Genome-wide identification of RNA modification-related single nucleotide polymorphisms associated with rheumatoid arthritis

Wang, Mimi; Lei, Shu‐Feng; Mo, Xing‐Bo

doi:10.1186/s12864-023-09227-2

Cited by 11 publications

(4 citation statements)

References 63 publications

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“…In addition, considering that RNAm-SNPs can affect protein expression levels [38,39], 78 eGFR-RNAm-SNPs related to m 6 A, m 1 A, A-to-I, m 7 G or m 5 C showed pQTL signals in our study. We conducted the TSMR analysis between pQTL datasets as exposures and eGFR as the outcome.…”

Section: Discussionmentioning

confidence: 56%

WITHDRAWN: Multi-omics predicts risk factors for kidney disease associated with RNA modification

Liu,

Zhu,

Liu

et al. 2023

Preprint

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Background More and more evidence suggests that RNA modification play significant roles in kidney and may be ideal targets of kidney diseases. However, the specific mechanisms of RNA modification in the pathogenesis of kidney diseases remain unclear. Genome-wide association study (GWAS) have identified lots of genetic loci for kidney function and RNA modification. The identification and exploration of the functions of kidney function associated with RNAm-SNPs can help us to explore comprehensive understanding of the underlying mechanism of kidney disease and find potential therapeutic targets. Methods First, we examined the association of RNAm-SNPs with kidney function. Secondly, we performed eQTL and pQTL analyses to explore the function of these identified RNAm-SNPs. Finally, we evaluated the causality between RNAm-SNPs associated gene expression and circulating protein and kidney function by using mendelian randomization analysis and Bayesian colocalization test (coloc). Results 370 RNAm-SNPs related to m6A, m1A, A-to-I, m5C, m7G and m5U modifications were identified. All of them was significantly associated with kidney function. Most of these RNAm-SNPs (60.27%) showed cis-eQTL effects in kidney tissues or in blood cells, while 78 RNAm-SNPs (21.08%) showed cis-pQTL effects in plasma. In addition, we demonstrate a causal association of some RNAm-SNPs associated gene expression and circulating protein with the risk for kidney function. Notably, we demonstrate a causal association of the gene expression in blood and plasma protein of ITIH4 with the risk for kidney function. Conclusions The study found the associations between RNAm-SNPs and kidney function. These SNPs can regulate gene expression and protein levels by RNA modification, eventually leading to kidney dysfunction. Our study provided direct evidences that connect the genetic risk of kidney disease to RNA modification and the new idea for potential therapeutic targets of prevention and treatment of kidney disease.

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Section: Discussionmentioning

confidence: 56%

WITHDRAWN: Multi-omics predicts risk factors for kidney disease associated with RNA modification

Liu,

Zhu,

Liu

et al. 2023

Preprint

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“…[ 35 ] In several populations, genome-wide association research found more than 100 loci associated with RA risk. [ 36 ] The HLA gene region is a genetic risk factor for RA. Gene expression levels for HLA-A and HLA-B are associated with RA.…”

Section: Discussionmentioning

confidence: 99%

Causal association between rheumatoid arthritis and an increased risk of age-related macular degeneration: A Mendelian randomization study

Zhang,

Duan,

Feng

2024

Medicine

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This study’s goal is to evaluate if there is a causal connection between rheumatoid arthritis (RA) and age-related macular degeneration (AMD), despite past epidemiological studies suggesting an association between the 2 disorders. The impact of RA on AMD is still unknown. Mendelian randomization (MR) was utilized in this study to assess the two-sample causal relationship between RA and AMD. Summary data from GWAS for RA and AMD in individuals with all European ancestries were gathered using the IEU GWAS database. The GWAS summary statistics of RA (14,361 RA patients and 43,923 healthy controls) and AMD (14,034 AMD patients and 91,214 controls participated) were obtained from the IEU GWAS database. After identifying suitable instrumental variables in line with the 3 MR assumptions, we conducted MR using the Mendelian randomization-Egger (MR-Egger), weighted median, and inverse variance weighting techniques. The MR-Egger intercept and MR-Polyvalent Residuals and Outliers methods were used to investigate the effects of horizontal pleiotropy. The leave-one-out strategy was used to prevent bias caused by certain single nucleotide polymorphisms. Sensitivity analysis was used to detect the heterogeneity. Using 50 single nucleotide polymorphisms as instrumental variables, this study examined the relationship between RA and AMD and discovered that RA increased the risk of AMD (inverse variance weighting odds ratio [OR] = 1.056, 95% confidence interval [CI] = 1.02–1.09, P = 5.44E−04; weighted median OR = 1.085, 95% CI = 1.04–1.14, P = 4.05E−04; MR-Egger OR = 1.074, 95% CI = 1.01–1.14, P = 2.18E−2). The current investigation demonstrated a causal link between AMD and RA. RA increased the risk of AMD. It is advised that future research concentrate on the processes underlying the relationship between RA and AMD.

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“…The association of DRB1 *04 and genetic predisposition for rheumatoid arthritis (RA) has been observed since the late 1980s ( 76 , 77 ). RA is the autoimmune destruction of the synovium in the small joints characterized by the presence of autoantibodies: rheumatoid factor, anti-cyclic citrullinated peptide-2, and anti-carbamylated protein ( 78 , 79 ). Within the Caucasian population of RA patients, significant associations are seen with DRB1 *04:01, DRB1 *04:04, DRB1 *04:05 and 95% of those with severe arthritis expressed DRB1 *04:01 ( 80 , 81 ).…”

Section: Class II Hla Autoimmunity Associationmentioning

confidence: 99%

Important denominator between autoimmune comorbidities: a review of class II HLA, autoimmune disease, and the gut

Berryman,

Ilonen,

Triplett

et al. 2023

Front. Immunol.

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Human leukocyte antigen (HLA) genes are associated with more diseases than any other region of the genome. Highly polymorphic HLA genes produce variable haplotypes that are specifically correlated with pathogenically different autoimmunities. Despite differing etiologies, however, many autoimmune disorders share the same risk-associated HLA haplotypes often resulting in comorbidity. This shared risk remains an unanswered question in the field. Yet, several groups have revealed links between gut microbial community composition and autoimmune diseases. Autoimmunity is frequently associated with dysbiosis, resulting in loss of barrier function and permeability of tight junctions, which increases HLA class II expression levels and thus further influences the composition of the gut microbiome. However, autoimmune-risk-associated HLA haplotypes are connected to gut dysbiosis long before autoimmunity even begins. This review evaluates current research on the HLA-microbiome-autoimmunity triplex and proposes that pre-autoimmune bacterial dysbiosis in the gut is an important determinant between autoimmune comorbidities with systemic inflammation as a common denominator.

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Genome-wide identification of RNA modification-related single nucleotide polymorphisms associated with rheumatoid arthritis

Cited by 11 publications

References 63 publications

WITHDRAWN: Multi-omics predicts risk factors for kidney disease associated with RNA modification

WITHDRAWN: Multi-omics predicts risk factors for kidney disease associated with RNA modification

Causal association between rheumatoid arthritis and an increased risk of age-related macular degeneration: A Mendelian randomization study

Important denominator between autoimmune comorbidities: a review of class II HLA, autoimmune disease, and the gut

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