Citations 2
Genome-Wide Association Study of Hematoma Volume Identifies 17p12 as a Novel Susceptibility Locus for Severity and Outcome in Intracerebral Hemorrhage (S1.002)
Devan, William J., Miyares, Laura , Poterba, Timothy , Jiménez-Conde, Jordi , González, Jaume Roquer, Kourkoulis, Christina , Silliman, Scott, Worrall, Bradford B. , Kidwell, Chelsea S., Greenberg, Steven M. , Matouk, Charles, Woo, Daniel , Falcone, Guido J. , Marini, Sandro , Radmanesh, Farid , Hansen, Björn M. , Norrving, Bo , Giralt‐Steinhauer, Eva , Elosúa, Roberto , Cuadrado‐Godia, Elisa , Soriano‐Tárraga, Carolina , Ayres, Alison M. , Schwab, Kristin , Tirschwell, David , Selim, Magdy H. , Brown, Devin L. , Meschia, James F. , Montaner, Joan , Fernández‐Cadenas, Israel , Delgado, Pilar , Lindgren, Arne G. , Sheth, Kevin N. , Anderson, Christopher D. , Rosand, Jonathan M.
Neurology | December 7, 2023 | Volume: 90 | Issue: 15_supplement | Pages: No page available
17p12 Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage
Devan, William J., Radmanesh, Farid , Miyares, Laura , Poterba, Timothy , Hansen, Björn M. , Jiménez-Conde, Jordi , Elosúa, Roberto , Cuadrado‐Godia, Elisa , Soriano‐Tárraga, Carolina , Roquer, Jaume , Kourkoulis, Christina , Schwab, Kristin , Tirschwell, David , Brown, Devin L. , Silliman, Scott, Worrall, Bradford B. , Kidwell, Chelsea S., Montaner, Joan , Delgado, Pilar , Greenberg, Steven M. , Matouk, Charles, Woo, Daniel , Anderson, Christopher D. , Falcone, Guido J. , Montaner, Joan , Marini, Sandro , Norrving, Bo , Giralt‐Steinhauer, Eva , Ayres, Alison M. , Selim, Magdy H. , Meschia, James F. , Fernández‐Cadenas, Israel , Lindgren, Arne G. , Sheth, Kevin N. , Rosand, Jonathan M.
Stroke | June 18, 2018 | Volume: 49 | Issue: 7 | Pages: 1618-1625
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 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). Conclusions— 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.