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Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis
Open accessAbstract
The genetic association of the major histocompatibility complex (MHC) to rheumatoid arthritis risk has commonly been attributed to alleles in HLA-DRB1. However, debate persists about the identity of the causal variants in HLA-DRB1 and the presence of independent effects elsewhere in the MHC. Using existing genome-wide SNP data in 5,018 individuals with seropositive rheumatoid arthritis (cases) and 14,974 unaffected controls, we imputed and tested classical alleles and amino acid polymorphisms in HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1 and HLA-DRB1, as well as 3,117 SNPs across the MHC. Conditional and haplotype analyses identified that three amino acid positions (11, 71 and 74) in HLA-DRβ1 and single–amino-acid polymorphisms in HLA-B (at position 9) and HLA-DPβ1 (at position 9), which are all located in peptide-binding grooves, almost completely explain the MHC association to rheumatoid arthritis risk. This study shows how imputation of functional variation from large reference panels can help fine map association signals in the MHC.
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Cites
Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248
Self-citationBrowning, B. L., & Browning, S. R. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.01.005 · Cited by 1,640
de Bakker, P. I. W., McVean, G., Sabeti, P. C., Miretti, M. M., Green, T., Marchini, J., Ke, X., Monsuur, A. J., Whittaker, P., Delgado, M., et al. (2006) · Nature Genetics · doi:10.1038/ng1885 · Cited by 766
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Schizophrenia risk from complex variation of complement component 4
Sekar, A., Bialas, A. R., de Rivera, H., Davis, A., Hammond, T. R., Kamitaki, N., Tooley, K., Presumey, J., Baum, M., Van Doren, V., et al. (2016) · Nature · doi:10.1038/nature16549 · Cited by 2,394
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the RACI consortium, Okada, Y., the GARNET consortium, Wu, D., Trynka, G., Raj, T., Terao, C., Ikari, K., Kochi, Y., Ohmura, K., et al. (2014) · Nature · doi:10.1038/nature12873 · Cited by 2,310
Self-citationGenome-wide association studies
Uffelmann, E., Huang, Q. Q., Munung, N. S., de Vries, J., Okada, Y., Martin, A. R., Martin, H. C., Lappalainen, T., & Posthuma, D. (2021) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00056-9 · Cited by 1,849
Zhang, X., Zhang, D., Jia, H., Feng, Q., Wang, D., Liang, D., Wu, X., Li, J., Tang, L., Li, Y., et al. (2015) · Nature Medicine · doi:10.1038/nm.3914 · Cited by 1,690
Immunopathogenesis of Rheumatoid Arthritis
Firestein, G. S., & McInnes, I. B. (2017) · Immunity · doi:10.1016/j.immuni.2017.02.006 · Cited by 1,301
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Chen, J., Wright, K., Davis, J. M., Jeraldo, P., Marietta, E. V., Murray, J., Nelson, H., Matteson, E. L., & Taneja, V. (2016) · Genome Medicine · doi:10.1186/s13073-016-0299-7 · Cited by 858
Oral microbiomes: more and more importance in oral cavity and whole body
Gao, L., Xu, T., Huang, G., Jiang, S., Gu, Y., & Chen, F. (2018) · Protein & Cell · doi:10.1007/s13238-018-0548-1 · Cited by 770
High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis
Syndicate, B. I. R. A. G. A. G. S., Eyre, S., Wellcome Trust Case Control Consortium, Bowes, J., Diogo, D., Lee, A., Barton, A., Martin, P., Zhernakova, A., Stahl, E., et al. (2012) · Nature Genetics · doi:10.1038/ng.2462 · Cited by 653
Self-citationThe MHC locus and genetic susceptibility to autoimmune and infectious diseases
Matzaraki, V., Kumar, V., Wijmenga, C., & Zhernakova, A. (2017) · Genome biology · doi:10.1186/s13059-017-1207-1 · Cited by 566
Scally, S. W., Petersen, J., Law, S. C., Dudek, N. L., Nel, H. J., Loh, K. L., Wijeyewickrema, L. C., Eckle, S. B. G., van Heemst, J., Pike, R. N., et al. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20131241 · Cited by 429
The UK-PSCSC Consortium, Liu, J. Z., The International IBD Genetics Consortium, The International PSC Study Group, Hov, J. R., Folseraas, T., Ellinghaus, E., Rushbrook, S. M., Doncheva, N. T., Andreassen, O. A., et al. (2013) · Nature Genetics · doi:10.1038/ng.2616 · Cited by 391
Self-citationPatsopoulos, N. A., Barcellos, L. F., Hintzen, R. Q., Schaefer, C., van Duijn, C. M., Noble, J. A., Raj, T., IMSGC, ANZgene, Gourraud, P.-A., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003926 · Cited by 312
Complement genes contribute sex-biased vulnerability in diverse disorders
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Kamitaki, N., Sekar, A., Handsaker, R. E., de Rivera, H., Tooley, K., Morris, D. L., Taylor, K. E., Whelan, C. W., Tombleson, P., et al. (2020) · Nature · doi:10.1038/s41586-020-2277-x · Cited by 238
Li, Y. R., & Keating, B. J. (2014) · Genome Medicine · doi:10.1186/s13073-014-0091-5 · Cited by 214
Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations
Barrie, W., Yang, Y., Irving-Pease, E. K., Attfield, K. E., Scorrano, G., Jensen, L. T., Armen, A. P., Dimopoulos, E. A., Stern, A., Refoyo-Martinez, A., et al. (2024) · Nature · doi:10.1038/s41586-023-06618-z · Cited by 161
Mechanisms involved in triggering rheumatoid arthritis
Catrina, A. I., Joshua, V., Klareskog, L., & Malmström, V. (2016) · Immunological Reviews · doi:10.1111/imr.12379 · Cited by 160
Self-citationKarnes, J. H., Bastarache, L., Shaffer, C. M., Gaudieri, S., Xu, Y., Glazer, A. M., Mosley, J. D., Zhao, S., Raychaudhuri, S., Mallal, S., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aai8708 · Cited by 126
Self-citationArthritis flares mediated by tissue-resident memory T cells in the joint
Chang, M. H., Levescot, A., Nelson-Maney, N., Blaustein, R. B., Winden, K. D., Morris, A., Wactor, A., Balu, S., Grieshaber-Bouyer, R., Wei, K., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109902 · Cited by 115
Using GWAS to identify genetic predisposition in hepatic autoimmunity
Webb, G. J., & Hirschfield, G. M. (2016) · Journal of Autoimmunity · doi:10.1016/j.jaut.2015.08.016 · Cited by 108
Interpreting the role of de novo protein-coding mutations in neuropsychiatric disease
Gratten, J., Visscher, P. M., Mowry, B. J., & Wray, N. R. (2013) · Nature Genetics · doi:10.1038/ng.2555 · Cited by 77
Mapping the dynamic genetic regulatory architecture of HLA genes at single-cell resolution
Kang, J. B., Shen, A. Z., Gurajala, S., Nathan, A., Rumker, L., Aguiar, V. R. C., Valencia, C., Lagattuta, K. A., Zhang, F., Jonsson, A. H., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01586-6 · Cited by 49
Self-citationGe, C., Weisse, S., Xu, B., Dobritzsch, D., Viljanen, J., Kihlberg, J., Do, N.-N., Schneider, N., Lanig, H., Holmdahl, R., et al. (2022) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2021-220500 · Cited by 26
Metadata
- Authors
- Raychaudhuri, S., Sandor, C., Stahl, E. A., Freudenberg, J., Lee, H.-S., Jia, X., Alfredsson, L., Padyukov, L., Klareskog, L., Worthington, J., Siminovitch, K. A., Bae, S.-C., Plenge, R. M., Gregersen, P. K., & de Bakker, P. I. W.
- Venue
- Nature Genetics
- Published
- 2012-01-29
- Volume
- 44
- Issue
- 3
- Pages
- 291-296
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2016370312
- Cited by
- 946
- References
- 3
- FWCI
- 52.69
- Type
- journal article
- Language
- en
- Open access
- green
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