Title
Transancestral mapping and genetic load in systemic lupus erythematosus
Date Issued
17 July 2017
Access level
open access
Resource Type
journal article
Author(s)
Langefeld C.D.
Ainsworth H.C.
Graham D.S.C.
Kelly J.A.
Comeau M.E.
Marion M.C.
Howard T.D.
Ramos P.S.
Croker J.A.
Morris D.L.
Sandling J.K.
Almlöf J.C.
Babini A.M.
Baca V.
Bengtsson A.A.
Berbotto G.A.
Bijl M.
Brown E.E.
Brunner H.I.
Cardiel M.H.
Catoggio L.
Cervera R.
Dahlqvist S.R.
D'Alfonso S.
Da Silva B.M.
De La RúaFigueroa I.
Doria A.
Edberg J.C.
Endreffy E.
Esquivel-Valerio J.A.
Fortin P.R.
Freedman B.I.
Frostegård J.
Garcýá M.A.
De La Torre I.G.
Gilkeson G.S.
Gladman D.D.
Gunnarsson I.
Guthridge J.M.
Huggins J.L.
James J.A.
Kallenberg C.G.M.
Kamen D.L.
Karp D.R.
Kaufman K.M.
Kottyan L.C.
Kovács L.
Laustrup H.
Lauwerys B.R.
Li Q.Z.
Maradiaga-Ceceną M.A.
Martín J.
McCune J.M.
McWilliams D.R.
Merrill J.T.
Miranda P.
Moctezuma J.F.
Nath S.K.
Niewold T.B.
Orozco L.
Ortego-Centeno N.
Petri M.
Pineau C.A.
Pons-Estel B.A.
Pope J.
Raj P.
Ramsey-Goldman R.
Reveille J.D.
Russell L.P.
Sabio J.M.
Aguilar-Salinas C.A.
Scherbarth H.R.
Scorza R.
Seldin M.F.
Sjöwall C.
Svenungsson E.
Thompson S.D.
Toloza S.M.A.
Truedsson L.
Tusié-Luna T.
Vasconcelos C.
Vilá L.M.
Wallace D.J.
Weisman M.H.
Wither J.E.
Bhangale T.
Oksenberg J.R.
Rioux J.D.
Gregersen P.K.
Syvänen A.C.
Rönnblom L.
Criswell L.A.
Jacob C.O.
Sivils K.L.
Tsao B.P.
Schanberg L.E.
Behrens T.W.
UAB School of Medicine
Publisher(s)
Springer Nature
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.
Volume
8
Language
English
OCDE Knowledge area
Genética, Herencia
Reumatología
Scopus EID
2-s2.0-85024906085
PubMed ID
Source
Nature Communications
ISSN of the container
20411723
Sponsor(s)
National Institute of General Medical Sciences P30GM110766
Sources of information:
Directorio de Producción Científica
Scopus