Dataset Information

Insecticide use and risk of rheumatoid arthritis and systemic lupus erythematosus in the Women's Health Initiative Observational Study.

ABSTRACT: OBJECTIVE:Farming and agricultural pesticide use has been associated with 2 autoimmune rheumatic diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, risk associated with other residential or work place insecticide use is unknown. METHODS:We analyzed data from the Women's Health Initiative Observational Study (n=76,861 postmenopausal women, ages 50-79 years). Incident cases (n=213: 178 for RA, 27 for SLE, and 8 for both) were identified based on self-report and use of disease-modifying antirheumatic drugs at year 3 of followup. We examined self-reported residential or work place insecticide use (personally mixing/applying by self and application by others) in relation to RA/SLE risk, overall and in relation to farm history. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were adjusted for age, race, region, education, occupation, smoking, reproductive factors, asthma, other autoimmune diseases, and comorbidities. RESULTS:Compared with never used, personal use of insecticides was associated with increased RA/SLE risk, with significant trends for greater frequency (HR 2.04, 95% CI 1.17-3.56 for ?6 times/year) and duration (HR 1.97, 95% CI 1.20-3.23 for ?20 years). Risk was also associated with long-term insecticide application by others (HR 1.85, 95% CI 1.07-3.20 for ?20 years) and frequent application by others among women with a farm history (HR 2.73, 95% CI 1.10-6.78 for ?6 times/year). CONCLUSION:These results suggest residential and work place insecticide exposure is associated with the risk of autoimmune rheumatic diseases in postmenopausal women. Although these findings require replication in other populations, they support a role for environmental pesticide exposure in the development of autoimmune rheumatic diseases.

SUBMITTER: Parks CG

PROVIDER: S-EPMC3593584 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Insecticide use and risk of rheumatoid arthritis and systemic lupus erythematosus in the Women's Health Initiative Observational Study.

Parks Christine G CG Walitt Brian T BT Pettinger Mary M Chen Jiu-Chiuan JC de Roos Anneclaire J AJ Hunt Julie J Sarto Gloria G Howard Barbara V BV

Arthritis care & research 20110201 2

<h4>Objective</h4>Farming and agricultural pesticide use has been associated with 2 autoimmune rheumatic diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, risk associated with other residential or work place insecticide use is unknown.<h4>Methods</h4>We analyzed data from the Women's Health Initiative Observational Study (n=76,861 postmenopausal women, ages 50-79 years). Incident cases (n=213: 178 for RA, 27 for SLE, and 8 for both) were identified based on sel ...[more]

PMID: 20740609

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Project description:BackgroundRheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q.MethodsWe tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. We then performed fine mapping of the STAT1-STAT4 region in a total of 1620 case patients with established rheumatoid arthritis and 2635 controls, all from North America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus.ResultsA SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P=2.81x10(-7); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P=0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P=1.87x10(-9); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis.ConclusionsA haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses.

Project description:BackgroundClinical and epidemiological studies have suggested systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are comorbidities and common genetic etiologies can partly explain such coexistence. However, shared genetic determinations underlying the two diseases remain largely unknown.MethodsOur analysis relied on summary statistics available from genome-wide association studies of SLE (N = 23,210) and RA (N = 58,284). We first evaluated the genetic correlation between RA and SLE through the linkage disequilibrium score regression (LDSC). Then, we performed a multiple-tissue eQTL (expression quantitative trait loci) weighted integrative analysis for each of the two diseases and aggregated association evidence across these tissues via the recently proposed harmonic mean P-value (HMP) combination strategy, which can produce a single well-calibrated P-value for correlated test statistics. Afterwards, we conducted the pleiotropy-informed association using conjunction conditional FDR (ccFDR) to identify potential pleiotropic genes associated with both RA and SLE.ResultsWe found there existed a significant positive genetic correlation (r g = 0.404, P = 6.01E-10) via LDSC between RA and SLE. Based on the multiple-tissue eQTL weighted integrative analysis and the HMP combination across various tissues, we discovered 14 potential pleiotropic genes by ccFDR, among which four were likely newly novel genes (i.e., INPP5B, OR5K2, RP11-2C24.5, and CTD-3105H18.4). The SNP effect sizes of these pleiotropic genes were typically positively dependent, with an average correlation of 0.579. Functionally, these genes were implicated in multiple auto-immune relevant pathways such as inositol phosphate metabolic process, membrane and glucagon signaling pathway.ConclusionThis study reveals common genetic components between RA and SLE and provides candidate associated loci for understanding of molecular mechanism underlying the comorbidity of the two diseases.

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Insecticide use and risk of rheumatoid arthritis and systemic lupus erythematosus in the Women's Health Initiative Observational Study.

Publications

Insecticide use and risk of rheumatoid arthritis and systemic lupus erythematosus in the Women's Health Initiative Observational Study.

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