs. 6,286) and likelihood ratio test (p < 0.001) showed that genetic ancestry defined by AIMs achieved a better ICH risk modeling compared to SIRE alone. Conclusion: Genetically-defined ancestry provides valuable risk exposure information that is not captured by SIRE alone. Particularly among Hispanics and blacks, inclusion of AIMs adds value over self-reported ancestry in controlling for genetic and environmental exposures that influence risk of ICH. While differences are small, this modeling approach may be superior in highly heterogeneous clinical poulations. Additional studies across other ancestries and risk exposures are needed to confirm and extend these findings.


genetics; genetics population; intracranial hemorrhage; precision medicine; race and ethnicity; risk factors; vascular diseases

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