Amerindian ancestry in Argentina is associated with increased risk for systemic lupus erythematosus

Seldin, Michael F.; Qi, Lihong; Scherbarth, Hugo R.; Tian, Chao; Ransom, Michael R.; Silva, Gonçalo; Belmont, John W.; Gamron, Susana; Allievi, Alberto; Palatnik, Simon A.; Saurit, Verónica; Paira, Sergio; Graf, César; Guillerón, Carolina; Catoggio, Luís J.; Prigione, Cristina; Berbotto, Guillermo; García, Mercedes; Perandones, Carlos E.; Truedsson, Lennart; Abderrahim, Hadi; Battagliotti, Cristina; Pons-Estel, Bernardo A.; Alarcón‐Riquelme, Marta E.

doi:10.1038/gene.2008.25

Cited by 29 publications

(21 citation statements)

References 25 publications

(24 reference statements)

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“…More recently, in mixed population groups such as in the United States, ancestry informative markers (AIMs) or sufficient numbers of unselected independent markers (low intermarker LD) have been used to examine ancestry relationships between and within continents as well as admixture and autoimmune disease. Evidence for increased frequency of SLE has been associated with both West African ancestry and Native American ancestry [103-105]. Several studies of SLE have used this approach to examine whether endophenotypes of this disease are more likely to be associated with particular ancestry [106-109].…”

Section: Ancestry Makes a Differencementioning

confidence: 99%

The genetics of human autoimmune disease: A perspective on progress in the field and future directions

Seldin

2015

Journal of Autoimmunity

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Progress in defining the genetics of autoimmune disease has been dramatically enhanced by large scale genetic studies. Genome-wide approaches examining hundreds or for some diseases thousands of cases and controls have been implemented using high throughput genotyping and appropriate algorithms to provide a wealth of data over the last decade. These studies have identified hundreds of non-HLA loci as well as further defining HLA region variations that predispose to different autoimmune diseases. These studies to identify genetic risk loci are also complemented by progress in gene expression studies including definition of expression quantitative trait loci (eQTL), various alterations in chromatin structure including histone marks, DNase I sensitivity, repressed chromatin regions as well as transcript factor binding sites. Integration of this information can partially explain why particular variations can alter proclivity to autoimmune phenotypes. Despite our incomplete knowledge base with only partial definition of hereditary factors and possible functional connections, this progress has and will continue to facilitate a better understanding of critical pathways and critical changes in immunoregulation. Advances in defining and understanding functional variants potentially can lead to both novel therapeutics and personalized medicine in which therapeutic approaches are chosen based on particular molecular phenotypes and genomic alterations.

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Section: Ancestry Makes a Differencementioning

confidence: 99%

The genetics of human autoimmune disease: A perspective on progress in the field and future directions

Seldin

2015

Journal of Autoimmunity

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“…At a genome-wide level, geographically and culturally isolated populations develop genetic variation over time that is unique to that particular population, and this population-specific genetic variation may be associated with, or causative of, important phenotypes such as disease risk and xenobiotic response (Seldin et al 2008; Fejerman et al 2008). For this reason, genetic admixture may be an important component of individual variability in many traits.…”

Section: Introductionmentioning

confidence: 99%

Indigenous American Ancestry is Associated with Arsenic Methylation Efficiency in an Admixed Population of Northwest Mexico

Gomez‐Rubio

Klimentidis

Cantú-Soto

et al. 2011

Journal of Toxicology and Environmental Health, Part A

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Many studies provide evidence relating lower human arsenic (As) methylation efficiency, represented by high % urinary monomethylarsonic acid (MMA(V)), with several arsenic-induced diseases, possibly due to the fact that MMA(V) serves as a proxy for MMA(III), the most toxic arsenic metabolite. Some epidemiological studies have suggested that indigenous Americans (AME) methylate As more efficiently, however data supporting this have been equivocal. The aim of this study was to characterize the association between AME ancestry and arsenic methylation efficiency using a panel of ancestry informative genetic markers to determine individual ancestry proportions in an admixed population (composed of two or more isolated ancestral populations) of 746 individuals environmentally exposed to arsenic in northwest Mexico. Total urinary As (TAs) mean and range were 170.4 and 2.3–1053.5 μg/L, while %AME mean and range were 72.4 and 23–100. Adjusted (gender, age, AS3MT 7388/M287T haplotypes, body mass index (BMI), and TAs) multiple regression model showed that higher AME ancestry is associated with lower %uMMA excretion in this population (p <0.01). The data also showed a significant interaction between BMI and gender indicating negative association between BMI and %uMMA, stronger in women than men (p <0.01). Moreover age and the AS3MT variants 7388 (intronic) and M287T (non-synonymous) were also significantly associated with As methylation efficiency (p = 0.01). This study highlights the importance of BMI and indigenous American ancestry in some of the observed variability in As methylation efficiency, underscoring the need to be considered in epidemiology studies, particularly those carried out in admixed populations.

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“…2-4 Recent studies, particularly in Latino populations, have examined genetic admixture in relation to SLE severity, and have shown a trend toward more severe disease with increasing Amerindian ancestry or decreasing European ancestry. 5, 6 …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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Previous work has demonstrated that northern and southern European ancestries are associated with specific systemic lupus erythematosus (SLE) manifestations. Here, 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 to northern European ancestry, southern European ancestry was associated with autoantibody production (OR=1.40, 95% 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.

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Amerindian ancestry in Argentina is associated with increased risk for systemic lupus erythematosus

Cited by 29 publications

References 25 publications

The genetics of human autoimmune disease: A perspective on progress in the field and future directions

The genetics of human autoimmune disease: A perspective on progress in the field and future directions

Indigenous American Ancestry is Associated with Arsenic Methylation Efficiency in an Admixed Population of Northwest Mexico

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

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