Frontiers in Genetics (Oct 2022)
Genome-wide association study for systemic lupus erythematosus in an egyptian population
- Ashraf A. Elghzaly,
- Celi Sun,
- Loren L. Looger,
- Misa Hirose,
- Mohamed Salama,
- Noha M. Khalil,
- Mervat Essam Behiry,
- Mohamed Tharwat Hegazy,
- Mohamed Ahmed Hussein,
- Mohamad Nabil Salem,
- Ehab Eltoraby,
- Ziyad Tawhid,
- Mona Alwasefy,
- Walaa Allam,
- Iman El-Shiekh,
- Menattallah Elserafy,
- Anwar Abdelnaser,
- Sara Hashish,
- Nourhan Shebl,
- Abeer Abdelmonem Shahba,
- Amira Elgirby,
- Amina Hassab,
- Khalida Refay,
- Hanan Mohamed El-Touchy,
- Ali Youssef,
- Fatma Shabacy,
- Abdelkader Ahmed Hashim,
- Asmaa Abdelzaher,
- Emad Alshebini,
- Dalia Fayez,
- Samah A. El-Bakry,
- Mona H. Elzohri,
- Eman Nagiub Abdelsalam,
- Sherif F. El-Khamisy,
- Sherif F. El-Khamisy,
- Sherif F. El-Khamisy,
- Saleh Ibrahim,
- Gaafar Ragab,
- Swapan K. Nath
Affiliations
- Ashraf A. Elghzaly
- Department of Clinical Pathology, Faculty of Medicine, Mansoura University, El-Mansoura, Egypt
- Celi Sun
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States
- Loren L. Looger
- Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, San Diego, CA, United States
- Misa Hirose
- Division of Genetics, Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
- Mohamed Salama
- Institute of Global Health and Human Ecology, The American University in Cairo, New Cairo, Egypt
- Noha M. Khalil
- Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
- Mervat Essam Behiry
- Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
- Mohamed Tharwat Hegazy
- Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
- Mohamed Ahmed Hussein
- Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
- Mohamad Nabil Salem
- Department of Internal Medicine, Faculty of Medicine, Beni-Suef University, Beni Suef, Egypt
- Ehab Eltoraby
- Department of Internal Medicine, Faculty of Medicine, Mansoura University, El-Mansoura, Egypt
- Ziyad Tawhid
- Department of Clinical Pathology, Faculty of Medicine, Mansoura University, El-Mansoura, Egypt
- Mona Alwasefy
- Department of Clinical Pathology, Faculty of Medicine, Mansoura University, El-Mansoura, Egypt
- Walaa Allam
- Center for Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt
- Iman El-Shiekh
- Center for Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt
- Menattallah Elserafy
- Center for Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt
- Anwar Abdelnaser
- Institute of Global Health and Human Ecology, The American University in Cairo, New Cairo, Egypt
- Sara Hashish
- Institute of Global Health and Human Ecology, The American University in Cairo, New Cairo, Egypt
- Nourhan Shebl
- Institute of Global Health and Human Ecology, The American University in Cairo, New Cairo, Egypt
- Abeer Abdelmonem Shahba
- 0Department of Internal Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
- Amira Elgirby
- 1Department of Internal Medicine, Faculty of Medicine, Alexandria University, Bab Sharqi, Egypt
- Amina Hassab
- 2Department of Clinical Pathology, Faculty of Medicine, Alexandria University, Bab Sharqi, Egypt
- Khalida Refay
- 3Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
- Hanan Mohamed El-Touchy
- 3Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
- Ali Youssef
- 4Department of Rheumatology and Immunology, Faculty of Medicine, Benha University Hospital, Benha, Egypt
- Fatma Shabacy
- 4Department of Rheumatology and Immunology, Faculty of Medicine, Benha University Hospital, Benha, Egypt
- Abdelkader Ahmed Hashim
- 5Department of Internal Medicine, Faculty of Medicine, South Valley University, Qena, Egypt
- Asmaa Abdelzaher
- 6Department of Clinical Pathology, Faculty of Medicine, South Valley University, Qena, Egypt
- Emad Alshebini
- 7Department of Internal Medicine, Faculty of Medicine, Menoufia University, Al Minufiyah, Egypt
- Dalia Fayez
- 8Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Samah A. El-Bakry
- 8Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Mona H. Elzohri
- 9Department of Internal Medicine, Faculty of Medicine, Assiut University, Asyut, Egypt
- Eman Nagiub Abdelsalam
- 0Department of Clinical Pathology, Faculty of Medicine, Assiut University, Asyut, Egypt
- Sherif F. El-Khamisy
- 1The Healthy Lifespan Institute, University of Sheffield, Sheffield, United Kingdom
- Sherif F. El-Khamisy
- 2The Institute of Cancer Therapeutics, University of Bradford, Bradford, United Kingdom
- Sherif F. El-Khamisy
- Center for Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt
- Saleh Ibrahim
- Division of Genetics, Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
- Gaafar Ragab
- Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
- Swapan K. Nath
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States
- DOI
- https://doi.org/10.3389/fgene.2022.948505
- Journal volume & issue
-
Vol. 13
Abstract
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 = 109). We identified a novel genome-wide significant locus near IRS1/miR-5702 (Pcorrected = 1.98 × 10−8) and eight novel suggestive loci (Pcorrected < 1.0 × 10−5). We also replicated (Pperm < 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 (r2 > 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.
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