Title |
17p12 Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage
|
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Published in |
Stroke, June 2018
|
DOI | 10.1161/strokeaha.117.020091 |
Pubmed ID | |
Authors |
Sandro Marini, William J Devan, Farid Radmanesh, Laura Miyares, Timothy Poterba, Björn M Hansen, Bo Norrving, Jordi Jimenez-Conde, Eva Giralt-Steinhauer, Roberto Elosua, Elisa Cuadrado-Godia, Carolina Soriano, Jaume Roquer, Christina E Kourkoulis, Alison M Ayres, Kristin Schwab, David L Tirschwell, Magdy Selim, Devin L Brown, Scott L Silliman, Bradford B Worrall, James F Meschia, Chelsea S Kidwell, Joan Montaner, Israel Fernandez-Cadenas, Pilar Delgado, Steven M Greenberg, Arne Lindgren, Charles Matouk, Kevin N Sheth, Daniel Woo, Christopher D Anderson, Jonathan Rosand, Guido J Falcone |
Abstract |
Hematoma volume is an important determinant of clinical outcome in spontaneous intracerebral hemorrhage (ICH). We performed a genome-wide association study (GWAS) of hematoma volume with the aim of identifying novel biological pathways involved in the pathophysiology of primary brain injury in ICH. We conducted a 2-stage (discovery and replication) case-only genome-wide association study in patients with ICH of European ancestry. We utilized the admission head computed tomography to calculate hematoma volume via semiautomated computer-assisted technique. After quality control and imputation, 7 million genetic variants were available for association testing with ICH volume, which was performed separately in lobar and nonlobar ICH cases using linear regression. Signals with P<5×10-8 were pursued in replication and tested for association with admission Glasgow coma scale and 3-month post-ICH dichotomized (0-2 versus 3-6) modified Rankin Scale using ordinal and logistic regression, respectively. The discovery phase included 394 ICH cases (228 lobar and 166 nonlobar) and identified 2 susceptibility loci: a genomic region on 22q13 encompassing PARVB (top single-nucleotide polymorphism rs9614326: β, 1.84; SE, 0.32; P=4.4×10-8) for lobar ICH volume and an intergenic region overlying numerous copy number variants on 17p12 (top single-nucleotide polymorphism rs11655160: β, 0.95; SE, 0.17; P=4.3×10-8) for nonlobar ICH volume. The replication included 240 ICH cases (71 lobar and 169 nonlobar) and corroborated the association for 17p12 (P=0.04; meta-analysis P=2.5×10-9; heterogeneity, P=0.16) but not for 22q13 (P=0.49). In multivariable analysis, rs11655160 was also associated with lower admission Glasgow coma scale (odds ratio, 0.17; P=0.004) and increased risk of poor 3-month modified Rankin Scale (odds ratio, 1.94; P=0.045). We identified 17p12 as a novel susceptibility risk locus for hematoma volume, clinical severity, and functional outcome in nonlobar ICH. Replication in other ethnicities and follow-up translational studies are needed to elucidate the mechanism mediating the observed association. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 21% |
United Kingdom | 2 | 14% |
France | 1 | 7% |
Brazil | 1 | 7% |
Spain | 1 | 7% |
Unknown | 6 | 43% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 12 | 86% |
Scientists | 1 | 7% |
Practitioners (doctors, other healthcare professionals) | 1 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 45 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 8 | 18% |
Student > Ph. D. Student | 4 | 9% |
Student > Doctoral Student | 4 | 9% |
Professor | 4 | 9% |
Student > Bachelor | 4 | 9% |
Other | 11 | 24% |
Unknown | 10 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 13 | 29% |
Neuroscience | 5 | 11% |
Nursing and Health Professions | 4 | 9% |
Biochemistry, Genetics and Molecular Biology | 3 | 7% |
Psychology | 2 | 4% |
Other | 5 | 11% |
Unknown | 13 | 29% |