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

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Institute of Global Health & Human Ecology

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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, Saleh Ibrahim , Gaafar Ragab , Swapan K Nath

Document Type

Research Article

Publication Title

Frontiers in Genetics

Publication Date

Fall 10-17-2022




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 (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.

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