Transancestral mapping and genetic load in systemic lupus erythematosus

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...

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Detalles Bibliográficos
Autores: 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.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/123026
Acceso en línea:https://hdl.handle.net/2445/123026
Access Level:acceso abierto
Palabra clave:Lupus eritematós
Malalties autoimmunitàries
Genètica humana
Estudi de casos
Lupus erythematosus
Autoimmune diseases
Human genetics
Case studies
Descripción
Sumario: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.

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