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A principal-components-based clustering method to identify multiple variants associated with rheumatoid arthritis and arthritis-related autoantibodies.

ABSTRACT: Multivariate techniques are an important area of investigation for studying contributions of multiple genetic variants to disease onset and pathology. We analyzed the Genetic Analysis Workshop 16 North American Rheumatoid Arthritis Consortium (NARAC) data using a principal-components analysis (PCA) with an orthoblique rotation to identify specific subsets of single-nucleotide polymorphisms (SNP) in the major histocompatibility complex (MHC) region associated with rheumatoid arthritis (RA) and rheumatoid factor IgM (RFUW), and compared this method with a traditional PC approach. Using the orthoblique PC-based clustering method, we identified new clusters of SNPs across the MHC region associated with RA and RFUW, and replicated known SNP cluster associations with RA, such as those in the HLA-DRB region.

SUBMITTER: Black MH

PROVIDER: S-EPMC2795902 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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A principal-components-based clustering method to identify multiple variants associated with rheumatoid arthritis and arthritis-related autoantibodies.

Black Mary Helen MH Watanabe Richard M RM

BMC proceedings 20091215

Multivariate techniques are an important area of investigation for studying contributions of multiple genetic variants to disease onset and pathology. We analyzed the Genetic Analysis Workshop 16 North American Rheumatoid Arthritis Consortium (NARAC) data using a principal-components analysis (PCA) with an orthoblique rotation to identify specific subsets of single-nucleotide polymorphisms (SNP) in the major histocompatibility complex (MHC) region associated with rheumatoid arthritis (RA) and rh ...[more]

PMID: 20017995

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Project description:IntroductionWe investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with abnormalities on pulmonary function tests (PFTs).MethodsWe studied RA serostatus and PFT abnormalities within a RA registry. RA serostatus was assessed by research assays for cyclic citrullinated peptide (CCP) and rheumatoid factor (RF). Outcomes were abnormalities on clinically indicated PFTs, including restriction, obstruction, and diffusion abnormality. Logistic regression was used to obtain ORs and 95% CIs for the PFT abnormalities by RA serologic phenotypes independent of lifestyle and RA characteristics.ResultsAmong 1272 analyzed subjects, mean age was 56.3 years (SD 14.1), 82.2% were female, and 69.5% were seropositive. There were 100 subjects with abnormal PFTs. Compared with seronegativity, seropositivity was associated with increased odds of any PFT abnormality (multivariable OR 2.29, 95% CI 1.30-4.03). When analyzing type of PFT abnormality, seropositivity was also associated with restriction, obstruction, and diffusion abnormalities; multivariable ORs were 2.48 (95% CI 1.26-4.87), 3.12 (95% CI 1.28-7.61), and 2.30 (95% CI 1.09-4.83), respectively. When analyzing by CCP and RF status, the associations were stronger for RF+ than for CCP+ (any PFT abnormality OR 1.99, 95% CI 1.21-3.27 for RF+ vs. RF-; OR 1.67, 95% CI 1.03-2.69 for CCP+ vs. CCP-) with a dose effect of higher RF titer increasing odds for each PFT abnormality (p for trend < 0.05).ConclusionsSeropositive RA patients had two-fold increased risk for abnormalities on PFTs performed for clinical indications compared with seronegative RA. Patients with seropositive RA, particularly those with high-titer RF positivity, may be more likely to have obstructive and restrictive abnormalities, independent of smoking.Key points• Due to the known excess pulmonary morbidity/mortality in RA, we studied the relationship of rheumatoid arthritis (RA)-related autoantibodies with pulmonary function test (PFT) abnormalities using a large RA registry.• We evaluated whether presence and levels of cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were associated with restriction, obstruction, and diffusion abnormalities on PFTs among 1272 subjects with RA.• Seropositivity was associated with two-fold increased risk for any PFT abnormality, independent of confounders including smoking. Higher titers of RF conferred greatest risk for all PFT outcomes: obstruction, restriction, and diffusion abnormality.• These results provide evidence that patients with RA should be closely monitored for pulmonary involvement, particularly those with high-titer RF seropositivity.

Dataset Information

A principal-components-based clustering method to identify multiple variants associated with rheumatoid arthritis and arthritis-related autoantibodies.

Publications

A principal-components-based clustering method to identify multiple variants associated with rheumatoid arthritis and arthritis-related autoantibodies.

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