AUTHOR=Elghzaly Ashraf A. , Sun Celi , Looger Loren L. , Hirose Misa , Salama Mohamed , Khalil Noha M. , Behiry Mervat Essam , Hegazy Mohamed Tharwat , Hussein Mohamed Ahmed , Salem Mohamad Nabil , Eltoraby Ehab , Tawhid Ziyad , Alwasefy Mona , Allam Walaa , El-Shiekh Iman , Elserafy Menattallah , Abdelnaser Anwar , Hashish Sara , Shebl Nourhan , Shahba Abeer Abdelmonem , Elgirby Amira , Hassab Amina , Refay Khalida , El-Touchy Hanan Mohamed , Youssef Ali , Shabacy Fatma , Hashim Abdelkader Ahmed , Abdelzaher Asmaa , Alshebini Emad , Fayez Dalia , El-Bakry Samah A. , Elzohri Mona H. , Abdelsalam Eman Nagiub , El-Khamisy Sherif F. , Ibrahim Saleh , Ragab Gaafar , Nath Swapan K. TITLE=Genome-wide association study for systemic lupus erythematosus in an egyptian population JOURNAL=Frontiers in Genetics VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.948505 DOI=10.3389/fgene.2022.948505 ISSN=1664-8021 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.