Dataset Information

19th Workshop of the International Stroke Genetics Consortium, April 28-29, 2016, Boston, Massachusetts, USA: 2016.001 MRI-defined cerebrovascular genomics-The CHARGE consortium.

ABSTRACT: The CHARGE consortium is an investigator-initiated collaboration to facilitate meta-analyses of genome-wide association studies (GWAS) and genomic analyses based on next generation sequencing (NGS), among multiple large and well-phenotyped population-based cohort studies around the world (http://www.chargeconsortium.com). Within the neuro-CHARGE working group, we are presenting an update of ongoing genomic studies on MRI-markers of cerebrovascular disease. Large population-based studies have shown that the burden of cerebrovascular disease extends far beyond that of clinical stroke. MRI-markers of cerebral small vessel disease, such as white matter hyperintensities (WMH), small subcortical brain infarcts, microbleeds, or dilated perivascular spaces, are particularly frequent in older community persons. These markers portend an increased risk of stroke, dementia, and premature death, and were shown to have a high heritability, especially WMH burden. Interestingly recent work has revealed genetic risk variants between WMH burden and stroke. To account for the major role of high blood pressure in the occurrence of WMH, we are performing a GWAS of WMH burden stratified on hypertension status, as well as a joint meta-analysis to account for gene-environment interaction with hypertension. Moreover, based on prior epidemiologic and histologic data suggesting that the pathogenesis of WMH may differ according to their location, we are running separate GWAS for periventricular and deep WMH burden. A GWAS of cerebral microbleeds is being finalized. We are also exploring the role of vascular risk factors in the occurrence of dementia by examining the relation of genetic risk scores for these factors with MRI-markers of brain aging and cerebrovascular disease. Finally, several NGS projects are being conducted to identify rare variants associated with WMH burden and lacunar brain infarcts. Additional projects are also currently being designed, including GWAS of novel MRI phenotypes, such as composite measures of cerebral small vessel disease, as well as lifetime, and epigenomic approaches.

SUBMITTER: Debette S

PROVIDER: S-EPMC5390739 | biostudies-other | 2017 Mar

REPOSITORIES: biostudies-other

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Project description:ImportancePrevious studies have shown high mortality rates among homeless people in general, but little is known about the patterns of mortality among "rough sleepers," the subgroup of unsheltered urban homeless people who avoid emergency shelters and primarily sleep outside.ObjectivesTo assess the mortality rates and causes of death for a cohort of unsheltered homeless adults from Boston, Massachusetts.Design, setting, and participantsA 10-year prospective cohort study (2000-2009) of 445 unsheltered homeless adults in Boston, Massachusetts, who were seen during daytime street and overnight van clinical visits performed by the Boston Health Care for the Homeless Program's Street Team during 2000. Data used to describe the unsheltered homeless cohort and to document causes of death were gathered from clinical encounters, medical records, the National Death Index, and the Massachusetts Department of Public Health death occurrence files. The study data set was linked to the death occurrence files by using a probabilistic record linkage program to confirm the deaths. Data analysis was performed from May 1, 2015, to September 6, 2016.ExposureBeing unsheltered in an urban setting.Main outcomes and measuresAge-standardized all-cause and cause-specific mortality rates and age-stratified incident rate ratios that were calculated for the unsheltered adult cohort using 2 comparison groups: the nonhomeless Massachusetts adult population and an adult homeless cohort from Boston who slept primarily in shelters.ResultsOf 445 unsheltered adults in the study cohort, the mean (SD) age at enrollment was 44 (11.4) years, 299 participants (67.2%) were non-Hispanic white, and 72.4% were men. Among the 134 individuals who died, the mean (SD) age at death was 53 (11.4) years. The all-cause mortality rate for the unsheltered cohort was almost 10 times higher than that of the Massachusetts population (standardized mortality rate, 9.8; 95% CI, 8.2-11.5) and nearly 3 times higher than that of the adult homeless cohort (standardized mortality rate, 2.7; 95% CI, 2.3-3.2). Non-Hispanic black individuals had more than half the rate of death compared with non-Hispanic white individuals, with a rate ratio of 0.4 (95% CI, 0.2-0.7; P < .001). The most common causes of death were noncommunicable diseases (eg, cancer and heart disease), alcohol use disorder, and chronic liver disease.Conclusions and relevanceMortality rates for unsheltered homeless adults in this study were higher than those for the Massachusetts adult population and a sheltered adult homeless cohort with equivalent services. This study suggests that this distinct subpopulation of homeless people merits special attention to meet their unique clinical and psychosocial needs.

Dataset Information

19th Workshop of the International Stroke Genetics Consortium, April 28-29, 2016, Boston, Massachusetts, USA: 2016.001 MRI-defined cerebrovascular genomics-The CHARGE consortium.

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