Genetic Architecture of Rheumatoid Arthritis in African-Americans

University Of Alabama At Birmingham, Birmingham AL

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Abstract

DESCRIPTION (provided by applicant): The applicant's career goal is to become an independently funded investigator in the genetics of rheumatic diseases, particularly rheumatoid arthritis (RA). To meet this goal, the applicant proposes a career development plan with emphasis on didactic training in the principles of epidemiology and statistical genetics methods by pursing courses towards a Masters of Science in Public Health in Clinical Research. In addition, she will obtain hands-on training in bioinformatics. She will become well versed in using state-of-the-art statistical techniques that can accommodate the unique challenges posed by large genetic data sets. The candidate has assembled a strong interdisciplinary mentoring team with proven track record of successful mentorship and academic accomplishment in rheumatology, epidemiology and statistical genetics. The research component of this mentored patient-oriented research career development award proposes to identify genetic associations with risk and severity of RA in African Americans and to build predictive models for RA risk and outcome using clinical and genomic data. Data from ~ 1000 African Americans RA participants and ~1700 African American controls is available from the NIH-funded Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR) Registry and from local and national collaborations. Genotyping data will be available from the ImmunoChip, a custom array of ~200,000 rare and common single nucleotide polymorphisms (SNPs) developed by the ImmunoChip Consortium. The ImmunoChip contains SNPs selected from the most strongly associated makers discovered in Caucasian and Asian populations through GWAS strategy in autoimmune diseases including RA, type 1 diabetes, lupus, celiac disease, autoimmune thyroid disease, inflammatory bowel disease, ankylosing spondylitis, psoriasis and other diseases. Genotyping is currently underway (see letter from Dr. Peter Gregersen) using institutional funds from UAB provided by Dr. Lou Bridges and will be available by the requested start date of this K23 application. The scientific aims of the study are: 1) to determine whether genetic markers of autoimmunity validated in European and Asian populations influence the risk of developing RA in African Americans; 2) to determine whether the genetic markers of susceptibility to RA play a role in radiographic severity of RA in African Americans; 3) to develop and test predictive models for RA risk and outcome using clinical and genetic data in African Americans. This project will greatly improve our understanding of the genetic influences on the RA risk and outcome and will provide essential training for Dr. Danila' development as an independent investigator.