Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity - Citation formats | Research Explorer (2022)

  • Authors:
  • Steve Eyre
  • John Bowes
  • Jane Worthington
  • And 15 others
  • External authors:
  • Buhm Han
  • Dorothée Diogo
  • Henrik Kallberg
  • Alexandra Zhernakova
  • Leonid Padyukov
  • Yukinori Okada
  • Miguel A. González-Gay
  • Solbritt Rantapää-Dahlqvist
  • Javier Martin
  • Tom W J Huizinga
  • Robert M. Plenge
  • Peter K. Gregersen
  • Lars Klareskog
  • Paul I W De Bakker
  • Soumya Raychaudhuri
  • Overview
  • Citation formats

Standard

Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity. / Han, Buhm; Diogo, Dorothée; Eyre, Steve; Kallberg, Henrik; Zhernakova, Alexandra; Bowes, John; Padyukov, Leonid; Okada, Yukinori; González-Gay, Miguel A.; Rantapää-Dahlqvist, Solbritt; Martin, Javier; Huizinga, Tom W J; Plenge, Robert M.; Worthington, Jane; Gregersen, Peter K.; Klareskog, Lars; De Bakker, Paul I W; Raychaudhuri, Soumya.

In: American Journal of Human Genetics, Vol. 94, No. 4, 03.04.2014, p. 522-532.

Research output: Contribution to journalArticlepeer-review

Harvard

Han, B, Diogo, D, Eyre, S, Kallberg, H, Zhernakova, A, Bowes, J, Padyukov, L, Okada, Y, González-Gay, MA, Rantapää-Dahlqvist, S, Martin, J, Huizinga, TWJ, Plenge, RM, Worthington, J, Gregersen, PK, Klareskog, L, De Bakker, PIW & Raychaudhuri, S 2014, 'Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity', American Journal of Human Genetics, vol. 94, no. 4, pp. 522-532. https://doi.org/10.1016/j.ajhg.2014.02.013

APA

Han, B., Diogo, D., Eyre, S., Kallberg, H., Zhernakova, A., Bowes, J., Padyukov, L., Okada, Y., González-Gay, M. A., Rantapää-Dahlqvist, S., Martin, J., Huizinga, T. W. J., Plenge, R. M., Worthington, J., Gregersen, P. K., Klareskog, L., De Bakker, P. I. W., & Raychaudhuri, S. (2014). Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity. American Journal of Human Genetics, 94(4), 522-532. https://doi.org/10.1016/j.ajhg.2014.02.013

Vancouver

Han B, Diogo D, Eyre S, Kallberg H, Zhernakova A, Bowes J et al. Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity. American Journal of Human Genetics. 2014 Apr 3;94(4):522-532. https://doi.org/10.1016/j.ajhg.2014.02.013

Author

Han, Buhm ; Diogo, Dorothée ; Eyre, Steve ; Kallberg, Henrik ; Zhernakova, Alexandra ; Bowes, John ; Padyukov, Leonid ; Okada, Yukinori ; González-Gay, Miguel A. ; Rantapää-Dahlqvist, Solbritt ; Martin, Javier ; Huizinga, Tom W J ; Plenge, Robert M. ; Worthington, Jane ; Gregersen, Peter K. ; Klareskog, Lars ; De Bakker, Paul I W ; Raychaudhuri, Soumya. / Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity. In: American Journal of Human Genetics. 2014 ; Vol. 94, No. 4. pp. 522-532.

Bibtex

@article{950c3e9c9f4b44d6a3efdaca8c586d19,

title = "Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity",

abstract = "Despite progress in defining human leukocyte antigen (HLA) alleles for anti-citrullinated-protein-autoantibody-positive (ACPA+) rheumatoid arthritis (RA), identifying HLA alleles for ACPA-negative (ACPA-) RA has been challenging because of clinical heterogeneity within clinical cohorts. We imputed 8,961 classical HLA alleles, amino acids, and SNPs from Immunochip data in a discovery set of 2,406 ACPA- RA case and 13,930 control individuals. We developed a statistical approach to identify and adjust for clinical heterogeneity within ACPA- RA and observed independent associations for serine and leucine at position 11 in HLA-DRβ1 (p = 1.4 × 10-13, odds ratio [OR] = 1.30) and for aspartate at position 9 in HLA-B (p = 2.7 × 10-12, OR = 1.39) within the peptide binding grooves. These amino acid positions induced associations at HLA-DRB1{\^a}̂ -03 (encoding serine at 11) and HLA-B {\^a}̂ -08 (encoding aspartate at 9). We validated these findings in an independent set of 427 ACPA- case subjects, carefully phenotyped with a highly sensitive ACPA assay, and 1,691 control subjects (HLA-DRβ1 Ser11+Leu11: p = 5.8 × 10-4, OR = 1.28; HLA-B Asp9: p = 2.6 × 10-3, OR = 1.34). Although both amino acid sites drove risk of ACPA+ and ACPA- disease, the effects of individual residues at HLA-DRβ1 position 11 were distinct (p <2.9 × 10-107). We also identified an association with ACPA + RA at HLA-A position 77 (p = 2.7 × 10-8, OR = 0.85) in 7,279 ACPA+ RA case and 15,870 control subjects. These results contribute to mounting evidence that ACPA+ and ACPA - RA are genetically distinct and potentially have separate autoantigens contributing to pathogenesis. We expect that our approach might have broad applications in analyzing clinical conditions with heterogeneity at both major histocompatibility complex (MHC) and non-MHC regions. {\textcopyright} 2014 The American Society of Human Genetics.",

author = "Buhm Han and Doroth{\'e}e Diogo and Steve Eyre and Henrik Kallberg and Alexandra Zhernakova and John Bowes and Leonid Padyukov and Yukinori Okada and Gonz{\'a}lez-Gay, {Miguel A.} and Solbritt Rantap{\"a}{\"a}-Dahlqvist and Javier Martin and Huizinga, {Tom W J} and Plenge, {Robert M.} and Jane Worthington and Gregersen, {Peter K.} and Lars Klareskog and {De Bakker}, {Paul I W} and Soumya Raychaudhuri",

note = "U01 GM092691, NIGMS NIH HHS, United States",

year = "2014",

month = apr,

day = "3",

doi = "10.1016/j.ajhg.2014.02.013",

language = "English",

volume = "94",

pages = "522--532",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "4",

}

RIS

TY - JOUR

T1 - Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity

AU - Han, Buhm

AU - Diogo, Dorothée

AU - Eyre, Steve

AU - Kallberg, Henrik

AU - Zhernakova, Alexandra

AU - Bowes, John

AU - Padyukov, Leonid

AU - Okada, Yukinori

AU - González-Gay, Miguel A.

AU - Rantapää-Dahlqvist, Solbritt

AU - Martin, Javier

AU - Huizinga, Tom W J

AU - Plenge, Robert M.

AU - Worthington, Jane

AU - Gregersen, Peter K.

AU - Klareskog, Lars

AU - De Bakker, Paul I W

AU - Raychaudhuri, Soumya

N1 - U01 GM092691, NIGMS NIH HHS, United States

PY - 2014/4/3

Y1 - 2014/4/3

N2 - Despite progress in defining human leukocyte antigen (HLA) alleles for anti-citrullinated-protein-autoantibody-positive (ACPA+) rheumatoid arthritis (RA), identifying HLA alleles for ACPA-negative (ACPA-) RA has been challenging because of clinical heterogeneity within clinical cohorts. We imputed 8,961 classical HLA alleles, amino acids, and SNPs from Immunochip data in a discovery set of 2,406 ACPA- RA case and 13,930 control individuals. We developed a statistical approach to identify and adjust for clinical heterogeneity within ACPA- RA and observed independent associations for serine and leucine at position 11 in HLA-DRβ1 (p = 1.4 × 10-13, odds ratio [OR] = 1.30) and for aspartate at position 9 in HLA-B (p = 2.7 × 10-12, OR = 1.39) within the peptide binding grooves. These amino acid positions induced associations at HLA-DRB1â̂ -03 (encoding serine at 11) and HLA-B â̂ -08 (encoding aspartate at 9). We validated these findings in an independent set of 427 ACPA- case subjects, carefully phenotyped with a highly sensitive ACPA assay, and 1,691 control subjects (HLA-DRβ1 Ser11+Leu11: p = 5.8 × 10-4, OR = 1.28; HLA-B Asp9: p = 2.6 × 10-3, OR = 1.34). Although both amino acid sites drove risk of ACPA+ and ACPA- disease, the effects of individual residues at HLA-DRβ1 position 11 were distinct (p <2.9 × 10-107). We also identified an association with ACPA + RA at HLA-A position 77 (p = 2.7 × 10-8, OR = 0.85) in 7,279 ACPA+ RA case and 15,870 control subjects. These results contribute to mounting evidence that ACPA+ and ACPA - RA are genetically distinct and potentially have separate autoantigens contributing to pathogenesis. We expect that our approach might have broad applications in analyzing clinical conditions with heterogeneity at both major histocompatibility complex (MHC) and non-MHC regions. © 2014 The American Society of Human Genetics.

AB - Despite progress in defining human leukocyte antigen (HLA) alleles for anti-citrullinated-protein-autoantibody-positive (ACPA+) rheumatoid arthritis (RA), identifying HLA alleles for ACPA-negative (ACPA-) RA has been challenging because of clinical heterogeneity within clinical cohorts. We imputed 8,961 classical HLA alleles, amino acids, and SNPs from Immunochip data in a discovery set of 2,406 ACPA- RA case and 13,930 control individuals. We developed a statistical approach to identify and adjust for clinical heterogeneity within ACPA- RA and observed independent associations for serine and leucine at position 11 in HLA-DRβ1 (p = 1.4 × 10-13, odds ratio [OR] = 1.30) and for aspartate at position 9 in HLA-B (p = 2.7 × 10-12, OR = 1.39) within the peptide binding grooves. These amino acid positions induced associations at HLA-DRB1â̂ -03 (encoding serine at 11) and HLA-B â̂ -08 (encoding aspartate at 9). We validated these findings in an independent set of 427 ACPA- case subjects, carefully phenotyped with a highly sensitive ACPA assay, and 1,691 control subjects (HLA-DRβ1 Ser11+Leu11: p = 5.8 × 10-4, OR = 1.28; HLA-B Asp9: p = 2.6 × 10-3, OR = 1.34). Although both amino acid sites drove risk of ACPA+ and ACPA- disease, the effects of individual residues at HLA-DRβ1 position 11 were distinct (p <2.9 × 10-107). We also identified an association with ACPA + RA at HLA-A position 77 (p = 2.7 × 10-8, OR = 0.85) in 7,279 ACPA+ RA case and 15,870 control subjects. These results contribute to mounting evidence that ACPA+ and ACPA - RA are genetically distinct and potentially have separate autoantigens contributing to pathogenesis. We expect that our approach might have broad applications in analyzing clinical conditions with heterogeneity at both major histocompatibility complex (MHC) and non-MHC regions. © 2014 The American Society of Human Genetics.

U2 - 10.1016/j.ajhg.2014.02.013

DO - 10.1016/j.ajhg.2014.02.013

M3 - Article

C2 - 24656864

VL - 94

SP - 522

EP - 532

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 4

ER -

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