Exploring potential shared genetic influences between rheumatoid arthritis and blood lipid levels

Kasher, Melody; Cherny, Stacey S.; Livshits, Gregory

doi:10.1016/j.atherosclerosis.2022.11.006

Cited by 8 publications

(9 citation statements)

References 49 publications

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“…A Mendelian randomization study produced findings similar to those of the large population-based study. Kasher et al [ 33 ] performed a Mendelian randomization analysis revealed complex and contradictory relationships between lipid factors and RA. Importantly, their analysis did not suggest a causal link between RA and alterations in lipid factors.…”

Section: Discussionmentioning

confidence: 99%

The association between remnant cholesterol and rheumatoid arthritis: insights from a large population study

Yan,

La,

Jiang

et al. 2024

Lipids Health Dis

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Objectives While lipid metabolism disorder is widely acknowledged as a contributing factor to inflammation, the association between remnant cholesterol (RC), which indicates lipid metabolism, and rheumatoid arthritis (RA) has not been investigated. Accordingly, this study evaluated whether RC is associated with RA disease events. Methods Data were collected and specifically extracted from the National Health and Nutrition Examination Survey (NHANES) 1999–2008 database. The RC value was derived by subtracting the combined amount of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) from the total cholesterol (TC). The association between RC and RA was evaluated using multivariate regression analysis and subgroup analysis. Results The study analyzed 7777 patients, of which 581 patients (7.47%) were diagnosed with RA. After accounting for different covariates, the multivariate logistic regression analysis revealed a notable correlation between increased RC levels and an increased likelihood of RA (odds ratio OR = 1.54; 95% confidence interval CI: 1.11–2.13; P = 0.0092). The interaction test did not yield statistically significant effects on this association. The linear correlation between RC and RA was observed within restricted cubic spline regression model limitations. Conclusion The results suggest that higher RC levels are associated with increased odds of RA, indicating that RC can serve as a novel and convenient index for forecasting the likelihood of RA in the United States. Additionally, these findings offer insights into early intervention strategies for susceptible populations at risk of developing RA.

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Section: Discussionmentioning

confidence: 99%

The association between remnant cholesterol and rheumatoid arthritis: insights from a large population study

Yan,

La,

Jiang

et al. 2024

Lipids Health Dis

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“…For example, Kasher et al identified shared causal genetic variants for RA, in genes including PLCL1 , BOLL , NAT2 / PSD , 3 and FADS2 / FADS1 , by conducting colocalization analyses between RA and multiple RA related traits or diseases. 43 , 44 Another GWAS study described an association between carotid intima‐media thickness and a genetic marker of the RARB gene (lead SNP: rs116199914 ) at the genome‐wide level of significance in a European series of patients with RA. 45 Interestingly, rs116199914 has been described to interact with the NKIRAS1 gene.…”

Section: Discussionmentioning

confidence: 99%

Genome‐Wide Assessment of Shared Genetic Architecture Between Rheumatoid Arthritis and Cardiovascular Diseases

Guo,

Chung,

Shan

et al. 2023

JAHA

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Background Patients with rheumatoid arthritis (RA) have a 2‐ to 10‐fold increased risk of cardiovascular disease (CVD), but the biological mechanisms and existence of causality underlying such associations remain to be investigated. We aimed to investigate the genetic associations and underlying mechanisms between RA and CVD by leveraging large‐scale genomic data and genetic cross‐trait analytic approaches. Methods and Results Within UK Biobank data, we examined the genetic correlation, shared genetics, and potential causality between RA (N cases =6754, N controls =452 384) and cardiovascular diseases (CVD, N cases =44 238, N controls =414 900) using linkage disequilibrium score regression, cross‐trait meta‐analysis, and Mendelian randomization. We observed significant genetic correlations of RA with myocardial infarction (r g :0.40 [95% CI, 0.24–0.56), angina (r g :0.42 [95% CI, 0.28–0.56]), coronary heart diseases (r g :0.41 [95% CI, 0.27–0.55]), and CVD (r g :0.43 [95% CI, 0.29–0.57]) after correcting for multiple testing ( P <0.05/5). When stratified by frequent use of analgesics, we found increased genetic correlation between RA and CVD among participants without aspirin usage (r g :0.54 [95% CI, 0.30–0.78] for angina; P value =6.69×10 −6 ) and among participants with paracetamol usage (r g :0.75 [95% CI, 0.20–1.29] for myocardial infarction; P value =8.90×10 −3 ), whereas others remained similar. Cross‐trait meta‐analysis identified 9 independent shared loci between RA and CVD, including PTPN22 at chr1p13.2 , BCL2L11 at chr2q13 , and CCR3 at chr3p21.31 ( P single trait <1×10 −3 and P meta <5×10 −8 ), highlighting potential shared pathogenesis including accelerating atherosclerosis, upregulating oxidative stress, and vascular permeability. Finally, Mendelian randomization estimates showed limited evidence of causality between RA and CVD. Conclusions Our results supported shared genetic pathogenesis rather than causality in explaining the observed association between RA and CVD. The identified shared genetic factors provided insights into potential novel therapeutic target for RA‐CVD comorbidities.

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“…The present study was carried out in two stages: (1) assessing GlycA’s relationship with RA, atherosclerotic phenotypes, and lipid factors and (2) analyzing the relationship between RA and atherosclerotic phenotypes, excluding lipid factors. The underlying genetic architecture between RA and lipid factors was previously examined by us and reported elsewhere [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Glycoprotein Acetyls Is a Novel Biomarker Predicting Cardiovascular Complications in Rheumatoid Arthritis

Kasher,

Freidin,

Williams

et al. 2024

IJMS

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The relationship between rheumatoid arthritis (RA) and early onset atherosclerosis is well depicted, each with an important inflammatory component. Glycoprotein acetyls (GlycA), a novel biomarker of inflammation, may play a role in the manifestation of these two inflammatory conditions. The present study examined a potential mediating role of GlycA within the RA–atherosclerosis relationship to determine whether it accounts for the excess risk of cardiovascular disease over that posed by lipid risk factors. The UK Biobank dataset was acquired to establish associations among RA, atherosclerosis, GlycA, and major lipid factors: total cholesterol (TC), high- and low-density lipoprotein (HDL, LDL) cholesterol, and triglycerides (TGs). Genome-wide association study summary statistics were collected from various resources to perform genetic analyses. Causality among variables was tested using Mendelian Randomization (MR) analysis. Genes of interest were identified using colocalization analysis and gene enrichment analysis. MR results appeared to indicate that the genetic relationship between GlycA and RA and also between RA and atherosclerosis was explained by horizontal pleiotropy (p-value = 0.001 and <0.001, respectively), while GlycA may causally predict atherosclerosis (p-value = 0.017). Colocalization analysis revealed several functionally relevant genes shared between GlycA and all the variables assessed. Two loci were apparent in all relationships tested and included the HLA region as well as SLC22A1. GlycA appears to mediate the RA–atherosclerosis relationship through several possible pathways. GlycA, although pleiotropically related to RA, appears to causally predict atherosclerosis. Thus, GlycA is suggested as a significant factor in the etiology of atherosclerosis development in RA.

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Exploring potential shared genetic influences between rheumatoid arthritis and blood lipid levels

Cited by 8 publications

References 49 publications

The association between remnant cholesterol and rheumatoid arthritis: insights from a large population study

The association between remnant cholesterol and rheumatoid arthritis: insights from a large population study

Genome‐Wide Assessment of Shared Genetic Architecture Between Rheumatoid Arthritis and Cardiovascular Diseases

Glycoprotein Acetyls Is a Novel Biomarker Predicting Cardiovascular Complications in Rheumatoid Arthritis

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