title: Rheumatoid arthritis in Latin Americans enriched for Amerindian ancestry is associated with loci in chromosomes 1, 12, and 13, and the HLA class II region.
abstract: OBJECTIVE
  To identify susceptibility loci for rheumatoid arthritis (RA) in Latin American individuals with admixed European and Amerindian genetic ancestry.
  
  
  METHODS
  Genotyping was performed in 1,475 patients with RA and 1,213 control subjects, using a customized BeadArray containing 196,524 markers covering loci previously associated with various autoimmune diseases. Principal components analysis (EigenSoft package) and Structure software were used to identify outliers and define the population substructure. REAP software was used to define cryptic relatedness and duplicates, and genetic association analyses were conducted using Plink statistical software.
  
  
  RESULTS
  A strong genetic association between RA and the major histocompatibility complex region was observed, localized within BTNL2/DRA-DQB1- DQA2 (P = 7.6 × 10(-10) ), with 3 independent effects. We identified an association in the PLCH2-HES5-TNFRSF14-MMEL1 region of chromosome 1 (P = 9.77 × 10(-6) ), which was previously reported in Europeans, Asians, and Native Canadians. We identified one novel putative association in ENOX1 on chromosome 13 (P = 3.24 × 10(-7) ). Previously reported associations were observed in the current study, including PTPN22, SPRED2, STAT4, IRF5, CCL21, and IL2RA, although the significance was relatively moderate. Adjustment for Amerindian ancestry improved the association of a novel locus in chromosome 12 at C12orf30 (NAA25) (P = 3.9 × 10(-6) ). Associations with the HLA region, SPRED2, and PTPN22 improved in individuals positive for anti-cyclic citrullinated peptide antibodies.
  
  
  CONCLUSIONS
  Our data define, for the first time, the contribution of Amerindian ancestry to the genetic architecture of RA in an admixed Latin American population by confirming the role of the HLA region and supporting the association with a locus in chromosome 1. In addition, we provide data for novel putative loci in chromosomes 12 and 13.
authors: Centro Pfizer-Universidad de Granada-Junta de Andalucía de Genómica e Investigaciones Oncológicas, Granada, Spain.
authors: David
authors: D
authors: López Herráez
authors: Manuel
authors: M
authors: Martínez-Bueno
authors: Laura
authors: L
authors: Riba
authors: Ignacio
authors: I
authors: García de la Torre
authors: Mónica
authors: M
authors: Sacnún
authors: Mario
authors: M
authors: Goñi
authors: Guillermo A
authors: GA
authors: Berbotto
authors: Sergio
authors: S
authors: Paira
authors: Jorge Luis
authors: JL
authors: Musuruana
authors: César E
authors: CE
authors: Graf
authors: Alejandro J
authors: AJ
authors: Alvarellos
authors: Osvaldo D
authors: OD
authors: Messina
authors: Alejandra M
authors: AM
authors: Babini
authors: Ingrid
authors: I
authors: Strusberg
authors: Juan Carlos
authors: JC
authors: Marcos
authors: Hugo
authors: H
authors: Scherbarth
authors: Alberto J
authors: AJ
authors: Spindler
authors: Ana
authors: A
authors: Quinteros
authors: Sergio M A
authors: SM
authors: Toloza
authors: José Luis C
authors: JL
authors: Moreno
authors: Luis J
authors: LJ
authors: Catoggio
authors: Guillermo
authors: G
authors: Tate
authors: Alicia
authors: A
authors: Eimon
authors: Gustavo
authors: G
authors: Citera
authors: Antonio
authors: A
authors: Catalán Pellet
authors: Gustavo G
authors: GG
authors: Nasswetter
authors: Mario H
authors: MH
authors: Cardiel
authors: Pedro
authors: P
authors: Miranda
authors: Francisco
authors: F
authors: Ballesteros
authors: Jorge A
authors: JA
authors: Esquivel-Valerio
authors: Marco A
authors: MA
authors: Maradiaga-Ceceña
authors: Eduardo M
authors: EM
authors: Acevedo-Vásquez
authors: Conrado
authors: C
authors: García García
authors: Bernardo A
authors: BA
authors: Pons-Estel
authors: Marta E
authors: ME
authors: Alarcón-Riquelme
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007199:Indians, South American; D007843:Latin America; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D006680:HLA Antigens