Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian–European populations

Abstract

Objective Amerindian-Europeans, Asians and African-Americans have an excess morbidity from SLE and higher prevalence of lupus nephritis than Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and socio-demographic characteristics and clinical features in a large cohort of Amerindian-European SLE patients. Methods A total of 2116 SLE patients of Amerindian-European origin and 4001 SLE patients of European descent with clinical data were used in the study. Genotyping of 253 continental ancestry informative markers was performed on the Illumina platform. The STRUCTURE and ADMIXTURE software were used to determine genetic ancestry of each individual. Correlation between ancestry and socio-demographic and clinical data were analyzed using logistic regression. Results The average Amerindian genetic ancestry of 2116 SLE patients was 40.7%. There was an increased risk of having renal involvement (P<0.0001, OR= 3.50 95%CI 2.63-4.63) and an early age of onset with the presence of Amerindian genetic ancestry (P<0.0001). Amerindian ancestry protected against photosensitivity (P<0.0001, OR= 0.58 95%CI 0.44-0.76), oral ulcers (P<0.0001, OR= 0.55 95%CI 0.42-0.72), and serositis (P<0.0001, OR= 0.56 95%CI 0.41-0.75) after adjustment by age, gender and age of onset. However, gender and age of onset had stronger effects on malar rash, discoid rash, arthritis and neurological involvement than genetic ancestry. Conclusion In general, genetic Amerindian ancestry correlates with lower socio-demographic status and increases the risk for developing renal involvement and SLE at an earlier age of onset.

Widely divergent transcriptional patterns between SLE patients of different ancestral backgrounds in sorted immune cell populations

“…AA ancestral background has been associated with increased incidence and severity of disease, and increased levels of autoantibodies and type I IFN [1][13, 39, 43]. In the present study, we saw a greater number of DEGs in AA patients as compared to EA patients in each cell type.…”

“…Clinically, SLE patients from different ancestral backgrounds manifest differently. For example, Amerindian genetic ancestry is associated with earlier onset of SLE and an increased risk of developing renal involvement as compared to European-American ancestry [1]. Distinct patterns of genetic association with SLE exist between world populations, with some genetic factors being associated in one background but not the other [2-6].…”

Multisystemic diseases and ethnicity: a focus on lupus erythematosus, systemic sclerosis, sarcoidosis and Behçet disease

“…For example, Sanchez et al found more mouth ulcers, malar rashes, serositis, arthritis, neurological impairment and discoid lupus erythematosus (DLE) in patients of European descent compared with American-Indians; however, these are weak correlations which often disappear with multivariate analysis. 3 In a large multiethnic cohort of SLE, DLE, arthritis and terminal renal failure were negatively associated with Hispanic, but positively associated with African-American populations. 6 Another study demonstrated a positive association of antiphospholipid antibodies in 'Aboriginal' Canadians with SLE, compared with persons of Asian or European descent.…”

“…The recent use of genetic tools such as ancestry informative markers now enables a more objective assessment of ethnicity, even in persons of mixed ancestral backgrounds. 3 Studies have also demonstrated that the prognosis of SLE is worse in nonwhite persons, in whom there is a younger age at onset of their disease, as well as a higher frequency of severe renal disease. [1][2][3][4][5] These observations may be due to 'protective factors' associated with European ancestry or may indicate the presence of specific risk factors associated with other ethnic groups.…”

Genetics of human lupus nephritis

“…The incidence and prevalence of SLE is higher in non-European ancestry, especially in African ancestry. The severity of SLE also varies among the ethnic groups, being more severe in non-European populations [2–4]. Supporting a genetic contribution to disease, monozygotic twins are much more likely to be concordant for SLE than dizygotic twins (concordance rate 24% and 2%, respectively) [5].…”