Richa Saxena1, Robert M Plenge2, Andrew C Bjonnes1, Hassan S Dashti1, Yukinori Okada3, Wessam Gad El Haq4, Mohammed Hammoudeh5, Samar Al Emadi5, Basel K Masri6, Hussein Halabi7, Humeira Badsha8, Imad W Uthman9, Lauren Margolin10, Namrata Gupta10, Ziyad R Mahfoud4, Marianthi Kapiri4, Soha R Dargham4, Grace Aranki4, Layla A Kazkaz11, Thurayya Arayssi4. 1. Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, and Broad Institute, Cambridge, Massachusetts. 2. Broad Institute, Cambridge, Massachusetts, and Merck Research Laboratories and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 3. Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan, and Riken, Yokohama, Japan. 4. Weill Cornell Medicine-Qatar, Education City, Doha, Qatar. 5. Hamad Medical Corporation, Doha, Qatar. 6. Jordan Hospital, Amman, Jordan. 7. King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia. 8. Dr. Humeira Badsha Medical Center, Dubai, United Arab Emirates. 9. American University of Beirut, Beirut, Lebanon. 10. Broad Institute, Cambridge, Massachusetts. 11. Tishreen Hospital, Damascus, Syria.
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.
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.
Authors: Philippa M Wells; Frances M K Williams; M L Matey-Hernandez; Cristina Menni; Claire J Steves Journal: J Autoimmun Date: 2019-03-05 Impact factor: 7.094
Authors: Soha R Dargham; Sumeja Zahirovic; Mohammed Hammoudeh; Samar Al Emadi; Basel K Masri; Hussein Halabi; Humeira Badsha; Imad Uthman; Ziyad R Mahfoud; Hadil Ashour; Wissam Gad El Haq; Karim Bayoumy; Marianthi Kapiri; Richa Saxena; Robert M Plenge; Layla Kazkaz; Thurayya Arayssi Journal: PLoS One Date: 2018-12-19 Impact factor: 3.240
Authors: Julian Ramírez-Bello; José M Fragoso; Isidro Alemán-Ávila; Silvia Jiménez-Morales; Alma D Campos-Parra; Rosa Elda Barbosa-Cobos; José Moreno Journal: Front Genet Date: 2020-02-20 Impact factor: 4.599