ArticleArthritis research & therapy2014
Targeted exon sequencing fails to identify rare coding variants with large effect in rheumatoid arthritis.
Article in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Low-frequency and rare genetic variants associated with rheumatoid arthritis risk.Nature reviews. Rheumatology · 2024Review
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- Genome-wide identification of RNA modification-related single nucleotide polymorphisms associated with rheumatoid arthritis.BMC genomics · 2023Article
- Systemic lupus erythematosus as a genetic disease.Clinical immunology (Orlando, Fla.) · 2022Article
- Missense variant in interleukin-6 signal transducer identified as susceptibility locus for rheumatoid arthritis in Chinese patients.Archives of rheumatology · 2021Article
- Latin American Genes: The Great Forgotten in Rheumatoid Arthritis.Journal of personalized medicine · 2020Review
- Targeted next generation sequencing of nine osteoporosis-related genes in the Wnt signaling pathway among Chinese postmenopausal women.Endocrine · 2020Article
- The Potential Role of Genomic Medicine in the Therapeutic Management of Rheumatoid Arthritis.Journal of clinical medicine · 2019Review
- Article
- Genome-Wide SNP Discovery in Indigenous Cattle Breeds of South Africa.Frontiers in genetics · 2019Article
- Exploiting the great potential of Sequence Capture data by a new tool, SUPER-CAP.DNA research : an international journal for rapid publication of reports on genes and genomes · 2017Article
- Update on the genetic architecture of rheumatoid arthritis.Nature reviews. Rheumatology · 2017Review
- Recent Advances in Defining the Genetic Basis of Rheumatoid Arthritis.Annual review of genomics and human genetics · 2016Review
- Rare variants, autoimmune disease, and arthritis.Current opinion in rheumatology · 2016Review
- Autoimmune diseases - connecting risk alleles with molecular traits of the immune system.Nature reviews. Genetics · 2016Review
- Article
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Authors and funding
16 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionAlthough it has been suggested that rare coding variants could explain the substantial missing heritability, very few sequencing studies have been performed in rheumatoid arthritis (RA). We aimed to identify novel functional variants with rare to low frequency using targeted exon sequencing of RA in Korea.
methodsWe analyzed targeted exon sequencing data of 398 genes selected from a multifaceted approach in Korean RA patients (n = 1,217) and controls (n = 717). We conducted a single-marker association test and a gene-based analysis of rare variants. For meta-analysis or enrichment tests, we also used ethnically matched independent samples of Korean genome-wide association studies (GWAS) (n = 4,799) or immunochip data (n = 4,722).
resultsAfter stringent quality control, we analyzed 10,588 variants of 398 genes from 1,934 Korean RA case controls. We identified 13 nonsynonymous variants with nominal association in single-variant association tests. In a meta-analysis, we did not find any novel variant with genome-wide significance for RA risk. Using a gene-based approach, we identified 17 genes with nominal burden signals. Among them, VSTM1 showed the greatest association with RA (P = 7.80 × 10-4). In the enrichment test using Korean GWAS, although the significant signal appeared to be driven by total genic variants, we found no evidence for enriched association of coding variants only with RA.
conclusionsWe were unable to identify rare coding variants with large effect to explain the missing heritability for RA in the current targeted resequencing study. Our study raises skepticism about exon sequencing of targeted genes for complex diseases like RA.
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