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O4 Clinical characteristics of patients with high SLE-specific and high multitrait polygenic risk – An investigation of SLE risk loci
  1. Nina Oparina1,
  2. Sarah Reid1,
  3. Ahmed Sayadi1,
  4. Maija-Leena Eloranta1,
  5. Martina Frodlund2,
  6. Karoline Lerang3,
  7. Andreas Jönsen4,
  8. Solbritt Rantapää-Dahlqvist5,
  9. Anders A Bengtsson4,
  10. Anna Rudin6,
  11. Øyvind Molberg3,
  12. Christopher Sjöwall2,
  13. Lars Rönnblom1 and
  14. Dag Leonard1
  1. 1Dept. of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden
  2. 2Dept. of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Rheumatology, Linköping University, Linköping, Sweden
  3. 3Dept. of Rheumatology, Oslo University Hospital, Oslo, Norway
  4. 4Dept. of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden
  5. 5Dept. of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden
  6. 6Dept. of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Abstract

Objective Some genome-wide significant SLE risk loci 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.

Conclusions Comparative analysis of multitrait and SLE-specific SNVs 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.

Acknowledgements Supported by the Swedish Society for Medical Research (S20–0127), the Swedish Rheumatism Association, King Gustaf V’s 80-Year Foundation, the Gustafsson Foundation.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ .

https://doi.org/10.1136/lupus-2024-el.14

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