A Multinational Arab Genome-Wide Association Study Identifies New Genetic Associations for Rheumatoid Arthritis

Richa Saxena, Robert M. Plenge, Andrew C. Bjonnes, Hassan S. Dashti, Yukinori Okada, Wessam Gad El Haq, Mohammed Hammoudeh, Samar Al Emadi, Basel K. Masri, Hussein Halabi, Humeira Badsha, Imad W. Uthman, Lauren Margolin, Namrata Gupta, Ziyad R. Mahfoud, Marianthi Kapiri, Soha R. Dargham, Grace Aranki, Layla A. Kazkaz, Thurayya Arayssi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)976-985
Number of pages10
JournalArthritis and Rheumatology
Volume69
Issue number5
DOIs
Publication statusPublished - 1 May 2017
Externally publishedYes

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Genome-Wide Association Study
Rheumatoid Arthritis
Population
Single Nucleotide Polymorphism
Qatar
United Arab Emirates
Lebanon
Jordan
Intergenic DNA
Genetic Loci
Saudi Arabia

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

A Multinational Arab Genome-Wide Association Study Identifies New Genetic Associations for Rheumatoid Arthritis. / Saxena, Richa; Plenge, Robert M.; Bjonnes, Andrew C.; Dashti, Hassan S.; Okada, Yukinori; Gad El Haq, Wessam; Hammoudeh, Mohammed; Al Emadi, Samar; Masri, Basel K.; Halabi, Hussein; Badsha, Humeira; Uthman, Imad W.; Margolin, Lauren; Gupta, Namrata; Mahfoud, Ziyad R.; Kapiri, Marianthi; Dargham, Soha R.; Aranki, Grace; Kazkaz, Layla A.; Arayssi, Thurayya.

In: Arthritis and Rheumatology, Vol. 69, No. 5, 01.05.2017, p. 976-985.

Research output: Contribution to journalArticle

Saxena, R, Plenge, RM, Bjonnes, AC, Dashti, HS, Okada, Y, Gad El Haq, W, Hammoudeh, M, Al Emadi, S, Masri, BK, Halabi, H, Badsha, H, Uthman, IW, Margolin, L, Gupta, N, Mahfoud, ZR, Kapiri, M, Dargham, SR, Aranki, G, Kazkaz, LA & Arayssi, T 2017, 'A Multinational Arab Genome-Wide Association Study Identifies New Genetic Associations for Rheumatoid Arthritis', Arthritis and Rheumatology, vol. 69, no. 5, pp. 976-985. https://doi.org/10.1002/art.40051
Saxena, Richa ; Plenge, Robert M. ; Bjonnes, Andrew C. ; Dashti, Hassan S. ; Okada, Yukinori ; Gad El Haq, Wessam ; Hammoudeh, Mohammed ; Al Emadi, Samar ; Masri, Basel K. ; Halabi, Hussein ; Badsha, Humeira ; Uthman, Imad W. ; Margolin, Lauren ; Gupta, Namrata ; Mahfoud, Ziyad R. ; Kapiri, Marianthi ; Dargham, Soha R. ; Aranki, Grace ; Kazkaz, Layla A. ; Arayssi, Thurayya. / A Multinational Arab Genome-Wide Association Study Identifies New Genetic Associations for Rheumatoid Arthritis. In: Arthritis and Rheumatology. 2017 ; Vol. 69, No. 5. pp. 976-985.
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abstract = "Objective: 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. Methods: 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. Results: 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. Conclusion: 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.",
author = "Richa Saxena and Plenge, {Robert M.} and Bjonnes, {Andrew C.} and Dashti, {Hassan S.} and Yukinori Okada and {Gad El Haq}, Wessam and Mohammed Hammoudeh and {Al Emadi}, Samar and Masri, {Basel K.} and Hussein Halabi and Humeira Badsha and Uthman, {Imad W.} and Lauren Margolin and Namrata Gupta and Mahfoud, {Ziyad R.} and Marianthi Kapiri and Dargham, {Soha R.} and Grace Aranki and Kazkaz, {Layla A.} and Thurayya Arayssi",
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T1 - A Multinational Arab Genome-Wide Association Study Identifies New Genetic Associations for Rheumatoid Arthritis

AU - Saxena, Richa

AU - Plenge, Robert M.

AU - Bjonnes, Andrew C.

AU - Dashti, Hassan S.

AU - Okada, Yukinori

AU - Gad El Haq, Wessam

AU - Hammoudeh, Mohammed

AU - Al Emadi, Samar

AU - Masri, Basel K.

AU - Halabi, Hussein

AU - Badsha, Humeira

AU - Uthman, Imad W.

AU - Margolin, Lauren

AU - Gupta, Namrata

AU - Mahfoud, Ziyad R.

AU - Kapiri, Marianthi

AU - Dargham, Soha R.

AU - Aranki, Grace

AU - Kazkaz, Layla A.

AU - Arayssi, Thurayya

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N2 - Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

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