Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/123026
Title: Transancestral mapping and genetic load in systemic lupus erythematosus
Author: 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 S.
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.
Keywords: Lupus eritematós
Malalties autoimmunitàries
Genètica humana
Estudi de casos
Lupus erythematosus
Autoimmune diseases
Human genetics
Case studies
Issue Date: 17-Jul-2017
Publisher: Nature Publishing Group
Abstract: 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 for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
Note: Reproducció del document publicat a: https://doi.org/10.1038/ncomms16021
It is part of: Nature Communications, 2017, vol. 8, p. 16021
URI: http://hdl.handle.net/2445/123026
Related resource: https://doi.org/10.1038/ncomms16021
ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (Medicina)

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