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Unraveling the genetics of scleroderma in African-Americans

Friday, September 18, 2015 — Poster Session IV

12:00 p.m. – 1:30 p.m.
FAES Terrace


  • P Gourh
  • F Boin
  • E Remmers
  • J Mullikin
  • C Derk
  • R Domsic
  • H Gladue
  • H Gladue
  • J Gordon
  • M Mayes
  • L Saketkoo
  • E Schiopu
  • V Shanmugam
  • R Silver
  • V Steen
  • M Trojanowski
  • J Varga
  • C Rotimi
  • F Wigley
  • D Kastner


Background: African-Americans(AA) develop systemic sclerosis(SSc;scleroderma) at an earlier age, have a higher prevalence, a more severe phenotype and an increased risk for mortality as compared to European-Americans(EA). Majority of the AA derive their ancestry from Western Africa and Africans have a SSc phenotype that is very similar to AA and different from EA. We hypothesize that the higher prevalence and severe phenotype of SSc in AA is due to the genetic variants derived from their African ancestry. We are utilizing this fact and adopting a comprehensive approach of testing common and low-frequency/rare-variants and applying admixture mapping to identify SSc associated loci. Materials and methods: A multicenter consortium, GRASP(Genome Research in African-American Scleroderma Patients) across US is collecting samples. Controls will be tested for ANA by indirect-immunofluorescence(ANA-IIF). Whole exome sequencing(WES) to identify rare variants unique to SSc and genotyping for common variants using multiple arrays will be performed on the 1000 SSc and 1000 controls. Admixture mapping analysis and common/rare variant association analysis will be used to identify SSc susceptibility loci. Results: DNA from 875 AA SSc patients has been collected. 1039 (97.8%) out of 1062 control sera were found to be negative for ANA-IIF at 1:80 titer and 1000 ANA-negative controls have been selected. WES on 400 AA SSc patients and 400 controls has been completed. Rare/low-frequency variant analysis and array genotyping is ongoing. Conclusions: This is the first study of its kind and scope to comprehensively test common and low frequency/rare variants associated with SSc susceptibility in AA patients.

Category: Genetics and Genomics