TY - JOUR
T1 - Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis
AU - Arya, Rector
AU - del Rincon, Inmaculada
AU - Farook, Vidya S.
AU - Restrepo, Jose F.
AU - Winnier, Deidre A
AU - Fourcaudot, Marcel J.
AU - Battafarano, Daniel F.
AU - de Almeida, Marcio
AU - Kumar, Satish
AU - Curran, Joanne E
AU - Jenkinson, Christopher P
AU - Blangero, John C
AU - Duggirala, Ravindranath
AU - Escalante, Agustin
N1 - Publisher Copyright:
© 2015 Wiley Periodicals, Inc.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - European Americans
KW - Genetic association
KW - Joint damage
KW - Mexican Americans
KW - Rheumatoid arthritis susceptibility loci
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U2 - 10.1002/gepi.21938
DO - 10.1002/gepi.21938
M3 - Article
C2 - 26498133
AN - SCOPUS:84954385868
SN - 0741-0395
VL - 39
SP - 678
EP - 688
JO - Genetic epidemiology
JF - Genetic epidemiology
IS - 8
ER -