Genome Research in African-American Scleroderma Patients (GRASP) Study

Fredrick Wigley, MD
Johns Hopkins University
School of Medicine

Francesco Boin, MD
University of California
San Francisco

In collaboration with:

Dan Kastner, MD, PhD
National Human Genome Research Institute

Project Summary:

Dr. Wigley and Dr. Boin: There is evidence that racial differences exist in the susceptibility to and severity of systemic sclerosis. African Americans have a higher age-specific incidence and prevalence of scleroderma compared to European Americans. The incidence of severe scleroderma-associated interstitial lung disease (SSc-ILD) and pulmonary hypertension (high blood pressure between the heart and lung; a life-threatening complication in scleroderma) is reported to be higher in African Americans than in other ethnic groups. Disease severity is greater and, as a consequence, the disease burden as measured by morbidity and mortality is greater in African Americans. Socioeconomic factors and impaired access to health care do not fully account for the predilection of African American scleroderma patients to poor health outcomes. To date, attempts to elucidate the factors influencing increased disease severity have been hindered by the relatively small size of available African American scleroderma studies.

The Genome Research in African American Scleroderma Patients (GRASP) project was established to enhance our understanding of the clinical phenotype of scleroderma in African Americans and to perform genomic analyses with the aim of identifying factors contributing to the cause(s) and severity of their disease. In order to achieve these goals, a large cohort of African American scleroderma patients has been identified and clinical data as well as biological samples have been collected from enrolled patients.

The GRASP cohort currently consists of more than 1,200 extensively evaluated African American scleroderma patients enrolled from 23 participating U.S. academic centers. It is the largest multicenter cohort of African American scleroderma patients; consequently, GRASP’s comprehensive clinical database and the significant size of the cohort enable informative analyses; including, in our initial phase, careful description of clinical features and the analysis of samples from these patients to understand the biology of the disease. Our initial study (in press) emphasizes the unique and severe disease burden of scleroderma in African Americans and highlights factors associated with clinically significant manifestations of scleroderma in African Americans.

The GRASP consortium is now working to define how variation in the DNA across the genome of African American patients may affect the expression of scleroderma. Subtle and rare differences between the DNA makeup of African Americans who have scleroderma and African Americans not affected by the disease or other ethnic populations may explain their increased risk of developing scleroderma as well as its severe clinical manifestations.

How This Work Will Impact Patients:

One of the challenges of caring and managing a complex multisystem disease like scleroderma is to be able to define not only its stage of disease activity, but to be able to predict the future course of the disease in an individual. We know that scleroderma does not follow one well-defined path; rather, every patient is unique and disease manifestations are highly variable. The heterogeneous disease expression (mild in some and severe in others) needs to be understood in order to guide physicians to the best treatment for an individual patient. We hope that the GRASP project will provide novel insights into the basis for disease expression in African Americans by discovering specific genes or genetic areas that associate with a specific clinical picture. This would allow clinicians to identify individuals at risk for certain outcomes, to follow those patients closely, and to intervene with therapies at the appropriate moment.

The GRASP project will have a major impact not only in helping us understand and manage African Americans with scleroderma, but also it will have an impact on scleroderma patients of other racial backgrounds. Because GRASP will likely identify genes associated with scleroderma and with specific manifestations of the disease, it also provides an incredible opportunity for novel studies of the disease process and the underlying biological processes that cause the disease to occur and progress.

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