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- Title
Genome-wide association study for systemic lupus erythematosus in an egyptian population.
- Authors
Elghzaly, Ashraf A.; Celi Sun; 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
- Abstract
Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across transancestral 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.
- Subjects
EGYPT; GENOME-wide association studies; SYSTEMIC lupus erythematosus; EGYPTIANS; GENETIC variation; GENE expression
- Publication
Frontiers in Genetics, 2022, Vol 13, p1
- ISSN
1664-8021
- Publication type
Article
- DOI
10.3389/fgene.2022.948505