Verhaaren B.F.J.,University of Texas Health Science Center at Houston |
Smith J.A.,Medical Informatics |
Ikram M.K.,Internal Medicine |
Adams H.H.,Clinical Chemistry |
And 81 more authors.
Circulation: Cardiovascular Genetics | Year: 2015
Background-The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. Methods and Results-We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10-19) and identified novel loci on chr10q24 (P=1.6×10-9) and chr2p21 (P=4.4×10-8). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10-8) and chr2p16 (P=1.5×10-8). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). Conclusions-We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms. © 2015 American Heart Association, Inc.
Samarasekera N.,University of Edinburgh |
Fonville A.,University of Edinburgh |
Lerpiniere C.,University of Edinburgh |
Farrall A.J.,University of Edinburgh |
And 161 more authors.
Stroke | Year: 2015
BACKGROUND AND PURPOSE - : The characteristics of intracerebral hemorrhage (ICH) may vary by ICH location because of differences in the distribution of underlying cerebral small vessel diseases. Therefore, we investigated the incidence, characteristics, and outcome of lobar and nonlobar ICH. METHODS - : In a population-based, prospective inception cohort study of ICH, we used multiple overlapping sources of case ascertainment and follow-up to identify and validate ICH diagnoses in 2010 to 2011 in an adult population of 695 335. RESULTS - : There were 128 participants with first-ever primary ICH. The overall incidence of lobar ICH was similar to nonlobar ICH (9.8 [95% confidence interval, 7.7-12.4] versus 8.6 [95% confidence interval, 6.7-11.1] per 100 000 adults/y). At baseline, adults with lobar ICH were more likely to have preceding dementia (21% versus 5%; P=0.01), lower Glasgow Coma Scale scores (median, 13 versus 14; P=0.03), larger ICHs (median, 38 versus 11 mL; P<0.001), subarachnoid extension (57% versus 5%; P<0.001), and subdural extension (15% versus 3%; P=0.02) than those with nonlobar ICH. One-year case fatality was lower after lobar ICH than after nonlobar ICH (adjusted odds ratio for death at 1 year: lobar versus nonlobar ICH 0.21; 95% confidence interval, 0.07-0.63; P=0.006, after adjustment for known predictors of outcome). There were 4 recurrent ICHs, which occurred exclusively in survivors of lobar ICH (annual risk of recurrent ICH after lobar ICH, 11.8%; 95% confidence interval, 4.6%-28.5% versus 0% after nonlobar ICH; log-rank P=0.04). CONCLUSIONS - : The baseline characteristics and outcome of lobar ICH differ from other locations. © 2015 American Heart Association, Inc.
Subedi D.,Royal Infirmary |
Zishan U.S.,Royal Infirmary |
Chappell F.,University of Edinburgh |
Gregoriades M.-L.,Royal Infirmary |
And 5 more authors.
Stroke | Year: 2015
Background and Purpose - Intracranial internal carotid artery calcification is associated with cerebrovascular risk factors and stroke, but few quantification methods are available. We tested the reliability of visual scoring, semiautomated Agatston score, and calcium volume measurement in patients with recent stroke. Methods - We used scans from a prospective hospital stroke registry and included patients with anterior circulation ischemic stroke or transient ischemic stroke whose noncontrast cranial computed tomographic scans were available electronically. Two raters measured semiautomatic quantitative Agatston score, and calcium volume, and performed qualitative visual scoring using the original 4-point Woodcock score and a modified Woodcock score, where each image on which the internal carotid arteries appeared was scored and the slice scores summed. Results - Intra- and interobserver coefficient of variations were 8.8% and 16.5% for Agatston, 8.8% and 15.5% for calcium volume, and 5.7% and 5.4% for the modified Woodcock visual score, respectively. The modified Woodcock visual score correlated strongly with both Agatston and calcium volume quantitative measures (both R2=0.84; P<0.0001); calcium volume increased by 0.47-mm/point increase in modified Woodcock visual score. Intracranial internal carotid artery calcification increased with age by all measures (eg, visual score, Spearman ρ=0.4; P=0.005). Conclusions - Visual scores correlate highly with quantitative intracranial internal carotid artery calcification measures, with excellent observer agreements. Visual intracranial internal carotid artery scores could be a rapid and practical method for epidemiological studies. © 2015 American Heart Association, Inc.