European genetic ancestry is associated with a decreased risk of lupus nephritis

Ilana B. Richman, Kimberly E. Taylor, Sharon A. Chung, Laura Trupin, Michelle Petri, Edward Yelin, Robert R. Graham, Annette Lee, Timothy W. Behrens, Peter K. Gregersen, Michael F Seldin, Lindsey A. Criswell

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Objective. African Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than are SLE patients of European descent. This study was undertaken to investigate whether European genetic ancestry protects against the development of lupus nephritis, with the aim of exploring the genetic and socioeconomic factors that might explain this effect. Methods. This was a cross-sectional study of SLE patients from a multiethnic case collection. Participants were genotyped for 126 single-nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. Logistic regression was used to test the association between European ancestry and renal disease. Analyses were adjusted for continental ancestries, socioeconomic status (SES), and candidate genes. Results. Participants (n = 1,906) had, on average, 62.4% European, 15.8% African, 11.5% East Asian, 6.5% Amerindian, and 3.8% South Asian ancestry. Among the participants, 656 (34%) had renal disease. A 10% increase in the proportion of European ancestry estimated in each participant was associated with a 15% reduction in the odds of having renal disease, after adjustment for disease duration and sex (odds ratio 0.85, 95% confidence interval 0.82-0.87; P = 1.9 × 10-30). Adjustment for other genetic ancestries, measures of SES, or SNPs in the genes most associated with renal disease (IRF5 [rs4728142], BLK [rs2736340], STAT4 [rs3024912], and HLA-DRB10301 and DRB11501) did not substantively alter this relationship. Conclusion. European ancestry is protective against the development of renal disease in SLE, an effect that is independent of other genetic ancestries, candidate risk alleles, and socioeconomic factors.

Original languageEnglish (US)
Pages (from-to)3374-3382
Number of pages9
JournalArthritis and Rheumatism
Volume64
Issue number10
DOIs
StatePublished - Oct 2012

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Lupus Nephritis
Systemic Lupus Erythematosus
Kidney
Single Nucleotide Polymorphism
Social Class
Genes
Sex Ratio
Hispanic Americans
African Americans
Cross-Sectional Studies
Logistic Models
Alleles
Odds Ratio
Confidence Intervals

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Richman, I. B., Taylor, K. E., Chung, S. A., Trupin, L., Petri, M., Yelin, E., ... Criswell, L. A. (2012). European genetic ancestry is associated with a decreased risk of lupus nephritis. Arthritis and Rheumatism, 64(10), 3374-3382. https://doi.org/10.1002/art.34567

European genetic ancestry is associated with a decreased risk of lupus nephritis. / Richman, Ilana B.; Taylor, Kimberly E.; Chung, Sharon A.; Trupin, Laura; Petri, Michelle; Yelin, Edward; Graham, Robert R.; Lee, Annette; Behrens, Timothy W.; Gregersen, Peter K.; Seldin, Michael F; Criswell, Lindsey A.

In: Arthritis and Rheumatism, Vol. 64, No. 10, 10.2012, p. 3374-3382.

Research output: Contribution to journalArticle

Richman, IB, Taylor, KE, Chung, SA, Trupin, L, Petri, M, Yelin, E, Graham, RR, Lee, A, Behrens, TW, Gregersen, PK, Seldin, MF & Criswell, LA 2012, 'European genetic ancestry is associated with a decreased risk of lupus nephritis', Arthritis and Rheumatism, vol. 64, no. 10, pp. 3374-3382. https://doi.org/10.1002/art.34567
Richman IB, Taylor KE, Chung SA, Trupin L, Petri M, Yelin E et al. European genetic ancestry is associated with a decreased risk of lupus nephritis. Arthritis and Rheumatism. 2012 Oct;64(10):3374-3382. https://doi.org/10.1002/art.34567
Richman, Ilana B. ; Taylor, Kimberly E. ; Chung, Sharon A. ; Trupin, Laura ; Petri, Michelle ; Yelin, Edward ; Graham, Robert R. ; Lee, Annette ; Behrens, Timothy W. ; Gregersen, Peter K. ; Seldin, Michael F ; Criswell, Lindsey A. / European genetic ancestry is associated with a decreased risk of lupus nephritis. In: Arthritis and Rheumatism. 2012 ; Vol. 64, No. 10. pp. 3374-3382.
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title = "European genetic ancestry is associated with a decreased risk of lupus nephritis",
abstract = "Objective. African Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than are SLE patients of European descent. This study was undertaken to investigate whether European genetic ancestry protects against the development of lupus nephritis, with the aim of exploring the genetic and socioeconomic factors that might explain this effect. Methods. This was a cross-sectional study of SLE patients from a multiethnic case collection. Participants were genotyped for 126 single-nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. Logistic regression was used to test the association between European ancestry and renal disease. Analyses were adjusted for continental ancestries, socioeconomic status (SES), and candidate genes. Results. Participants (n = 1,906) had, on average, 62.4{\%} European, 15.8{\%} African, 11.5{\%} East Asian, 6.5{\%} Amerindian, and 3.8{\%} South Asian ancestry. Among the participants, 656 (34{\%}) had renal disease. A 10{\%} increase in the proportion of European ancestry estimated in each participant was associated with a 15{\%} reduction in the odds of having renal disease, after adjustment for disease duration and sex (odds ratio 0.85, 95{\%} confidence interval 0.82-0.87; P = 1.9 × 10-30). Adjustment for other genetic ancestries, measures of SES, or SNPs in the genes most associated with renal disease (IRF5 [rs4728142], BLK [rs2736340], STAT4 [rs3024912], and HLA-DRB10301 and DRB11501) did not substantively alter this relationship. Conclusion. European ancestry is protective against the development of renal disease in SLE, an effect that is independent of other genetic ancestries, candidate risk alleles, and socioeconomic factors.",
author = "Richman, {Ilana B.} and Taylor, {Kimberly E.} and Chung, {Sharon A.} and Laura Trupin and Michelle Petri and Edward Yelin and Graham, {Robert R.} and Annette Lee and Behrens, {Timothy W.} and Gregersen, {Peter K.} and Seldin, {Michael F} and Criswell, {Lindsey A.}",
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T1 - European genetic ancestry is associated with a decreased risk of lupus nephritis

AU - Richman, Ilana B.

AU - Taylor, Kimberly E.

AU - Chung, Sharon A.

AU - Trupin, Laura

AU - Petri, Michelle

AU - Yelin, Edward

AU - Graham, Robert R.

AU - Lee, Annette

AU - Behrens, Timothy W.

AU - Gregersen, Peter K.

AU - Seldin, Michael F

AU - Criswell, Lindsey A.

PY - 2012/10

Y1 - 2012/10

N2 - Objective. African Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than are SLE patients of European descent. This study was undertaken to investigate whether European genetic ancestry protects against the development of lupus nephritis, with the aim of exploring the genetic and socioeconomic factors that might explain this effect. Methods. This was a cross-sectional study of SLE patients from a multiethnic case collection. Participants were genotyped for 126 single-nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. Logistic regression was used to test the association between European ancestry and renal disease. Analyses were adjusted for continental ancestries, socioeconomic status (SES), and candidate genes. Results. Participants (n = 1,906) had, on average, 62.4% European, 15.8% African, 11.5% East Asian, 6.5% Amerindian, and 3.8% South Asian ancestry. Among the participants, 656 (34%) had renal disease. A 10% increase in the proportion of European ancestry estimated in each participant was associated with a 15% reduction in the odds of having renal disease, after adjustment for disease duration and sex (odds ratio 0.85, 95% confidence interval 0.82-0.87; P = 1.9 × 10-30). Adjustment for other genetic ancestries, measures of SES, or SNPs in the genes most associated with renal disease (IRF5 [rs4728142], BLK [rs2736340], STAT4 [rs3024912], and HLA-DRB10301 and DRB11501) did not substantively alter this relationship. Conclusion. European ancestry is protective against the development of renal disease in SLE, an effect that is independent of other genetic ancestries, candidate risk alleles, and socioeconomic factors.

AB - Objective. African Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than are SLE patients of European descent. This study was undertaken to investigate whether European genetic ancestry protects against the development of lupus nephritis, with the aim of exploring the genetic and socioeconomic factors that might explain this effect. Methods. This was a cross-sectional study of SLE patients from a multiethnic case collection. Participants were genotyped for 126 single-nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. Logistic regression was used to test the association between European ancestry and renal disease. Analyses were adjusted for continental ancestries, socioeconomic status (SES), and candidate genes. Results. Participants (n = 1,906) had, on average, 62.4% European, 15.8% African, 11.5% East Asian, 6.5% Amerindian, and 3.8% South Asian ancestry. Among the participants, 656 (34%) had renal disease. A 10% increase in the proportion of European ancestry estimated in each participant was associated with a 15% reduction in the odds of having renal disease, after adjustment for disease duration and sex (odds ratio 0.85, 95% confidence interval 0.82-0.87; P = 1.9 × 10-30). Adjustment for other genetic ancestries, measures of SES, or SNPs in the genes most associated with renal disease (IRF5 [rs4728142], BLK [rs2736340], STAT4 [rs3024912], and HLA-DRB10301 and DRB11501) did not substantively alter this relationship. Conclusion. European ancestry is protective against the development of renal disease in SLE, an effect that is independent of other genetic ancestries, candidate risk alleles, and socioeconomic factors.

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