Genome-wide association study for systemic lupus erythematosus in an egyptian population.

Autor: Elghzaly AA; Department of Clinical Pathology, Faculty of Medicine, Mansoura University, El-Mansoura, Egypt., Sun C; Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States., Looger LL; Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, San Diego, CA, United States., Hirose M; Division of Genetics, Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany., Salama M; Institute of Global Health and Human Ecology, The American University in Cairo, New Cairo, Egypt., Khalil NM; Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt., Behiry ME; Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt., Hegazy MT; Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt., Hussein MA; Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt., Salem MN; Department of Internal Medicine, Faculty of Medicine, Beni-Suef University, Beni Suef, Egypt., Eltoraby E; Department of Internal Medicine, Faculty of Medicine, Mansoura University, El-Mansoura, Egypt., Tawhid Z; Department of Clinical Pathology, Faculty of Medicine, Mansoura University, El-Mansoura, Egypt., Alwasefy M; Department of Clinical Pathology, Faculty of Medicine, Mansoura University, El-Mansoura, Egypt., Allam W; Center for Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt., El-Shiekh I; Center for Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt., Elserafy M; Center for Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt., Abdelnaser A; Institute of Global Health and Human Ecology, The American University in Cairo, New Cairo, Egypt., Hashish S; Institute of Global Health and Human Ecology, The American University in Cairo, New Cairo, Egypt., Shebl N; Institute of Global Health and Human Ecology, The American University in Cairo, New Cairo, Egypt., Shahba AA; Department of Internal Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt., Elgirby A; Department of Internal Medicine, Faculty of Medicine, Alexandria University, Bab Sharqi, Egypt., Hassab A; Department of Clinical Pathology, Faculty of Medicine, Alexandria University, Bab Sharqi, Egypt., Refay K; Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt., El-Touchy HM; Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt., Youssef A; Department of Rheumatology and Immunology, Faculty of Medicine, Benha University Hospital, Benha, Egypt., Shabacy F; Department of Rheumatology and Immunology, Faculty of Medicine, Benha University Hospital, Benha, Egypt., Hashim AA; Department of Internal Medicine, Faculty of Medicine, South Valley University, Qena, Egypt., Abdelzaher A; Department of Clinical Pathology, Faculty of Medicine, South Valley University, Qena, Egypt., Alshebini E; Department of Internal Medicine, Faculty of Medicine, Menoufia University, Al Minufiyah, Egypt., Fayez D; Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt., El-Bakry SA; Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Elzohri MH; Department of Internal Medicine, Faculty of Medicine, Assiut University, Asyut, Egypt., Abdelsalam EN; Department of Clinical Pathology, Faculty of Medicine, Assiut University, Asyut, Egypt., El-Khamisy SF; The Healthy Lifespan Institute, University of Sheffield, Sheffield, United Kingdom.; The Institute of Cancer Therapeutics, University of Bradford, Bradford, United Kingdom.; Center for Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt., Ibrahim S; Division of Genetics, Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany., Ragab G; Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt., Nath SK; Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States.
Jazyk: angličtina
Zdroj: Frontiers in genetics [Front Genet] 2022 Oct 17; Vol. 13, pp. 948505. Date of Electronic Publication: 2022 Oct 17 (Print Publication: 2022).
DOI: 10.3389/fgene.2022.948505
Abstrakt: Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians-an admixed North African/Middle Eastern population-using 537 patients and 883 controls. To identify novel susceptibility loci and replicate previously known loci, we performed imputation-based association analysis with 6,382,276 SNPs while accounting for individual admixture. We validated the association analysis using adaptive permutation tests ( n = 10 9 ). We identified a novel genome-wide significant locus near IRS1/miR-5702 (P corrected = 1.98 × 10 -8 ) and eight novel suggestive loci (P corrected < 1.0 × 10 -5 ). We also replicated (P perm < 0.01) 97 previously known loci with at least one associated nearby SNP, with ITGAM, DEF6-PPARD and IRF5 the top three replicated loci. SNPs correlated ( r 2 > 0.8) with lead SNPs from four suggestive loci ( ARMC9, DIAPH3 , IFLDT1, and ENTPD3 ) were associated with differential gene expression (3.5 × 10 -95 < p < 1.0 × 10 -2 ) across diverse tissues. These loci are involved in cellular proliferation and invasion-pathways prominent in lupus and nephritis. Our study highlights the utility of GWAS in an admixed Egyptian population for delineating new genetic associations and for understanding SLE pathogenesis.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Elghzaly, Sun, Looger, Hirose, Salama, Khalil, Behiry, Hegazy, Hussein, Salem, Eltoraby, Tawhid, Alwasefy, Allam, El-Shiekh, Elserafy, Abdelnaser, Hashish, Shebl, Shahba, Elgirby, Hassab, Refay, El-Touchy, Youssef, Shabacy, Hashim, Abdelzaher, Alshebini, Fayez, El-Bakry, Elzohri, Abdelsalam, El-Khamisy, Ibrahim, Ragab and Nath.)
Databáze: MEDLINE
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