Association analysis in a Latin American population revealed ethnic differences in rheumatoid arthritis-associated SNPs in Caucasian and Asian populations

Large genome-wide association studies (GWAS) have increased our knowledge of the genetic risk factors of rheumatoid arthritis (RA). However, little is known about genetic susceptibility in populations with a large admixture of Amerindian ancestry. The aim of the present study was to test the general...

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Bibliographic Details
Published in:Scientific reports 2020-05, Vol.10 (1), p.7879, Article 7879
Main Authors: Castro-Santos, P, Verdugo, R A, Alonso-Arias, R, Gutiérrez, M A, Suazo, J, Aguillón, J C, Olloquequi, J, Pinochet, C, Lucia, A, Quiñones, L A, Díaz-Peña, R
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Arthritis, Rheumatoid - ethnology
Arthritis, Rheumatoid - genetics
Asian Continental Ancestry Group - genetics
Association analysis
Cell activation
Cohort Studies
European Continental Ancestry Group - genetics
Female
Gene Frequency
Gene mapping
Genetic Association Studies - methods
Genetic Association Studies - statistics & numerical data
Genetic Predisposition to Disease - ethnology
Genetic Predisposition to Disease - genetics
Genome-wide association studies
Genome-Wide Association Study - methods
Genome-Wide Association Study - statistics & numerical data
Genotype
Genotyping
Haplotypes
Humans
Latin America
Lymphocytes T
Male
Middle Aged
Polymerase chain reaction
Polymorphism, Single Nucleotide
Population genetics
Population studies
Rheumatoid arthritis
Risk factors
Single-nucleotide polymorphism
Stat4 protein
Transcription
Young Adult
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Summary:Large genome-wide association studies (GWAS) have increased our knowledge of the genetic risk factors of rheumatoid arthritis (RA). However, little is known about genetic susceptibility in populations with a large admixture of Amerindian ancestry. The aim of the present study was to test the generalizability of previously reported RA loci in a Latin American (LA) population with admixed ancestry. We selected 128 single nucleotide polymorphisms (SNPs) in linkage equilibrium, with high association to RA in multiple populations of non-Amerindian origin. Genotyping of 118 SNPs was performed in 313 RA patients/487 healthy control subjects by mid-density arrays of polymerase chain reaction (PCR). Some of the identified associations were validated in an additional cohort (250 cases/290 controls). One marker, the SNP rs2451258, located upstream of T Cell Activation RhoGTPase Activating Protein (TAGAP) gene, showed significant association with RA (p = 5 × 10 ), whereas 18 markers exhibited suggestive associations (p 
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-64659-0