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Transancestral mapping and genetic load in systemic lupus erythematosus
Wake Forest School Med, NC 27101 USA; Wake Forest School Med, NC 27101 USA.
Wake Forest School Med, NC 27101 USA; Wake Forest School Med, NC 27101 USA.
Kings Coll London, England.
Oklahoma Medical Research Fdn, OK 73104 USA.
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2017 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 16021Article in journal (Refereed) Published
Abstract [en]

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 (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P amp;lt; 5 x 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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2017. Vol. 8, article id 16021
National Category
Medical Genetics
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URN: urn:nbn:se:liu:diva-139555DOI: 10.1038/ncomms16021ISI: 000405680100001PubMedID: 28714469OAI: oai:DiVA.org:liu-139555DiVA, id: diva2:1130125
Note

Funding Agencies|Alliance for Lupus Research; Arthritis Research UK Special Strategic Award [19289]; George Koukis; National Institute for Health Research (NIHR) Biomedical Research Centre based at Guys and St Thomas NHS Foundation Trust; Kings College London; NIH [AR049084]; International Consortium on the Genetics of Systemic Lupus Erythematosus (SLEGEN) [AI083194, CA141700, AR058621]; Proyecto de Excelencia; Consejeria de Andalucia; MUSC [UL1RR029882, 5P60AR062755]; US National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) [K01 AR067280, P60 AR062755, N01AR22265]; APPLE Investigators; NIAMS/NIH [P50-AR055503]; RILITE foundation; Genentech; [AR043814]; [AR-065626]; [AR060366]; [MD007909]; [AI107176]; [AR-057172]; [RC2 AR058959]; [U19 A1082714]; [R01 AR063124]; [P30 GM110766]; [R01 AR056360]; [P60 AR053308]; [R01AR43727]; [NIH AR 043727]; [069572]

Available from: 2017-08-08 Created: 2017-08-08 Last updated: 2018-01-13

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