TY - JOUR
T1 - Genome-wide association study for systemic lupus erythematosus in an egyptian population
AU - Elghzaly, Ashraf A.
AU - Sun, Celi
AU - Looger, Loren L.
AU - Hirose, Misa
AU - Salama, Mohamed
AU - Khalil, Noha M.
AU - Behiry, Mervat Essam
AU - Hegazy, Mohamed Tharwat
AU - Hussein, Mohamed Ahmed
AU - Salem, Mohamad Nabil
AU - Eltoraby, Ehab
AU - Tawhid, Ziyad
AU - Alwasefy, Mona
AU - Allam, Walaa
AU - El-Shiekh, Iman
AU - Elserafy, Menattallah
AU - Abdelnaser, Anwar
AU - Hashish, Sara
AU - Shebl, Nourhan
AU - Shahba, Abeer Abdelmonem
AU - Elgirby, Amira
AU - Hassab, Amina
AU - Refay, Khalida
AU - El-Touchy, Hanan Mohamed
AU - Youssef, Ali
AU - Shabacy, Fatma
AU - Hashim, Abdelkader Ahmed
AU - Abdelzaher, Asmaa
AU - Alshebini, Emad
AU - Fayez, Dalia
AU - El-Bakry, Samah A.
AU - Elzohri, Mona H.
AU - Abdelsalam, Eman Nagiub
AU - El-Khamisy, Sherif F.
AU - Ibrahim, Saleh
AU - Ragab, Gaafar
AU - Nath, Swapan K.
N1 - Funding Information:
This research was funded by the University of Lübeck and by the National Institutes of Health, grant numbers MD007909 and AR060366.
Publisher Copyright:
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.
PY - 2022/10/17
Y1 - 2022/10/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85141000577&partnerID=8YFLogxK
U2 - 10.3389/fgene.2022.948505
DO - 10.3389/fgene.2022.948505
M3 - Journal articles
AN - SCOPUS:85141000577
SN - 1664-8021
VL - 13
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 948505
ER -