On the Association Between Rheumatoid Arthritis and Classical HLA Class I and Class II Alleles Predicted from Single-nucleotide Polymorphism Data

Overview

Journal BMC Proc

Publisher Biomed Central

Specialty Biology

Date 2009 Dec 19

PMID 20018024

Citations 3

Authors

Mathieu Lemire

Affiliations

Soon will be listed here.

Abstract

Using single-nucleotide polymorphisms (SNPs), we sought to predict classical class I and class II human leukocyte antigen (HLA) alleles, and test for their associations with rheumatoid arthritis (RA) in the North American Rheumatoid Arthritis Consortium sample of cases and controls, genotyped on the Illumina HumanHap550 BeadChip. We use publicly available databases of SNP data and HLA data to find SNPs or SNP-haplotypes to be used as surrogates for each HLA allele. To reduce the confounding effects of linkage disequilibrium with the HLA-DRB1 locus, we tested for the association conditional on the presence or absence of a shared epitope allele on the same haplotype as the target HLA allele. Using SNP surrogates, we find that components of the DQ8 serotype (DQA1*0301:DQB1*0302) are associated with RA, irrespective of the presence or absence of a shared epitope allele on their respective haplotypes. Knowledge of the haplotype structure in the HLA region is still necessary for better interpretation of the results.

Citing Articles

Association of and gene polymorphisms and ERAP2 protein with the susceptibility and severity of rheumatoid arthritis in the Ukrainian population.

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Comparative study for haplotype block partitioning methods - Evidence from chromosome 6 of the North American Rheumatoid Arthritis Consortium (NARAC) dataset.

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Inference of high resolution HLA types using genome-wide RNA or DNA sequencing reads.

Bai Y, Ni M, Cooper B, Wei Y, Fury W BMC Genomics. 2014; 15:325.

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Haplotype-based analysis: a summary of GAW16 Group 4 analysis.

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References

Dudbridge F . Likelihood-based association analysis for nuclear families and unrelated subjects with missing genotype data. Hum Hered. 2008; 66(2):87-98. PMC: 2386559. DOI: 10.1159/000119108. View

Perdriger A . Do the HLA-DQ and DP genes play a role in rheumatoid arthritis?. Joint Bone Spine. 2001; 68(1):12-8. DOI: 10.1016/s1297-319x(00)00236-0. View

de Vries N, van Elderen C, Tijssen H, van Riel P, van de Putte L . No support for HLA-DQ encoded susceptibility in rheumatoid arthritis. Arthritis Rheum. 1999; 42(8):1621-7. DOI: 10.1002/1529-0131(199908)42:8<1621::AID-ANR9>3.0.CO;2-0. View

de Bakker P, Yelensky R, Peer I, Gabriel S, Daly M, Altshuler D . Efficiency and power in genetic association studies. Nat Genet. 2005; 37(11):1217-23. DOI: 10.1038/ng1669. View

Barrett J, Fry B, Maller J, Daly M . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2004; 21(2):263-5. DOI: 10.1093/bioinformatics/bth457. View

. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007; 447(7145):661-78. PMC: 2719288. DOI: 10.1038/nature05911. View

Plenge R, Cotsapas C, Davies L, Price A, de Bakker P, Maller J . Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat Genet. 2007; 39(12):1477-82. PMC: 2652744. DOI: 10.1038/ng.2007.27. View

Vos K, van der Horst-Bruinsma I, Hazes J, Breedveld F, le Cessie S, Schreuder G . Evidence for a protective role of the human leukocyte antigen class II region in early rheumatoid arthritis. Rheumatology (Oxford). 2001; 40(2):133-9. DOI: 10.1093/rheumatology/40.2.133. View

Gregersen P, Silver J, Winchester R . The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987; 30(11):1205-13. DOI: 10.1002/art.1780301102. View

10.

Jawaheer D, Li W, Graham R, Chen W, Damle A, Xiao X . Dissecting the genetic complexity of the association between human leukocyte antigens and rheumatoid arthritis. Am J Hum Genet. 2002; 71(3):585-94. PMC: 449696. DOI: 10.1086/342407. View

11.

Newton J, Harney S, Wordsworth B, Brown M . A review of the MHC genetics of rheumatoid arthritis. Genes Immun. 2004; 5(3):151-7. DOI: 10.1038/sj.gene.6364045. View

12.

Plenge R, Seielstad M, Padyukov L, Lee A, Remmers E, Ding B . TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study. N Engl J Med. 2007; 357(12):1199-209. PMC: 2636867. DOI: 10.1056/NEJMoa073491. View

13.

Tezenas du Montcel S, Michou L, Petit-Teixeira E, Osorio J, Lemaire I, Lasbleiz S . New classification of HLA-DRB1 alleles supports the shared epitope hypothesis of rheumatoid arthritis susceptibility. Arthritis Rheum. 2005; 52(4):1063-8. DOI: 10.1002/art.20989. View

14.

Begovich A, Carlton V, Honigberg L, Schrodi S, Chokkalingam A, Alexander H . A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet. 2004; 75(2):330-7. PMC: 1216068. DOI: 10.1086/422827. View

15.

Wang W, Barratt B, Clayton D, Todd J . Genome-wide association studies: theoretical and practical concerns. Nat Rev Genet. 2005; 6(2):109-18. DOI: 10.1038/nrg1522. View

16.

de Bakker P, McVean G, Sabeti P, Miretti M, Green T, Marchini J . A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC. Nat Genet. 2006; 38(10):1166-72. PMC: 2670196. DOI: 10.1038/ng1885. View

17.

Price A, Patterson N, Plenge R, Weinblatt M, Shadick N, Reich D . Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006; 38(8):904-9. DOI: 10.1038/ng1847. View