RESEARCH - Linkage and association studies of joint morbidity from RA

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J Rheumatol. 2009 Dec 23.

Linkage and Association Studies of Joint Morbidity from Rheumatoid Arthritis.

Min JY, Min KB, Sung J, Il Cho S.

From the Institute of Health and Environment and the Department of

Epidemiology, School of Public Health, Seoul National University,

Seoul; and Department of Preventive Medicine, Ajou University School

of Medicine, Suwon, South Korea.

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.

CONCLUSION: 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.

PMID: 20032104

http://www.ncbi.nlm.nih.gov/pubmed/20032104

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