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Transmission disequilibrium analysis of whole genome data in childhood-onset systemic lupus erythematosus

Genes & Immunity volume 24, pages 200–206 (2023)Cite this article

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Abstract

Childhood-onset systemic lupus erythematosus (cSLE) patients are unique, with hallmarks of Mendelian disorders (early-onset and severe disease) and thus are an ideal population for genetic investigation of SLE. In this study, we use the transmission disequilibrium test (TDT), a family-based genetic association analysis that employs robust methodology, to analyze whole genome sequencing data. We aim to identify novel genetic associations in an ancestrally diverse, international cSLE cohort. Forty-two cSLE patients and 84 unaffected parents from 3 countries underwent whole genome sequencing. First, we performed TDT with single nucleotide variant (SNV)-based (common variants) using PLINK 1.9, and gene-based (rare variants) analyses using Efficient and Parallelizable Association Container Toolbox (EPACTS) and rare variant TDT (rvTDT), which applies multiple gene-based burden tests adapted for TDT, including the burden of rare variants test. Applying the GWAS standard threshold (5.0 × 10−8) to common variants, our SNV-based analysis did not return any genome-wide significant SNVs. The rare variant gene-based TDT analysis identified many novel genes significantly enriched in cSLE patients, including HNRNPUL2, a DNA repair protein, and DNAH11, a ciliary movement protein, among others. Our approach identifies several novel SLE susceptibility genes in an ancestrally diverse childhood-onset lupus cohort.

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Data availability

The data from this paper are available from the corresponding author upon reasonable request.

References

  1. AlE'ed A, Vega-Fernandez P, Muscal E, Hinze CH, Tucker LB, Appenzeller S, et al. Challenges of diagnosing cognitive dysfunction with neuropsychiatric systemic lupus erythematosus in childhood. Arthritis Care Res. 2017;69:1449–59.

    Article  Google Scholar 

  2. Ardoin SP, Schanberg LE. Lessons from SLE: children are not little adults. Nat Rev Rheumatol. 2012;8:444–5.

    Article  PubMed  Google Scholar 

  3. Vazzana KM, Daga A, Goilav B, Ogbu EA, Okamura DM, Park C, et al. Principles of pediatric lupus nephritis in a prospective contemporary multi-center cohort. Lupus. 2021;30:1660–70.

    Article  PubMed  Google Scholar 

  4. Lewandowski LB, Schanberg LE Chapter 22 - Systemic lupus erythematosus in children. In: Lahita RG, Costenbader KH, Bucala R, Manzi S, Khamashta MA, editors. Lahita’s Systemic Lupus Erythematosus (Sixth Edition). San Diego: Academic Press; 2021. p. 365–80.

  5. Brunner HI, Gladman DD, Ibañez D, Urowitz MD, Silverman ED. Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum. 2008;58:556–62.

    Article  PubMed  Google Scholar 

  6. Livingston B, Bonner A, Pope J. Differences in clinical manifestations between childhood-onset lupus and adult-onset lupus: a meta-analysis. Lupus. 2011;20:1345–55.

    Article  CAS  PubMed  Google Scholar 

  7. Hiraki LT, Silverman ED. Genomics of systemic lupus erythematosus: insights gained by studying monogenic young-onset systemic lupus erythematosus. Rheum Dis Clin North Am. 2017;43:415–34.

    Article  PubMed  Google Scholar 

  8. Hiraki LT, Feldman CH, Liu J, Alarcon GS, Fischer MA, Winkelmayer WC, et al. Prevalence, incidence, and demographics of systemic lupus erythematosus and lupus nephritis from 2000 to 2004 among children in the US Medicaid beneficiary population. Arthritis Rheum. 2012;64:2669–76.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lo MS. Monogenic lupus. Curr Rheumatol Rep. 2016;18:71.

    Article  PubMed  Google Scholar 

  10. Deafen D, Escalante A, Weinrib L, Horwitz D, Bachman B, Roy‐Burman P, et al. A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum. 1992;35:311–8.

    Article  Google Scholar 

  11. Sestak AL, Shaver TS, Moser KL, Neas BR, Harley JB. Familial aggregation of lupus and autoimmunity in an unusual multiplex pedigree. J Rheumatol. 1999;26:1495–9.

    CAS  PubMed  Google Scholar 

  12. Webber D, Cao J, Dominguez D, Gladman DD, Levy DM, Ng L, et al. Association of systemic lupus erythematosus (SLE) genetic susceptibility loci with lupus nephritis in childhood-onset and adult-onset SLE. Rheumatol (Oxf). 2020;59:90–8.

    Article  Google Scholar 

  13. Wong M, Tsao BP. Current topics in human SLE genetics. Springe Semin Immunopathol. 2006;28:97–107.

    Article  CAS  Google Scholar 

  14. Bentham J, Morris DL, Cunninghame Graham DS, Pinder CL, Tombleson P, Behrens TW, et al. Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus. Nat Genet. 2015;47:1457–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Dominguez D, Kamphuis S, Beyene J, Wither J, Harley JB, Blanco I, et al. Relationship between genetic risk and age of diagnosis in systemic lupus erythematosus. J Rheumatol. 2021;48:852–8.

    Article  CAS  PubMed  Google Scholar 

  16. Omarjee O, Picard C, Frachette C, Moreews M, Rieux-Laucat F, Soulas-Sprauel P, et al. Monogenic lupus: dissecting heterogeneity. Autoimmun Rev. 2019;18:102361.

    Article  CAS  PubMed  Google Scholar 

  17. Misztal MC, Liao F, Couse M, Cao J, Dominguez D, Lau L, et al. Genome-Wide Sequencing Identified Rare Genetic Variants for Childhood-Onset Monogenic Lupus. J Rheumatol. 2023;50:671–5.

    Article  PubMed  Google Scholar 

  18. Bryan AR, Wu EY. Complement deficiencies in systemic lupus erythematosus. Curr Allergy Asthma Rep. 2014;14:448.

    Article  PubMed  Google Scholar 

  19. Lee-Kirsch MA, Chowdhury D, Harvey S, Gong M, Senenko L, Engel K, et al. A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus. J Mol Med (Berl, Ger). 2007;85:531–7.

    Article  CAS  Google Scholar 

  20. Al-Mayouf SM, Sunker A, Abdwani R, Abrawi SA, Almurshedi F, Alhashmi N, et al. Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus. Nat Genet. 2011;43:1186–8.

    Article  CAS  PubMed  Google Scholar 

  21. Brown GJ, Cañete PF, Wang H, Medhavy A, Bones J, Roco JA, et al. TLR7 gain-of-function genetic variation causes human lupus. Nature. 2022;605:349–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Batu ED, Kosukcu C, Taskiran E, Sahin S, Akman S, Sözeri B, et al. Whole exome sequencing in early-onset systemic lupus erythematosus. J Rheumatol. 2018;45:1671–9.

    Article  CAS  PubMed  Google Scholar 

  23. Tirosh I, Spielman S, Barel O, Ram R, Stauber T, Paret G, et al. Whole exome sequencing in childhood-onset lupus frequently detects single gene etiologies. Pediatr Rheumatol. 2019;17:52.

    Article  Google Scholar 

  24. Ewens WJ, Spielman RS. The transmission/disequilibrium test: history, subdivision, and admixture. Am J Hum Genet. 1995;57:455.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Rogers AJ, Weiss ST. Epidemiologic and population genetic studies. Clinical and Translational Science: Elsevier; 2017. p. 313–26.

  26. Barbosa FB, Cagnin NF, Simioni M, Farias AA, Torres FR, Molck MC, et al. Ancestry informative marker panel to estimate population stratification using genome-wide human array. Ann Hum Genet. 2017;81:225–33.

    Article  CAS  PubMed  Google Scholar 

  27. Shriner D, Adeyemo A, Ramos E, Chen G, Rotimi CN. Mapping of disease-associated variants in admixed populations. Genome Biol. 2011;12:223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Laird NM, Lange C. Family-based designs in the age of large-scale gene-association studies. Nat Rev Genet. 2006;7:385–94.

    Article  CAS  PubMed  Google Scholar 

  29. Sillanpää MJ. Overview of techniques to account for confounding due to population stratification and cryptic relatedness in genomic data association analyses. Heredity (Edinb). 2011;106:511–9.

    Article  PubMed  Google Scholar 

  30. Liu J, Lewinger JP, Gilliland FD, Gauderman WJ, Conti DV. Confounding and heterogeneity in genetic association studies with admixed populations. Am J Epidemiol. 2013;177:351–60.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Tsuchiya N, Kawasaki A, Tsao B, Komata T, Grossman J, Tokunaga K. Analysis of the association of HLA-DRB1, TNFα promoter and TNFR2 (TNFRSF1B) polymorphisms with SLE using transmission disequilibrium test. Genes Immun. 2001;2:317–22.

    Article  CAS  PubMed  Google Scholar 

  32. Jacob CO, Reiff A, Armstrong DL, Myones BL, Silverman E, Klein-Gitelman M, et al. Identification of novel susceptibility genes in childhood-onset systemic lupus erythematosus using a uniquely designed candidate gene pathway platform. Arthritis Rheum. 2007;56:4164–73.

    Article  CAS  PubMed  Google Scholar 

  33. Hernandez RD, Uricchio LH, Hartman K, Ye C, Dahl A, Zaitlen N. Ultrarare variants drive substantial cis heritability of human gene expression. Nat Genet. 2019;51:1349–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.

    Article  CAS  PubMed  Google Scholar 

  35. Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29:288–91.

    PubMed  Google Scholar 

  36. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990;215:403–10.

    Article  CAS  PubMed  Google Scholar 

  37. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20:1297–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Team RC. R: A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2017.

  40. Gogarten SM, Sofer T, Chen H, Yu C, Brody JA, Thornton TA, et al. Genetic association testing using the GENESIS R/Bioconductor package. Bioinforma (Oxf, Engl). 2019;35:5346–8.

    CAS  Google Scholar 

  41. Altshuler DM, Gibbs RA, Peltonen L, Altshuler DM, Gibbs RA, Peltonen L, et al. Integrating common and rare genetic variation in diverse human populations. Nature. 2010;467:52–8.

    Article  CAS  PubMed  Google Scholar 

  42. Alexander DH, Novembre J, Lange K. Fast model-based estimation of ancestry in unrelated individuals. Genome Res. 2009;19:1655–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. He Z, O'Roak BJ, Smith JD, Wang G, Hooker S, Santos-Cortez RL, et al. Rare-variant extensions of the transmission disequilibrium test: application to autism exome sequence data. Am J Hum Genet. 2014;94:33–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Risch N, Merikangas K. The future of genetic studies of complex human diseases. Sci (N. Y, NY). 1996;273:1516–7.

    Article  CAS  Google Scholar 

  45. Pe'er I, Yelensky R, Altshuler D, Daly MJ. Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet Epidemiol. 2008;32:381–5.

    Article  PubMed  Google Scholar 

  46. Kang, H. M. EPACTS (efficient and parallelizable association container toolbox). 2012. https://genome.sph.umich.edu/wiki/EPACTS.

  47. Auer PL, Wang G, Leal SM. Testing for rare variant associations in the presence of missing data. Genet Epidemiol. 2013;37:529–38.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Li B, Leal SM. Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data. Am J Hum Genet. 2008;83:311–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Price AL, Kryukov GV, de Bakker PI, Purcell SM, Staples J, Wei L-J, et al. Pooled association tests for rare variants in exon-resequencing studies. Am J Hum Genet. 2010;86:832–8.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Lee S, Abecasis GR, Boehnke M, Lin X. Rare-variant association analysis: study designs and statistical tests. Am J Hum Genet. 2014;95:5–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yu HH, Lee JH, Wang LC, Yang YH, Chiang BL. Neuropsychiatric manifestations in pediatric systemic lupus erythematosus: a 20-year study. Lupus. 2006;15:651–7.

    Article  CAS  PubMed  Google Scholar 

  52. Gkirtzimanaki K, Kabrani E, Nikoleri D, Polyzos A, Blanas A, Sidiropoulos P, et al. IFNα impairs autophagic degradation of mtDNA promoting autoreactivity of SLE monocytes in a STING-dependent fashion. Cell Rep. 2018;25:921–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Alarcón‐Segovia D, Alarcón‐Riquelme ME, Cardiel MH, Caeiro F, Massardo L, Villa AR, et al. Familial aggregation of systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases in 1177 lupus patients from the GLADEL cohort. Arthritis Rheumatol. 2005;52:1138–47.

    Google Scholar 

  54. Budarf ML, Goyette P, Boucher G, Lian J, Graham RR, Claudio JO, et al. A targeted association study in systemic lupus erythematosus identifies multiple susceptibility alleles. Genes Immun. 2011;12:51–8.

    Article  CAS  PubMed  Google Scholar 

  55. Bronson PG, Komorowski LK, Ramsay PP, May SL, Noble J, Lane JA, et al. Analysis of maternal–offspring HLA compatibility, parent‐of‐origin effects, and noninherited maternal antigen effects for HLA–DRB1 in systemic lupus erythematosus. Arthritis Rheum. 2010;62:1712–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Moser KL, Kelly JA, Lessard CJ, Harley JB. Recent insights into the genetic basis of systemic lupus erythematosus. Genes Immun. 2009;10:373–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Peschken CA. Health disparities in systemic lupus erythematosus. Rheum Dis Clin. 2020;46:673–83.

    Article  Google Scholar 

  58. Pullmann R Jr, Bonilla E, Phillips PE, Middleton FA, Perl A. Haplotypes of the HRES-1 endogenous retrovirus are associated with development and disease manifestations of systemic lupus erythematosus. Arthritis Rheum. 2008;58:532–40.

    Article  CAS  PubMed  Google Scholar 

  59. Liu JL, Zhang FY, Liang YH, Xiao FL, Zhang SQ, Cheng YL, et al. Association between the PD1. 3A/G polymorphism of the PDCD1 gene and systemic lupus erythematosus in European populations: a meta‐analysis. J Eur Acad Dermatol Venereol. 2009;23:425–32.

    Article  PubMed  Google Scholar 

  60. Polo Sophie E, Blackford Andrew N, Chapman JR, Baskcomb L, Gravel S, Rusch A, et al. Regulation of DNA-end resection by hnRNPU-like proteins promotes DNA double-strand break signaling and repair. Mol Cell. 2012;45:505–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Jiang H, Wang Y, Ai M, Wang H, Duan Z, Wang H, et al. Long noncoding RNA CRNDE stabilized by hnRNPUL2 accelerates cell proliferation and migration in colorectal carcinoma via activating Ras/MAPK signaling pathways. Cell Death Dis. 2017;8:e2862.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Calender A, Rollat Farnier PA, Buisson A, Pinson S, Bentaher A, Lebecque S, et al. Whole exome sequencing in three families segregating a pediatric case of sarcoidosis. BMC Med Genom. 2018;11:23.

    Article  Google Scholar 

  63. Knowles MR, Leigh MW, Carson JL, Davis SD, Dell SD, Ferkol TW, et al. Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure. Thorax. 2012;67:433–41.

    Article  PubMed  Google Scholar 

  64. Schultz R, Elenius V, Lukkarinen H, Saarela T. Two novel mutations in the DNAH11 gene in primary ciliary dyskinesia (CILD7) with considerable variety in the clinical and beating cilia phenotype. BMC Med Genet. 2020;21:1–7.

    Article  Google Scholar 

  65. Xiong Y, Xia H, Yuan L, Deng S, Ding Z, Deng H. Identification of compound heterozygous DNAH11 variants in a Han-Chinese family with primary ciliary dyskinesia. J Cell Mol Med. 2021;25:9028–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Tsyklauri O, Niederlova V, Forsythe E, Prasai A, Drobek A, Kasparek P, et al. Bardet–Biedl syndrome ciliopathy is linked to altered hematopoiesis and dysregulated self-tolerance. EMBO Rep. 2021;22:e50785.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Cassioli C, Baldari CT. A ciliary view of the immunological synapse. Cells. 2019;8:789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Alagramam KN, Miller ND, Adappa ND, Pitts DR, Heaphy JC, Yuan H, et al. Promoter, alternative splice forms, and genomic structure of protocadherin 15. Genomics. 2007;90:482–92.

    Article  CAS  PubMed  Google Scholar 

  69. Albertin CB, Simakov O, Mitros T, Wang ZY, Pungor JR, Edsinger-Gonzales E, et al. The octopus genome and the evolution of cephalopod neural and morphological novelties. Nature. 2015;524:220–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Wang X, Su H, Bradley A. Molecular mechanisms governing Pcdh-gamma gene expression: evidence for a multiple promoter and cis-alternative splicing model. Genes Dev. 2002;16:1890–905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Haas CS, Creighton CJ, Pi X, Maine I, Koch AE, Haines GK, et al. Identification of genes modulated in rheumatoid arthritis using complementary DNA microarray analysis of lymphoblastoid B cell lines from disease-discordant monozygotic twins. Arthritis Rheum. 2006;54:2047–60.

    Article  CAS  PubMed  Google Scholar 

  72. Zeng Y, Zhao K, Oros Klein K, Shao X, Fritzler MJ, Hudson M, et al. Thousands of CpGs show DNA methylation differences in ACPA-positive individuals. Genes. 2021;12:1349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Murthy SE, Dubin AE, Whitwam T, Jojoa-Cruz S, Cahalan SM, Mousavi SAR, et al. OSCA/TMEM63 are an evolutionarily conserved family of mechanically activated ion channels. Elife. 2018;7:e41844.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Yan H, Helman G, Murthy SE, Ji H, Crawford J, Kubisiak T, et al. Heterozygous variants in the mechanosensitive ion channel TMEM63A result in transient hypomyelination during infancy. Am J Hum Genet. 2019;105:996–1004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kaiser FM, Gruenbacher S, Oyaga MR, Nio E, Jaritz M, Sun Q, et al. Biallelic PAX5 mutations cause hypogammaglobulinemia, sensorimotor deficits, and autism spectrum disorder. J Exp Med. 2022;219:e20220498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Morris DL, Taylor KE, Fernando MM, Nititham J, Alarcón-Riquelme ME, Barcellos LF, et al. Unraveling multiple MHC gene associations with systemic lupus erythematosus: model choice indicates a role for HLA alleles and non-HLA genes in Europeans. Am J Hum Genet. 2012;91:778–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Sirikong M, Tsuchiya N, Chandanayingyong D, Bejrachandra S, Suthipinittharm P, Luangtrakool K, et al. Association of HLA-DRB1*1502-DQB1*0501 haplotype with susceptibility to systemic lupus erythematosus in Thais. Tissue Antigens. 2002;59:113–7.

    Article  CAS  PubMed  Google Scholar 

  78. Langefeld CD, Ainsworth HC, Cunninghame Graham DS, Kelly JA, Comeau ME, Marion MC, et al. Transancestral mapping and genetic load in systemic lupus erythematosus. Nat Commun. 2017;8:16021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Jiang SH, Athanasopoulos V, Ellyard JI, Chuah A, Cappello J, Cook A, et al. Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus. Nat Commun. 2019;10:2201.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Niewold TB. Advances in lupus genetics. Curr Opin Rheumatol. 2015;27:440–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Warrier V, Toro R, Chakrabarti B, Børglum AD, Grove J, Hinds DA, et al. Genome-wide analyses of self-reported empathy: correlations with autism, schizophrenia, and anorexia nervosa. Transl Psychiatry. 2018;8:35.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Howe AS, Buttenschøn HN, Bani-Fatemi A, Maron E, Otowa T, Erhardt A, et al. Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways. Mol Psychiatry. 2016;21:665–79.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank all the cSLE patients and their families for participation in this study. We are grateful to Michael Ombrello for his thoughtful review of this manuscript, and Yolanda L. Jones, National Institutes of Health Library, for manuscript review and editing. This work utilized the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov).

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Authors and Affiliations

  1. Lupus Genomics and Global Health Disparities Unit, Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA

    Kathleen M. Vazzana & Laura B. Lewandowski

  2. Arnold Palmer Hospital for Children, Orlando, FL, USA

    Kathleen M. Vazzana

  3. Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, 22124, USA

    Anthony M. Musolf & Joan E. Bailey-Wilson

  4. Division of Rheumatology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Linda T. Hiraki & Earl D. Silverman

  5. Paediatric Rheumatology, Red Cross War Memorial Children’s Hospital and University of Cape Town, Cape Town, South Africa

    Christiaan Scott

  6. The American Genome Center, Department of Anatomy, Physiology & Genetics, Uniformed Services University, Bethesda, MD, USA

    Clifton L. Dalgard

  7. Clinical Program, Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA

    Sarfaraz Hasni

  8. Biodata Mining and Discovery Section, Office of Science and Technology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA

    Zuoming Deng

  9. Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA

    Mariana J. Kaplan

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  1. Kathleen M. Vazzana
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Contributions

LBL, SH, and MK designed the clinical protocol. CD performed the sequencing protocol. LBL, KV, AM, and JEBW designed the research methodology. ZD, LBL and AM performed the data analysis. LBL, KV, and AM wrote the manuscript. KV, LH, CS, AB, ZD, CD, JEBW, AM, SH, MK and LBL reviewed and revised the full manuscript.

Corresponding author

Correspondence to Laura B. Lewandowski.

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Competing interests

The authors have no conflicts of interest to declare. KV, LBL, SH, ZD, CD, and MK were funded by the National Institute of Arthritis Musculoskeletal and Skin Diseases Intramural research program. AMM and JEBW were funded by the National Human Genome Research Institute Intramural research program of the National Institutes of Health. LH was funded by US Department of Defense Idea Award and a Canada Research Chair Tier 2 Award.

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Vazzana, K.M., Musolf, A.M., Bailey-Wilson, J.E. et al. Transmission disequilibrium analysis of whole genome data in childhood-onset systemic lupus erythematosus. Genes Immun 24, 200–206 (2023). https://doi.org/10.1038/s41435-023-00214-x

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