Articles: phenotype.
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Multicenter Study
Phenotyping Stroke in Sub-Saharan Africa: Stroke Investigative Research and Education Network (SIREN) Phenomics Protocol.
As the second leading cause of death and the leading cause of adult-onset disability, stroke is a major public health concern particularly pertinent in Sub-Saharan Africa (SSA), where nearly 80% of all global stroke mortalities occur, and stroke burden is projected to increase in the coming decades. However, traditional and emerging risk factors for stroke in SSA have not been well characterized, thus limiting efforts at curbing its devastating toll. The Stroke Investigative Research and Education Network (SIREN) project is aimed at comprehensively evaluating the key environmental and genomic risk factors for stroke (and its subtypes) in SSA while simultaneously building capacities in phenomics, biobanking, genomics, biostatistics, and bioinformatics for brain research. ⋯ SIREN is a transnational, multicentre, hospital and community-based study involving 3,000 cases and 3,000 controls recruited from 8 sites in Ghana and Nigeria. Cases will be hospital-based patients with first stroke within 10 days of onset in whom neurovascular imaging will be performed. Etiological and topographical stroke subtypes will be documented for all cases. Controls will be hospital- and community-based participants, matched to cases on the basis of gender, ethnicity, and age (±5 years). Information will be collected on known and proposed emerging risk factors for stroke. STUDY SIGNIFICANCE: SIREN is the largest study of stroke in Africa to date. It is anticipated that it will shed light on the phenotypic characteristics and risk factors of stroke and ultimately provide evidence base for strategic interventions to curtail the burgeoning burden of stroke on the sub-continent.
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Int J Chron Obstruct Pulmon Dis · Jan 2015
Multicenter Study Comparative Study Observational StudyIs a previous diagnosis of asthma a reliable criterion for asthma-COPD overlap syndrome in a patient with COPD?
Some patients share characteristics of both COPD and asthma. As yet, there is no gold standard to identify patients with the so-called asthma-COPD overlap syndrome (ACOS). ⋯ ACOS patients diagnosed on the basis of a previous diagnosis of asthma differed from the remaining COPD patients, but they were similar to ACOS patients diagnosed according to more restrictive criteria, suggesting that a history of asthma before the age of 40 years could be a useful criterion to suspect ACOS in a patient with COPD.
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Multicenter Study
Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm.
Genetic risk factors for intracranial aneurysm (IA) are not yet fully understood. Genomewide association studies have been successful at identifying common variants; however, the role of rare variation in IA susceptibility has not been fully explored. In this study, we report the use of whole exome sequencing (WES) in seven densely-affected families (45 individuals) recruited as part of the Familial Intracranial Aneurysm study. ⋯ We demonstrate that sequencing of densely affected families permits exploration of the role of rare variants in a relatively common disease such as IA, although there are important study design considerations for applying sequencing to complex disorders. In this study, we explore methods of WES variant prioritization, including the incorporation of unaffected individuals, multipoint linkage analysis, biological pathway information, and transcriptome profiling. Further studies are needed to validate and characterize the set of variants and genes identified in this study.
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J. Am. Coll. Cardiol. · Aug 2014
Randomized Controlled Trial Multicenter StudyCardiovascular phenotype in HFpEF patients with or without diabetes: a RELAX trial ancillary study.
The RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction) study was a multicenter, randomized trial of sildenafil versus placebo in heart failure with preserved ejection fraction (HFpEF) with rigorous entry criteria and extensive phenotypic characterization of participants. ⋯ HFpEF patients with diabetes are at increased risk of hospitalization and have reduced exercise capacity. Multimorbidity, impaired chronotropic reserve, left ventricular hypertrophy, and activation of inflammatory, pro-oxidative, vasoconstrictor, and profibrotic pathways may contribute to adverse outcomes in HFpEF patients with diabetes. (Evaluating the Effectiveness of Sildenafil at Improving Health Outcomes and Exercise Ability in People With Diastolic Heart Failure [The RELAX Study]; NCT00763867).
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J. Allergy Clin. Immunol. · May 2014
Multicenter Study Clinical TrialUnsupervised phenotyping of Severe Asthma Research Program participants using expanded lung data.
Previous studies have identified asthma phenotypes based on small numbers of clinical, physiologic, or inflammatory characteristics. However, no studies have used a wide range of variables using machine learning approaches. ⋯ The unsupervised machine learning approaches used here provide unique insights into disease, confirming other approaches while revealing novel additional phenotypes.