ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0908

Clinical Characteristics of Patients with High SLE-specific and High Multitrait Polygenic Risk – an Investigation of SLE Risk Loci

Nina Oparina1, Sarah Reid2, Ahmed Sayadi3, Maija-Leena Eloranta4, Martina Frodlund5, Karoline Lerang6, Andreas Jönsen7, Solbritt Rantapaa-Dahlqvist8, Anders Bengtsson7, Anna Rudin9, Øyvind Molberg10, Christopher Sjowall11, Lars Rönnblom4 and Dag Leonard4, 1UU, Uppsala, Sweden, 2Uppsala University, Medical Sciences, Uppsala, Sweden, 3Uppsala, Uppsala, Sweden, 4Uppsala University, Uppsala, Sweden, 5Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Rheumatology, Linköping University, Linköping, Sweden, 6Oslo University, Oslo, Norway, 7Lund University, Lund, Sweden, 8Umeå University, Umeå, Sweden, 9Institute of Medicine, University of Gothenburg, Gothenburg, Sweden, 10Department of Rheumatology, Oslo University Hospital, Rikshospitalet, Oslo, Norway, 11Linköping University, Linköping, Sweden

Meeting: ACR Convergence 2024

Keywords: , ,

Session Information

Date: Sunday, November 17, 2024

Title: Genetics, Genomics & Proteomics Poster

Session Type: Poster Session B

Session Time: 10:30AM-12:30PM

Background/Purpose: Heritability of SLE is high and more than 200 genetically associated SLE risk loci were identified. Part of them  are specific and associate with SLE development only while other associate with other diseases, such as type 1 diabetes (T1DM) and rheumatoid arthritis (RA). Our objective: to investigate what clinical phenotype associate with high polygenic scores (PRSs) for SLE-specific and multitrait-associated SLE loci.

Methods: Patients with SLE (ACR-97 or SLICC-12, n=1498) and healthy controls (n=1947) were genotyped using Illumina’s Global Screening Array. SLE-associated single nucleotide variants (SNVs) (European ancestry) at GWAS significance (p< 5×10-8) were identified through the GWAS catalog. After filtering 112 SNVs were identified. SNVs were considered multitrait if associated with ≥1 additional disease. Two PRSs were constructed; one including SLE specific SNVs (n=79) and one including multitrait SNVs (n=33). Groups were compared using logistic regression, adjusting for age and sex. 50% of patients with the highest SLE-specific PRS were selected and from them the 50% with the lowest multitrait PRS were selected. This group (highSLE-lowMultitrait, 25% of total) was then compared with the other patients (75% of total). The same method was used for the highMultitrait-lowSLE group.

Results: Both PRSs were higher in patients in comparison with healthy controls, p< 2×10-6. Besides SLE, the most common diseases associated with the multitrait SNVs were RA (SNV=10), T1DM (SNV=8), multiple sclerosis and ulcerative colitis (SNV=6).

The highSLE-lowMultitrait group had higher prevalence of malar rash (OR 1.28(1.00-1.66), p=0.04), neurologic manifestations (OR 1.44(1.10-2.08), p=0.048), thrombocytopenia (OR 1.47(1.06-2.04), p=0.022), anti-Sm antibodies (OR 1.80(1.12-2.80), p=0.009), low complement (OR 1.70(1.25-2.30), p < 0.001) and lower prevalence of hemolytic anemia (OR 0.55(0.32-0.97), p=0.038) compared with the other group.

The highMultitrait-lowSLE group had higher prevalence of anti-SSA (OR 1.49 (1.14-1.94), p= 0.003) and anti-SSB antibodies (OR 1.79 (1.34-2.39), p < 0.001) and lower prevalence of discoid rash (OR 0.72(0.52-1.0), p=0.038) compared with the other group.

Conclusion: Our results shed light on SLE heterogeneity. Leveraging data for shared genetic associations can be important for determining the genetic background influencing SLE subphenotypes, but also common disease manifestations among autoimmune diseases.

Disclosures: N. Oparina: None; S. Reid: None; A. Sayadi: None; M. Eloranta: None; M. Frodlund: None; K. Lerang: None; A. Jönsen: None; S. Rantapaa-Dahlqvist: None; A. Bengtsson: None; A. Rudin: None; Ø. Molberg: None; C. Sjowall: Bristol-Myers Squibb(BMS), 3; L. Rönnblom: Ampel Biosolutions, 1, AstraZeneca, 1, 6, Bayer, 2, BMS, 1, UCB, 1; D. Leonard: AstraZeneca, 1.

To cite this abstract in AMA style:

Oparina N, Reid S, Sayadi A, Eloranta M, Frodlund M, Lerang K, Jönsen A, Rantapaa-Dahlqvist S, Bengtsson A, Rudin A, Molberg Ø, Sjowall C, Rönnblom L, Leonard D. Clinical Characteristics of Patients with High SLE-specific and High Multitrait Polygenic Risk – an Investigation of SLE Risk Loci [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/clinical-characteristics-of-patients-with-high-sle-specific-and-high-multitrait-polygenic-risk-an-investigation-of-sle-risk-loci/. Accessed .

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