Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis

Rector Arya, Inmaculada del Rincon, Vidya S. Farook, Jose F. Restrepo, Diedre A. Winnier, Marcel J. Fourcaudot, Daniel F. Battafarano, Marcio de Almeida, Satish Kumar, Joanne E. Curran, Christopher P. Jenkinson, John Blangero, Ravindranath Duggirala, Agustin Escalante

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Joint destruction in rheumatoid arthritis (RA) is heritable, but knowledge on specific genetic determinants of joint damage in RA is limited. We have used the Immunochip array to examine whether genetic variants influence variation in joint damage in a cohort of Mexican Americans (MA) and European Americans (EA) with RA. We studied 720 MA and 424 EA patients with RA. Joint damage was quantified using a radiograph of both hands and wrists, scored using Sharp's technique. We conducted association analyses with the transformed Sharp score and the Immunochip single nucleotide polymorphism (SNP) data using PLINK. In MAs, 15 SNPs from chromosomes 1, 5, 9, 17 and 22 associated with joint damage yielded strong p-values (p <1 × 10-4). The strongest association with joint damage was observed with rs7216796, an intronic SNP located in the MAP3K14 gene, on chromosome 17 (β ± SE = -0.25 ± 0.05, p = 6.23 × 10-6). In EAs, 28 SNPs from chromosomes 1, 4, 6, 9, and 21 showed associations with joint damage (p-value <1 × 10-4). The best association was observed on chromosome 9 with rs59902911 (β ± SE = 0.86 ± 0.17, p = 1.01 × 10-6), a synonymous SNP within the CARD9 gene. We also observed suggestive evidence for some loci influencing joint damage in MAs and EAs. We identified two novel independent loci (MAP3K14 and CARD9) strongly associated with joint damage in MAs and EAs and a few shared loci showing suggestive evidence for association.

Original languageEnglish (US)
Pages (from-to)678-688
Number of pages11
JournalGenetic Epidemiology
Volume39
Issue number8
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

Keywords

  • European Americans
  • Genetic association
  • Joint damage
  • Mexican Americans
  • Rheumatoid arthritis susceptibility loci

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

Fingerprint Dive into the research topics of 'Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis'. Together they form a unique fingerprint.

  • Cite this

    Arya, R., del Rincon, I., Farook, V. S., Restrepo, J. F., Winnier, D. A., Fourcaudot, M. J., Battafarano, D. F., de Almeida, M., Kumar, S., Curran, J. E., Jenkinson, C. P., Blangero, J., Duggirala, R., & Escalante, A. (2015). Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis. Genetic Epidemiology, 39(8), 678-688. https://doi.org/10.1002/gepi.21938