Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Communication
  • Published:

European population substructure correlates with systemic lupus erythematosus endophenotypes in North Americans of European descent

Genes & Immunity volume 11, pages 515–521 (2010)Cite this article

Abstract

Previous work has demonstrated that Northern and Southern European ancestries are associated with specific systemic lupus erythematosus (SLE) manifestations. In this study, 1855 SLE cases of European descent were genotyped for 4965 single-nucleotide polymorphisms and principal components analysis of genotype information was used to define population substructure. The first principal component (PC1) distinguished Northern from Southern European ancestry, PC2 differentiated Eastern from Western European ancestry and PC3 delineated Ashkenazi Jewish ancestry. Compared with Northern European ancestry, Southern European ancestry was associated with autoantibody production (odds ratio (OR)=1.40, 95% confidence interval (CI) 1.07–1.83) and renal involvement (OR 1.41, 95% CI 1.06–1.87), and was protective for discoid rash (OR=0.51, 95% CI 0.32–0.82) and photosensitivity (OR=0.74, 95% CI 0.56–0.97). Both serositis (OR=1.46, 95% CI 1.12–1.89) and autoantibody production (OR=1.38, 95% CI 1.06–1.80) were associated with Western compared to Eastern European ancestry. Ashkenazi Jewish ancestry was protective against neurologic manifestations of SLE (OR=0.62, 95% CI 0.40–0.94). Homogeneous clusters of cases defined by multiple PCs demonstrated stronger phenotypic associations. Genetic ancestry may contribute to the development of SLE endophenotypes and should be accounted for in genetic studies of disease characteristics.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.

    Article  CAS  Google Scholar 

  2. Siegel M, Reilly EB, Lee SL, Fuerst HT, Seelenfreund M . Epidemiology of systemic lupus erythematosus: time trend and racial differences. Am J Public Health 1964; 54: 33–43.

    Article  CAS  Google Scholar 

  3. Alarcon GS, McGwin Jr G, Petri M, Reveille JD, Ramsey-Goldman R, Kimberly RP . Baseline characteristics of a multiethnic lupus cohort: PROFILE. Lupus 2002; 11: 95–101.

    Article  CAS  Google Scholar 

  4. Alarcon GS, Friedman AW, Straaton KV, Moulds JM, Lisse J, Bastian HM et al. Systemic lupus erythematosus in three ethnic groups: III. A comparison of characteristics early in the natural history of the LUMINA cohort. LUpus in MInority populations: NAture vs Nurture. Lupus 1999; 8: 197–209.

    Article  CAS  Google Scholar 

  5. Seldin MF, Qi L, Scherbarth HR, Tian C, Ransom M, Silva G et al. Amerindian ancestry in Argentina is associated with increased risk for systemic lupus erythematosus. Genes Immun 2008; 9: 389–393.

    Article  CAS  Google Scholar 

  6. Alarcon GS, Bastian HM, Beasley TM, Roseman JM, Tan FK, Fessler BJ et al. Systemic lupus erythematosus in a multi-ethnic cohort (LUMINA) XXXII: [corrected] contributions of admixture and socioeconomic status to renal involvement. Lupus 2006; 15: 26–31.

    Article  CAS  Google Scholar 

  7. Cavalli-Sforza LL, Menozzi P, Piazza A . Demic expansions and human evolution. Science (New York, N.Y) 1993; 259: 639–646.

    Article  CAS  Google Scholar 

  8. Novembre J, Johnson T, Bryc K, Kutalik Z, Boyko AR, Auton A et al. Genes mirror geography within Europe. Nature 2008; 456: 98–101.

    Article  CAS  Google Scholar 

  9. Seldin MF, Shigeta R, Villoslada P, Selmi C, Tuomilehto J, Silva G et al. European population substructure: clustering of northern and southern populations. PLoS Genetics 2006; 2: e143.

    Article  Google Scholar 

  10. Chung SA, Tian C, Taylor KE, Lee AT, Ortmann WA, Hom G et al. European population substructure is associated with mucocutaneous manifestations and autoantibody production in systemic lupus erythematosus. Arthritis Rheum 2009; 60: 2448–2456.

    Article  Google Scholar 

  11. Tian C, Plenge RM, Ransom M, Lee A, Villoslada P, Selmi C et al. Analysis and application of European genetic substructure using 300 K SNP information. PLoS Genetics 2008; 4: e4.

    Article  Google Scholar 

  12. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D . Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 2006; 38: 904–909.

    Article  CAS  Google Scholar 

  13. Hom G, Graham RR, Modrek B, Taylor KE, Ortmann W, Garnier S et al. Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med 2008; 358: 900–909.

    Article  CAS  Google Scholar 

  14. Lao O, Lu TT, Nothnagel M, Junge O, Freitag-Wolf S, Caliebe A et al. Correlation between genetic and geographic structure in Europe. Curr Biol 2008; 18: 1241–1248.

    Article  CAS  Google Scholar 

  15. Danchenko N, Satia JA, Anthony MS . Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus 2006; 15: 308–318.

    Article  CAS  Google Scholar 

  16. Ferreiros-Vidal I, D′Alfonso S, Papasteriades C, Skopouli FN, Marchini M, Scorza R et al. Bias in association studies of systemic lupus erythematosus susceptibility due to geographical variation in the frequency of a programmed cell death 1 polymorphism across Europe. Genes Immun 2007; 8: 138–146.

    Article  CAS  Google Scholar 

  17. Lee YH, Woo JH, Choi SJ, Ji JD, Song GG . Association of programmed cell death 1 polymorphisms and systemic lupus erythematosus: a meta-analysis. Lupus 2009; 18: 9–15.

    Article  CAS  Google Scholar 

  18. Gregersen PK, Lee HS, Batliwalla F, Begovich AB . PTPN22: setting thresholds for autoimmunity. Semin Immunol 2006; 18: 214–223.

    Article  CAS  Google Scholar 

  19. Mitchell MK, Gregersen PK, Johnson S, Parsons R, Vlahov D . The New York Cancer Project: rationale, organization, design, and baseline characteristics. J Urban Health 2004; 81: 301–310.

    Article  Google Scholar 

  20. Kosoy R, Nassir R, Tian C, White PA, Butler LM, Silva G et al. Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America. Hum Mutat 2009; 30: 69–78.

    Article  Google Scholar 

Download references

Acknowledgements

This work has been supported by NIH/NIAMS grants P60 AR053308, K24 AR02175, R01 AR052300, and a Kirkland Scholar Award to Dr Criswell; NIH/NIAMS and NIH/NIAID grants R01 AI68759 and N01 AR1–2256 to Dr Gregersen; NIH/NIAMS grants R01 AR46588–05 and K24 AR002213-05 to Dr Manzi; and NIH/NIAMS grant R01 AR050267 to Dr Seldin. These studies were performed in part in the University of California, San Francisco, General Clinical Research Center (Moffitt Hospital), the University of Pittsburgh General Clinical Research Center and the Johns Hopkins University General Clinical Research Center with funds provided by the US Public Health Service National Center for Research Resources, M01 RR-00079, M01 RR-000056 and M01 RR-00052. This publication was also supported by NIH/NCRR/OD UCSF-CTSI grant number TL1 RR024129. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Author information

Authors and Affiliations

  1. Division of Rheumatology, Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, San Francisco, CA, USA,

    I B Richman, S A Chung, K E Taylor, J Nititham & L A Criswell

  2. Department of Biochemistry and Molecular Medicine, Rowe Program in Genetics, University of California, Davis, Davis, CA, USA,

    R Kosoy, C Tian & M F Seldin

  3. Immunology Diagnostics and Biomarkers, Genentech Inc., South San Francisco, CA, USA

    W A Ortmann & T W Behrens

  4. Robert S Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA

    A T Lee & P K Gregersen

  5. Division of Rheumatology and Clinical Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    S Rutman & S Manzi

  6. Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    M Petri

Authors
  1. I B Richman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S A Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K E Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R Kosoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. W A Ortmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J Nititham
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A T Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S Rutman
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M Petri
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. S Manzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. T W Behrens
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. P K Gregersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. M F Seldin
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. L A Criswell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L A Criswell.

Ethics declarations

Competing interests

Dr Behrens and Mr Ortmann are employees of Genentech.

Additional information

Supplementary Information accompanies the paper on Genes and Immunity website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Richman, I., Chung, S., Taylor, K. et al. European population substructure correlates with systemic lupus erythematosus endophenotypes in North Americans of European descent. Genes Immun 11, 515–521 (2010). https://doi.org/10.1038/gene.2009.80

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/gene.2009.80

Keywords

This article is cited by

Search

Advanced search

Quick links