Linkage and association studies of joint morbidity from rheumatoid arthritis.
OBJECTIVE
To investigate the relationship between genetic variations of rheumatoid arthritis (RA) susceptibility in terms of joint morbidity.


METHODS
We used data from Genetic Analysis Workshop 15. The Illumina linkage panel IV included 5858 single-nucleotide polymorphisms (SNP), with 5744 SNP passing quality control filters. The phenotypic variables analyzed were the level of rheumatoid factor (RF) and score on the Joint Alignment and Motion (JAM) scale. We modified the scale, dividing by RF values relevant to disease severity. Linkage analysis for affected sibling pairs was done using the MERLIN program, and family-based association tests were carried out using PLINK and FBAT software.


RESULTS
We found a high peak (LOD = 3.29; NPL Z = 4.07) near the HLA-DRB1 region on chromosome 6. The linkage at 6p24 at rs1410766 [LOD = 2.66; nonparametric linkage (NPL) Z = 3.23] was statistically significant. Two other regions also showed possible linkage peaks: chromosome 7q30 at rs322812 (LOD = 2.47; NPL Z = 3.39) and chromosome 15p34 at rs347117 (LOD = 1.95; NPL Z = 2.80). For the family-based association study, 7 SNP related to clinical RA severity were detected.


CONCLUSIONS
Genetic variations may lead to an enhanced risk of joint damage and increased levels of RF. Further studies are needed to elucidate the roles of other genes involved in RA and to explore whether the clinical signs of RA are associated with particular genetic variations.
Min
Jin-Young
JY
Institute of Health and Environment, Department of Epidemiology, School of Public Health, Seoul National University, Seoul, South Korea.
Min
Kyoung-Bok
KB
Sung
Joohon
J
Cho
Sung-Il
SI
D000328:Adult; D017668:Age of Onset; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000276:immunology; D002874:Chromosome Mapping; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007596:Joints / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012217:Rheumatoid Factor / Q000276:immunology; D012720:Severity of Illness Index; D035781:Siblings
D012217:Rheumatoid Factor