ArticleArthritis & rheumatology (Hoboken, N.J.)2016
Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 7 of them syntheses that pooled it.
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Who cites it
92 citing papers in PubMed, 7 syntheses or guidelines pooled it, 163 citations in OpenAlex.
- Possible linking and treatment between Parkinson's disease and inflammatory bowel disease: a study of Mendelian randomization based on gut-brain axis.Journal of translational medicine · 2025Pooled it
- Multi-ancestry and multi-trait genome-wide association meta-analyses inform clinical risk prediction for systemic lupus erythematosus.Nature communications · 2023Pooled it
- Mer-tyrosine kinase: a novel susceptibility gene for SLE related end-stage renal disease.Lupus science & medicine · 2022Pooled it
- TNFSF4 is a risk factor to systemic lupus erythematosus in a Latin American population.Clinical rheumatology · 2021Pooled it
- First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL,Annals of the rheumatic diseases · 2018Guideline
- Association between STAT4 polymorphisms and risk of primary biliary cholangitis: a meta-analysis.Genes & genomics · 2018Pooled it
- Cross-phenotype analysis of Immunochip data identifiesAnnals of the rheumatic diseases · 2018Pooled it
- Rare variants in non-coding regulatory regions of the genome that affect gene expression in systemic lupus erythematosus.Scientific reports · 2019Trial
- A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus.Human molecular genetics · 2018Trial
- Trial
- Baseline characteristics of patients with SLE with and without lupus nephritis from the Latin American multiethnic GLADEL 2.0 cohort.Lupus science & medicine · 2026Observational
- HLA - C*03:02:02 and DPA1*01:03:01 protect against discoid rash in Thai Systemic Lupus Erythematosus patients.Scientific reports · 2026Article
- Variants inInternational journal of molecular sciences · 2026Article
- Novel variants in ARID1B, SPSB1, and RAET1-AS shape genetic susceptibility and protection in systemic lupus erythematosus and lupus nephritis.Journal of translational autoimmunity · 2025Article
- Recent insights into the role of innate immunity in lupus.Human molecular genetics · 2025Review
- Item-specific factors associated with damage accrual in systemic lupus erythematosus: insights from a multiethnic, multinational Latin American cohort.Lupus science & medicine · 2025Article
- Review
- Long-read sequencing reveals novel isoform-specific eQTLs and regulatory mechanisms of isoform expression in human B cells.Genome biology · 2025Article
- An overview on Sjögren's syndrome and systemic lupus erythematosus' genetics.Toxicology research · 2025Review
- Breaking research silos to achieve equitable precision medicine in rheumatology.Nature reviews. Rheumatology · 2025Review
32 more citing papers are in PubMed but not listed here.
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Authors and funding
45 authors at 20 institutions in 7 countries.
Funding
Abstract
objectiveSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with a strong genetic component. We undertook the present work to perform the first genome-wide association study on individuals from the Americas who are enriched for Native American heritage.
methodsWe analyzed 3,710 individuals from the US and 4 countries of Latin America who were diagnosed as having SLE, and healthy controls. Samples were genotyped with HumanOmni1 BeadChip. Data on out-of-study controls genotyped with HumanOmni2.5 were also included. Statistical analyses were performed using SNPtest and SNPGWA. Data were adjusted for genomic control and false discovery rate. Imputation was performed using Impute2 and, for classic HLA alleles, HiBag. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.
resultsThe IRF5-TNPO3 region showed the strongest association and largest OR for SLE (rs10488631: genomic control-adjusted P [Pgcadj ] = 2.61 × 10(-29), OR 2.12 [95% CI 1.88-2.39]), followed by HLA class II on the DQA2-DQB1 loci (rs9275572: Pgcadj = 1.11 × 10(-16), OR 1.62 [95% CI 1.46-1.80] and rs9271366: Pgcadj = 6.46 × 10(-12), OR 2.06 [95% CI 1.71-2.50]). Other known SLE loci found to be associated in this population were ITGAM, STAT4, TNIP1, NCF2, and IRAK1. We identified a novel locus on 10q24.33 (rs4917385: Pgcadj = 1.39 × 10(-8)) with an expression quantitative trait locus (eQTL) effect (Peqtl = 8.0 × 10(-37) at USMG5/miR1307), and several new suggestive loci. SLE risk loci previously identified in Europeans and Asians were corroborated. Local ancestry estimation showed that the HLA allele risk contribution is of European ancestral origin. Imputation of HLA alleles suggested that autochthonous Native American haplotypes provide protection against development of SLE.
conclusionOur results demonstrate that studying admixed populations provides new insights in the delineation of the genetic architecture that underlies autoimmune and complex diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.