Approved Research

Characterizing the phenotypic spectrum of sickle cell disease patients and individuals with sickle cell trait using deep phenotyping and genomic data

Lay summary

Scientific rationale: this study aims to further our understanding of the genetic basis of variation in blood traits between individuals. While some blood traits such as hemoglobin levels or red blood cell counts are routinely monitored for overall health status, variation in these traits may also help us understand the biological underpinnings of many inherited blood disorders such as sickle cell disease (SCD). SCD is a common inherited blood disorder that disproportionately affects individuals of African ancestries. There is significant variation in clinical presentation and treatment response of patients with SCD. Due to a paucity of medical and genetic data in underserved communities, our understanding of the full spectrum of the medical symptoms and lab measurements in SCD patients and those at risk for SCD related medical complications is incomplete. We aim to study the impact of genetic variation in blood traits on health outcomes in individuals with SCD and those without SCD. 

Aims: we will catalogue the full extent of medical symptoms in SCD patients in the UK Biobank cohort using extensive electronic medical records, blood measurements from different time points, lifestyle and genetic data. We will investigate the impact of genetic differences between individuals on differences in their health outcomes including SCD or its common complications such as kidney failure, lung problems and stroke. This will help us identify lab measurements that can predict the disease severity or progression to inform patient management.

Project duration: this study aims to heavily utilize the DNA sequencing data linked to long-term health outcomes and lab measurements, which will be released with rolling updates. Therefore, we estimate the project duration to be three years. We are fully committed to sharing our research findings with the scientific community and making our results publicly available in accordance with the annual update requirement.

Public health impact: SCD is a devastating blood disorder characterized by chronic severe anemia that can lead to a wide spectrum of end organ damages. There are approximately 15,000 people in the UK with SCD, more than 350,000 babies are born each year all over the world with SCD. These patients suffer ~30-year reduction in life expectancy due to SCD and its complications. SCD presents an urgent unmet need in underserved communities. We believe the large-scale UK Biobank data will provide genetic insights into blood traits resulting in better understanding of red blood cell health and treatment opportunities for these patients.