You are here

Article Text

Article menu

Download PDFPDF

Epidemiology & Outcomes
701 A million veteran program (MVP) genome-wide association study (GWAS) of systemic and cutaneous lupus erythematosus (SLE & CLE)
  1. Dennis H Clark1,
  2. Isaac TW Harley2,
  3. Celi Sun3,
  4. Iouri Chepelev1,4,
  5. R Hal Scofield3,5,
  6. Kenneth M Kaufman1,6,7,
  7. John B Harley1,4 and
  8. Viktoryia Laurynenka1,6
  1. 1US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA
  2. 2US Department of Veterans Affairs Medical Center, Denver, Colorado, USA
  3. 3US Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA
  4. 4Cincinnati Education and Research for Veterans Foundation (CERVF), Cincinnati, Ohio USA
  5. 5Oklahoma Medical Research Foundation (OMRF) and Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
  6. 6Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
  7. 7Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

Abstract

Background >36,000 Veterans have been diagnosed with systemic lupus erythematosus (SLE). With the SLE and cutaneous lupus (CLE) cases and unaffected controls in MVP, we performed a genome-wide association study (GWAS).

Methods Cases with two SLE (phe_695_42) or CLE (phe_695_41) (S/CLE) qualifying diagnoses were compared to controls with none of 44 idiopathic inflammatory, autoimmune, and laboratory concept codes. We used OHDSI Atas and Gen3 GWAS. The 104 and 11 published non-Hispanic white (European (EU) and black (admixed African (AA)) SLE risk loci were queried in the MVP at - log_pc>3.3 and -log_pc>2.3, respectively.

Results MVP S/CLE has 2,629 cases, containing 1,575 males, 1,054 females with 1,396 EU and 982 AA; 489,637 controls qualify.

GWAS for 1,396 EU Veterans with S/CLE compared to 352,354 controls has χ2 inflation of 1.041. Of 6,419 genetic markers in 7 loci at -log_p>7.3, HLA has 6,310 (98.3%) with C4B being most associated at -log_p=24.4. Also, IRF5 (Ch-7), -log p=12.6; ITGAM (Ch-16), -log_p=11.9; NCF2 (Ch- 1), -log_p=10.1; STAT4 (third intron) (Ch-2), -log_p=10.1; TNFAIP3 (Ch-6), -log_p=7.4; and IKZF1 (Ch-7), -log_p=7.3 (figure 1).

The GWAS for the 982 AA MVP Veterans in S/CLE compared to 91,062 controls has 1.029 inflation. With HLA-DQA1, -log_p=14.6; ITGAM (Ch-16), -log_p=14.5; and POTEA (Ch-8), -log_p=8.1. POTEA has 12 variants exceeding -log_p>7.3, representing a probable convincing locus (figure 1).

Of the 106 EU and 11 AA SLE risk loci now known at -log_p>7.3, at least, 26 of 106 (25%) at - log_p>3.3 and 5 of 11 (45%) at -log_p>2.3 are in the EU SLE and 19 of 106 and 5 of 11 in AA SLE are found in these MVP data.

Conclusion While the MVP GWAS of S/CLE in MVP reproduces many known SLE risk loci in EU and AA, findings also highlight genetic divergence between these ancestries, such as the differences in and near ITGAM and the novel AA locus at POTEA.

Abstract 701 Figure 1
Abstract 701 Figure 1

Comparative MVPGW/l5 Analysis of Lupus (SLE or CLE) for the non-Hispanic Black andnon-Hispanic White VeteransGWASof non-Hispanic Slack lupuscases(n=982) vs controls• {n=91,062} on left, withGWASof non-Hispanic lupus cases(n=1396) vs controls• (n=3S2,3S4}on right.• Controls exduded 44 conce-pu for autoimmune or immune mediated conditions, as wellaspositive relevant tab results.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/lupus-2023-lupus21century.52

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.