Objective: Specific risk alleles for childhood-onset systemic lupus erythematosus SLE (cSLE) vs adult-onset SLE (aSLE) patients have not been identified. The aims of this study were to determine if there is an association (1) between non-HLA-related genetic risk score (GRS) and age of SLE diagnosis, and (2) between HLA-related GRS and age of SLE diagnosis.
Methods: Genomic DNA was obtained from 2001 multiethnic patients and genotyped using the Immunochip. Following quality control, genetic risk counting (GRCS), weighted (GRWS), standardized counting (GRSCS), and standardized weighted (GRSWS) scores were calculated based on independent single-nucleotide polymorphisms from validated SLE loci. Scores were analyzed in a regression model and adjusted by sex and ancestral population.
Results: The analyzed cohort consisted of 1540 patients: 1351 females and 189 males (675 cSLE and 865 aSLE). There were significant negative associations between all non-HLA GRS and age of SLE diagnosis: = 0.011 and r = 0.175 for GRWS; = 0.008 and r = 0.178 for GRSCS; = 0.002 and r = 0.176 for GRSWS (higher GRS correlated with lower age of diagnosis.) All HLA GRS showed significant positive associations with age of diagnosis: = 0.049 and r = 0.176 for GRCS; = 0.022 and r = 0.176 for GRWS; = 0.022 and r = 0.176 for GRSCS; = 0.011 and r = 0.177 for GRSWS (higher GRS correlated with higher age of diagnosis).
Conclusion: Our data suggest that there is a linear relationship between genetic risk and age of SLE diagnosis and that HLA and non-HLA GRS are associated with age of diagnosis in opposite directions.
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http://dx.doi.org/10.3899/jrheum.200002 | DOI Listing |
Hereditas
January 2025
The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, No. 182 Chunhui Road, Longmatan District, Luzhou, Sichuan, 646000, China.
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Exp Hematol Oncol
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Bone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang, China.
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Mol Med
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Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, No. 8 Dianli Road, Zhenjiang, 212002, Jiangsu, People's Republic of China.
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Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
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View Article and Find Full Text PDFRandomized controlled trials (RCTs) evaluating anti-cancer agents often lack generalizability to real-world oncology patients. Although restrictive eligibility criteria contribute to this issue, the role of selection bias related to prognostic risk remains unclear. In this study, we developed TrialTranslator, a framework designed to systematically evaluate the generalizability of RCTs for oncology therapies.
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