Dataset Information

17p12 Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage.

ABSTRACT:

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.

SUBMITTER: Marini S

PROVIDER: S-EPMC6085089 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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<i>17p12</i> Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage.

Marini Sandro S Devan William J WJ Radmanesh Farid F Miyares Laura L Poterba Timothy T Hansen Björn M BM Norrving Bo B Jimenez-Conde Jordi J Giralt-Steinhauer Eva E Elosua Roberto R Cuadrado-Godia Elisa E Soriano Carolina C Roquer Jaume J Kourkoulis Christina E CE Ayres Alison M AM Schwab Kristin K Tirschwell David L DL Selim Magdy M Brown Devin L DL Silliman Scott L SL Worrall Bradford B BB Meschia James F JF Kidwell Chelsea S CS Montaner Joan J Fernandez-Cadenas Israel I Delgado Pilar P Greenberg Steven M SM Lindgren Arne A Matouk Charles C Sheth Kevin N KN Woo Daniel D Anderson Christopher D CD Rosand Jonathan J Falcone Guido J GJ

Stroke 20180618 7

<h4>Background and purpose</h4>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.<h4>Methods</h4>We conducted a 2-stage (discovery and replication) case-only genome-wide association study in patients with ICH of European ancestry. We utilized the admi ...[more]

PMID: 29915124

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