title: A Multinational Arab Genome-Wide Association Study Identifies New Genetic Associations for Rheumatoid Arthritis.
abstract: Genetic factors underlying susceptibility to rheumatoid arthritis (RA) in Arab populations are largely unknown. This genome-wide association study (GWAS) was undertaken to explore the generalizability of previously reported RA loci to Arab subjects and to discover new Arab-specific genetic loci.
  
  
  
  The Genetics of Rheumatoid Arthritis in Some Arab States Study was designed to examine the genetics and clinical features of RA patients from Jordan, the Kingdom of Saudi Arabia, Lebanon, Qatar, and the United Arab Emirates. In total, >7 million single-nucleotide polymorphisms (SNPs) were tested for association with RA overall and with seropositive or seronegative RA in 511 RA cases and 352 healthy controls. In addition, replication of 15 signals was attempted in 283 RA cases and 221 healthy controls. A genetic risk score of 68 known RA SNPs was also examined in this study population.
  
  
  
  Three loci (HLA region, intergenic 5q13, and 17p13 at SMTNL2/GGT6) reached genome-wide significance in the analyses of association with RA and with seropositive RA, and for all 3 loci, evidence of independent replication was demonstrated. Consistent with the findings in European and East Asian populations, the association of RA with HLA-DRB1 amino acid position 11 conferred the strongest effect (P = 4.8 × 10-16), and a weighted genetic risk score of previously associated RA loci was found to be associated with RA (P = 3.41 × 10-5) and with seropositive RA (P = 1.48 × 10-6) in this population. In addition, 2 novel associations specific to Arab populations were found at the 5q13 and 17p13 loci.
  
  
  
  This first RA GWAS in Arab populations confirms that established HLA-region and known RA risk alleles contribute strongly to the risk and severity of disease in some Arab groups, suggesting that the genetic architecture of RA is similar across ethnic groups. Moreover, this study identified 2 novel RA risk loci in Arabs, offering further population-specific insights into the pathophysiology of RA.
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, and Broad Institute, Cambridge, Massachusetts.
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
authors.affiliation: Broad Institute, Cambridge, Massachusetts, and Merck Research Laboratories and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Plenge
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, and Broad Institute, Cambridge, Massachusetts.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Bjonnes
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, and Broad Institute, Cambridge, Massachusetts.
authors.forename: Hassan S
authors.initials: HS
authors.lastname: Dashti
authors.affiliation: Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan, and Riken, Yokohama, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Weill Cornell Medicine-Qatar, Education City, Doha, Qatar.
authors.forename: Wessam
authors.initials: W
authors.lastname: Gad El Haq
authors.affiliation: Hamad Medical Corporation, Doha, Qatar.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Hammoudeh
authors.affiliation: Hamad Medical Corporation, Doha, Qatar.
authors.forename: Samar
authors.initials: S
authors.lastname: Al Emadi
authors.affiliation: Jordan Hospital, Amman, Jordan.
authors.forename: Basel K
authors.initials: BK
authors.lastname: Masri
authors.affiliation: King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia.
authors.forename: Hussein
authors.initials: H
authors.lastname: Halabi
authors.affiliation: Dr. Humeira Badsha Medical Center, Dubai, United Arab Emirates.
authors.forename: Humeira
authors.initials: H
authors.lastname: Badsha
authors.affiliation: American University of Beirut, Beirut, Lebanon.
authors.forename: Imad W
authors.initials: IW
authors.lastname: Uthman
authors.affiliation: Broad Institute, Cambridge, Massachusetts.
authors.forename: Lauren
authors.initials: L
authors.lastname: Margolin
authors.affiliation: Broad Institute, Cambridge, Massachusetts.
authors.forename: Namrata
authors.initials: N
authors.lastname: Gupta
authors.affiliation: Weill Cornell Medicine-Qatar, Education City, Doha, Qatar.
authors.forename: Ziyad R
authors.initials: ZR
authors.lastname: Mahfoud
authors.affiliation: Weill Cornell Medicine-Qatar, Education City, Doha, Qatar.
authors.forename: Marianthi
authors.initials: M
authors.lastname: Kapiri
authors.affiliation: Weill Cornell Medicine-Qatar, Education City, Doha, Qatar.
authors.forename: Soha R
authors.initials: SR
authors.lastname: Dargham
authors.affiliation: Weill Cornell Medicine-Qatar, Education City, Doha, Qatar.
authors.forename: Grace
authors.initials: G
authors.lastname: Aranki
authors.affiliation: Tishreen Hospital, Damascus, Syria.
authors.forename: Layla A
authors.initials: LA
authors.lastname: Kazkaz
authors.affiliation: Weill Cornell Medicine-Qatar, Education City, Doha, Qatar.
authors.forename: Thurayya
authors.initials: T
authors.lastname: Arayssi
mesh_terms: D000328:Adult; D018912:Arabs / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D021901:DNA, Intergenic / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D007597:Jordan; D007861:Lebanon; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011780:Qatar; D012217:Rheumatoid Factor / Q000276:immunology; D012529:Saudi Arabia; D014479:United Arab Emirates; D005723:gamma-Glutamyltransferase / Q000235:genetics*
chemical_list: D021901:DNA, Intergenic; D006680:HLA Antigens; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; D010750:Phosphoproteins; C000593215:SMTNL2 protein, human; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor; D005723:gamma-Glutamyltransferase; C554782:gamma-glutamyltransferase, human