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Transancestral mapping and genetic load in systemic lupus erythematosus.

Publication ,  Journal Article
Langefeld, CD; Ainsworth, HC; Cunninghame Graham, DS; Kelly, JA; Comeau, ME; Marion, MC; Howard, TD; Ramos, PS; Croker, JA; Morris, DL; Baca, V ...
Published in: Nat Commun
July 17, 2017
Published version (DOI) Link to item

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.

Duke Scholars

Laura Eve Schanberg
Author Laura Eve Schanberg Pediatrics, Rheumatology
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Published In

Nat Commun

DOI

10.1038/ncomms16021

EISSN

2041-1723

Publication Date

July 17, 2017

Volume

8

Start / End Page

16021

Location

England

Related Subject Headings

  • White People
  • Sequence Deletion
  • Polymorphism, Single Nucleotide
  • Mutagenesis, Insertional
  • Multifactorial Inheritance
  • Lupus Erythematosus, Systemic
  • Logistic Models
  • Humans
  • Hispanic or Latino
  • HLA Antigens
 

Citation

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Chicago
ICMJE
MLA
NLM
Langefeld, C. D., Ainsworth, H. C., Cunninghame Graham, D. S., Kelly, J. A., Comeau, M. E., Marion, M. C., … Vyse, T. J. (2017). Transancestral mapping and genetic load in systemic lupus erythematosus. Nat Commun, 8, 16021. https://doi.org/10.1038/ncomms16021
Langefeld, Carl D., Hannah C. Ainsworth, Deborah S. Cunninghame Graham, Jennifer A. Kelly, Mary E. Comeau, Miranda C. Marion, Timothy D. Howard, et al. “Transancestral mapping and genetic load in systemic lupus erythematosus.” Nat Commun 8 (July 17, 2017): 16021. https://doi.org/10.1038/ncomms16021.
Langefeld CD, Ainsworth HC, Cunninghame Graham DS, Kelly JA, Comeau ME, Marion MC, et al. Transancestral mapping and genetic load in systemic lupus erythematosus. Nat Commun. 2017 Jul 17;8:16021.
Langefeld, Carl D., et al. “Transancestral mapping and genetic load in systemic lupus erythematosus.” Nat Commun, vol. 8, July 2017, p. 16021. Pubmed, doi:10.1038/ncomms16021.
Langefeld CD, Ainsworth HC, Cunninghame Graham DS, Kelly JA, Comeau ME, Marion MC, Howard TD, Ramos PS, Croker JA, Morris DL, Sandling JK, Almlöf JC, Acevedo-Vásquez EM, Alarcón GS, Babini AM, Baca V, Bengtsson AA, Berbotto GA, Bijl M, Brown EE, Brunner HI, Cardiel MH, Catoggio L, Cervera R, Cucho-Venegas JM, Dahlqvist SR, D’Alfonso S, Da Silva BM, de la Rúa Figueroa I, Doria A, Edberg JC, Endreffy E, Esquivel-Valerio JA, Fortin PR, Freedman BI, Frostegård J, García MA, de la Torre IG, Gilkeson GS, Gladman DD, Gunnarsson I, Guthridge JM, Huggins JL, James JA, Kallenberg CGM, Kamen DL, Karp DR, Kaufman KM, Kottyan LC, Kovács L, Laustrup H, Lauwerys BR, Li Q-Z, Maradiaga-Ceceña MA, Martín J, McCune JM, McWilliams DR, Merrill JT, Miranda P, Moctezuma JF, Nath SK, Niewold TB, Orozco L, Ortego-Centeno N, Petri M, Pineau CA, Pons-Estel BA, Pope J, Raj P, Ramsey-Goldman R, Reveille JD, Russell LP, Sabio JM, Aguilar-Salinas CA, Scherbarth HR, Scorza R, Seldin MF, Sjöwall C, Svenungsson E, Thompson SD, Toloza SMA, Truedsson L, Tusié-Luna T, Vasconcelos C, Vilá LM, Wallace DJ, Weisman MH, Wither JE, Bhangale T, Oksenberg JR, Rioux JD, Gregersen PK, Syvänen A-C, Rönnblom L, Criswell LA, Jacob CO, Sivils KL, Tsao BP, Schanberg LE, Behrens TW, Silverman ED, Alarcón-Riquelme ME, Kimberly RP, Harley JB, Wakeland EK, Graham RR, Gaffney PM, Vyse TJ. Transancestral mapping and genetic load in systemic lupus erythematosus. Nat Commun. 2017 Jul 17;8:16021.

Published In

Nat Commun

DOI

10.1038/ncomms16021

EISSN

2041-1723

Publication Date

July 17, 2017

Volume

8

Start / End Page

16021

Location

England

Related Subject Headings

  • White People
  • Sequence Deletion
  • Polymorphism, Single Nucleotide
  • Mutagenesis, Insertional
  • Multifactorial Inheritance
  • Lupus Erythematosus, Systemic
  • Logistic Models
  • Humans
  • Hispanic or Latino
  • HLA Antigens