GRASP Project

About the Genome Research in African American Scleroderma Patients (GRASP) Project

Project Leadership

Fredrick Wigley, MD
Johns Hopkins University School of Medicine

Francesco Boin, MD
Cedars-Sinai Medical Center

In collaboration with:

Dan Kastner, MD, PhD
Charles Rotimi, PhD
National Human Genome Research Institute (NHGRI)

Pravitt Gourh, MD
National Institutes of Arthritis and Musculoskeletal Diseases (NIAMS)

The GRASP Consortium Institutions

Boston University • Cedars Sinai Medical Center • Columbia University • Emory University • Georgetown University • George Washington University• Henry Ford Health System • Hospital for Special Surgery • Johns Hopkins University • Medical University of South Carolina • New York University • NIH • Northwestern University  Rutgers University • Stanford University • Tulane University • University of Alabama–Birmingham • UCLA • UCSF • University of Chicago • University of Cincinnati • University of Michigan • University of Pennsylvania University of Pittsburgh • University of Rochester • University of Texas-Houston • Yale University

Background

Many epidemiological studies have suggested that ethnic differences exist in the susceptibility to and severity of scleroderma (systemic sclerosis). For example, it has been reported that African Americans have a higher age-specific incidence and prevalence of scleroderma compared to European Americans, an earlier age of onset, and more severe disease manifestations.

To date, attempts to elucidate the factors influencing increased disease incidence, prevalence, and severity have been hindered by the relatively small size of studied African American scleroderma cohorts.

Purpose

The GRASP Project was established to enhance our understanding of the clinical manifestations of scleroderma in African Americans and to perform genomic analyses with the aim of identifying key factors contributing to the onset and severity of their disease.

In order to achieve these goals, a large cohort of African American scleroderma patients is currently being enrolled. Clinical data as well as DNA samples have been collected from all enrolled patients.

Results and Progress

The GRASP cohort currently consists of more than 1,350 extensively evaluated African American scleroderma patients enrolled from 23 participating U.S. academic centers. This is the largest multicenter cohort of African American scleroderma patients ever studied. GRASP’s comprehensive clinical database (at Johns Hopkins) and its significant size are enabling important analyses. These have included a careful characterization of the relevant clinical features and the analysis of the specific repertoire of autoantibodies presented by African American patients.

The analysis of the GRASP cohort from a clinical perspective has confirmed the unique and severe disease burden of scleroderma in African Americans and highlights key factors associated with clinically relevant disease outcomes.

For example, the incidence of severe scleroderma-associated interstitial lung disease (SSc-ILD) and pulmonary arterial hypertension (PAH) was confirmed to be higher in this ethnic group compared to others. Socioeconomic factors and impaired access to health care do not fully account for the predilection of African American scleroderma patients to poor clinical outcomes. (See Morgan, et. al. Medicine, 2017.)

The GRASP consortium is now working to define how genomic variation of African American patients may affect the expression of scleroderma through DNA sequencing and other studies at the NHGRI and NIAMS. Subtle and rare genomic differences between African Americans who have scleroderma and unaffected African Americans or other ethnic populations may explain their increased risk of developing scleroderma as well as the particular array of severe clinical manifestations.

Consistent with the underlying assumptions of the project, GRASP investigators have found unique African ancestry-derived genetic variants increase the risk of scleroderma and various SSc-related complications in the studied African American population. (See Gourh, et. al., Arthritis Rheumatol., 2017; Gourh, et. al., PNAS, 2020.)

The GRASP Project will broaden our understanding of scleroderma and enable more effective care to African Americans affected by this condition. GRASP investigators are confident that the discoveries prompted by GRASP will have a major impact also for patients of other ethnic backgrounds as genomic variants critical for the development of scleroderma and its specific disease manifestations could be shared across different ethnicities or subsets of patients with worse disease outcomes. This will help to decipher the fundamental biological processes that cause scleroderma to occur and progress with greater precision.

Patient Enrollment

For information on enrolling patients in this landmark project, please contact us at GRASP@srfcure.org

Financial support for the GRASP Project is provided by the National Human Genome Research Insititute (NHGRI) and the Scleroderma Research Foundation (SRF), America’s largest nonprofit investor in scleroderma research.