scholarly journals Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as Susceptibility Loci for Systemic Lupus Erythematosus in a Large-Scale Multiracial Replication Study

2012 ◽  
Vol 90 (4) ◽  
pp. 648-660 ◽  
Author(s):  
Christopher J. Lessard ◽  
Indra Adrianto ◽  
John A. Ice ◽  
Graham B. Wiley ◽  
Jennifer A. Kelly ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Large Scale ◽  
Replication Study ◽  
Susceptibility Loci ◽  
Systemic Lupus

scholarly journals Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus

2020 ◽  
pp. annrheumdis-2020-219209
Author(s):  
Xianyong Yin ◽  
Kwangwoo Kim ◽  
Hiroyuki Suetsugu ◽  
So-Young Bang ◽  
Leilei Wen ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Large Scale ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Susceptibility Loci ◽  
Systemic Lupus ◽  
East Asians ◽  
Genome Wide ◽  
Causal Variants

ObjectiveSystemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.MethodsWe newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations.ResultsWe identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10−8). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (rg=−0.242) and non-albumin protein (rg=0.238).ConclusionThis study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.

scholarly journals Update on the Genetics of Systemic Lupus Erythematosus: Genome-Wide Association Studies and Beyond

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1180 ◽  
Author(s):  
Kwon ◽  
Chun ◽  
Kim ◽  
Mak
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Large Scale ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Childbearing Age ◽  
Systemic Lupus ◽  
Risk Variants ◽  
The Impact

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of complex etiology that primarily affects women of childbearing age. The development of SLE is attributed to the breach of immunological tolerance and the interaction between SLE-susceptibility genes and various environmental factors, resulting in the production of pathogenic autoantibodies. Working in concert with the innate and adaptive arms of the immune system, lupus-related autoantibodies mediate immune-complex deposition in various tissues and organs, leading to acute and chronic inflammation and consequent end-organ damage. Over the past two decades or so, the impact of genetic susceptibility on the development of SLE has been well demonstrated in a number of large-scale genetic association studies which have uncovered a large fraction of genetic heritability of SLE by recognizing about a hundred SLE-susceptibility loci. Integration of genetic variant data with various omics data such as transcriptomic and epigenomic data potentially provides a unique opportunity to further understand the roles of SLE risk variants in regulating the molecular phenotypes by various disease-relevant cell types and in shaping the immune systems with high inter-individual variances in disease susceptibility. In this review, the catalogue of SLE susceptibility loci will be updated, and biological signatures implicated by the SLE-risk variants will be critically discussed. It is optimistically hoped that identification of SLE risk variants will enable the prognostic and therapeutic biomarker armamentarium of SLE to be strengthened, a major leap towards precision medicine in the management of the condition.

scholarly journals A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus

2009 ◽  
Vol 41 (11) ◽  
pp. 1228-1233 ◽  
Author(s):  
Vesela Gateva ◽  
Johanna K Sandling ◽  
Geoff Hom ◽  
Kimberly E Taylor ◽  
Sharon A Chung ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Large Scale ◽  
Replication Study ◽  
Systemic Lupus

scholarly journals Brief Report: Large-scale analysis of tumor necrosis factor α levels in systemic lupus erythematosus

2012 ◽  
Vol 64 (9) ◽  
pp. 2947-2952 ◽  
Author(s):  
Corinna E. Weckerle ◽  
Dorothy Mangale ◽  
Beverly S. Franek ◽  
Jennifer A. Kelly ◽  
Marissa Kumabe ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Tumor Necrosis ◽  
Large Scale ◽  
Tumor Necrosis Factor Α ◽  
Scale Analysis ◽  
Systemic Lupus ◽  
Large Scale Analysis ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Variation in the ICAM1–ICAM4–ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries

2012 ◽  
Vol 71 (11) ◽  
pp. 1809-1814 ◽  
Author(s):  
Kwangwoo Kim ◽  
Elizabeth E Brown ◽  
Chan-Bum Choi ◽  
Marta E Alarcón-Riquelme ◽  
Jennifer A Kelly ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Large Scale ◽  
Meta Analysis ◽  
Gene Interaction ◽  
Nucleotide Polymorphisms ◽  
Systemic Lupus ◽  
Intracellular Adhesion Molecule ◽  
Single Marker ◽  
Genetic And Environmental Factors

ObjectiveSystemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin αM (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM.MethodsThe authors examined several markers in the ICAM1–ICAM4–ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case–control study of 17 481 unrelated participants from four ancestry populations. The single-marker association and gene–gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed.ResultsThe A-allele of ICAM1–ICAM4–ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (ORmeta=1.16, 95% CI 1.11 to 1.22; p=4.88×10−10 and ORmeta=1.67, 95% CI 1.55 to 1.79; p=3.32×10−46, respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91×10−5).ConclusionThese findings are the first to suggest that an ICAM–integrin-mediated pathway contributes to susceptibility to SLE.

Chromosome 17p12-q11 harbors susceptibility loci for systemic lupus erythematosus

2004 ◽  
Vol 115 (3) ◽  
Author(s):  
CeciliaM. Johansson ◽  
Renata Zunec ◽  
MercedesA. Garc�a ◽  
HugoR. Scherbarth ◽  
GuillermoA. Tate ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Susceptibility Loci ◽  
Systemic Lupus

scholarly journals PETANDA BIOLOGIK TERKINI LUPUS NEFRITIS

2018 ◽  
Vol 20 (2) ◽  
pp. 154
Author(s):  
Hani Susianti ◽  
Kusworini Handono
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Gold Standard ◽  
Large Scale ◽  
Renal Damage ◽  
Systemic Lupus ◽  
Urine Sediment ◽  
Early Relapse ◽  
Prognostic Stratification ◽  
Novel Biomarkers

Lupus Nephritis (LN) is one of the serious clinical manifestation of Systemic Lupus Erythematosus (SLE). Early detection and treatmentof renal activity may spare patients from renal damage. Conventional biomarkers such as urine sediment, proteinuria, creatinine, antidsDNA antibody and their complement levels are not specific and sensitive enough in detecting the ongoing disease activity in the lupuskidneys and early relapse of nephritis. Renal biopsy is the gold standard in providing information on the histopathology of LN, but isinvasive and it should take a serial of biopsies making it impractical when monitoring LN. Thus, some novel biomarkers are necessary toenhance the diagnostic accuracy and sensitivity of lupus renal disease, prognostic stratification, monitoring of treatment response anddetection of early renal flares as well. Some novel biomarkers have been studied in LN, however, validation on a large scale of patientswith different ethnic backgrounds is still needed.

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