Transancestral mapping and genetic load in systemic lupus erythematosus
- Langefeld, Carl D.
- Ainsworth, Hannah C.
- Graham, Deborah S. Cunninghame
- Kelly, Jennifer A.
- Comeau, Mary E.
- Marion, Miranda C.
- Howard, Timothy D.
- Ramos, Paula S.
- Croker, Jennifer A.
- Morris, David L.
- Sandling, Johanna K.
- Almlöf, Jonas Carlsson
- Acevedo-Vásquez, Eduardo M.
- Alarcón, Graciela
- Babini, Alejandra M.
- Baca, Vicente
- Bengtsson, Anders A.
- Berbotto, Guillermo A.
- Bijl, Marc
- Brown, Elizabeth E.
- Brunner, Hermine I.
- Cardiel, Mario H.
- Catoggio, Luis
- Cervera i Segura, Ricard, 1960-
- Cucho-Venegas, Jorge M.
- Dahlqvist, Solbritt Rantapää
- D'Alfonso, Sandra
- Da Silva, Berta Martins
- de la Rúa Figueroa, Iñigo
- Doria, Andrea
- Edberg, Jeffrey C.
- Endreffy, Emóke
- Esquivel-Valerio, Jorge A.
- Fortin, Paul R.
- Freedman, Barry I.
- Frostegård, Johan
- García, Mercedes A.
- de la Torre, Ignacio García
- Gilkeson, Gary S.
- Gladman, Dafna D.
DOIAbstract
Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10-8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis fo...
Add to ORKG