17p12 Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage

作者：Sandro Marini, William J. Devan, Farid Radmanesh, Laura C. Miyares, Timothy Poterba, Björn M. Hansen, Bo Norrving, Jordi Jiménez-Conde, Eva Giralt Steinhauer, Roberto Elosúa, Elisa Cuadrado‐Godia, Carolina Soriano‐Tárraga, Jaume Roquer, Christina E. Kourkoulis, Alison M. Ayres, Kristin M. Schwab, David Tirschwell, Magdy H. Selim, Devin L. Brown, Scott L. Silliman, Bradford B. Worrall, James F. Meschia, Chelsea S. Kidwell, Joan Montaner, Israel Fernández‐Cadenas, Pilar Delgado, Steven Mark Greenberg, Arne G. Lindgren, Charles Matouk, Kevin Navin Sheth, Daniel Woo, Christopher D. Anderson, Jonathan M. Rosand, Guido J. Falcone · 发表于：Stroke · 年份：2018 · DOI：10.1161/strokeaha.117.020091 · 被引用次数：30 · 研究领域：Intracerebral and Subarachnoid Hemorrhage Research、Intracranial Aneurysms: Treatment and Complications、Neuroinflammation and Neurodegeneration Mechanisms

Background and Purpose— 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. Methods— 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. Results— 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 replic...