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. 2010 Dec;62(12):3722-9.
doi: 10.1002/art.27753.

Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus

Elena Sanchez  1 , Ryan D Webb, Astrid Rasmussen, Jennifer A Kelly, Laura Riba, Kenneth M Kaufman, Ignacio Garcia-de la Torre, Jose F Moctezuma, Marco A Maradiaga-Ceceña, Mario H Cardiel-Rios, Eduardo Acevedo, Mariano Cucho-Venegas, Mercedes A Garcia, Susana Gamron, Bernardo A Pons-Estel, Carlos Vasconcelos, Javier Martin, Teresa Tusié-Luna, John B Harley, Bruce Richardson, Amr H Sawalha, Marta E Alarcón-Riquelme
Affiliations

Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus

Elena Sanchez et al. Arthritis Rheum. 2010 Dec.

Abstract

Objective: To assess whether genetically determined Amerindian ancestry predicts increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus (SLE).

Methods: Single-nucleotide polymorphisms (SNPs) within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation between ancestry and the presence of risk alleles was analyzed using linear regression.

Results: A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, ITGAM, and IRF5 were associated with lupus in a Hispanic Mestizo cohort enriched for European and Amerindian ancestry. In addition, 2 SNPs within the major histocompatibility complex region, previously shown to be associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression, we predicted an average increase of 2.34 risk alleles when comparing an SLE patient with 100% Amerindian ancestry versus an SLE patient with 0% Amerindian ancestry (P < 0.0001). SLE patients with 43% more Amerindian ancestry were predicted to carry 1 additional risk allele.

Conclusion: Our results demonstrate that Amerindian ancestry is associated with an increased number of risk alleles for SLE.

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Figures

Figure 1
Figure 1
Scatter plot of the input data overlaid with the fitted regression line, 95% confidence limits, and 95% prediction limits. The 95% confidence limits in the plot are point-wise limits that cover the mean number of risk alleles for a particular proportion of Amerindian ancestry with probability 0.95. The 95% prediction limits illustrate the point-wise limits for a future measurement of risk alleles for a given proportion of Amerindian ancestry with probability 0.95.
See this image and copyright information in PMC

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