A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC (original) (raw)

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Acknowledgements

The authors thank J. Oksenberg, P. De Jager and N. Walker for discussions and their critical reading of the manuscript. The authors are also grateful to B. Fry for technical assistance with the selection analysis. This project has been funded in whole or in part with federal funds from the US National Cancer Institute, National Institutes of Health (NIH), under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The Wellcome Trust supported the work of M.M., P.W., M.D., J.M., S.B., J.T., J.A.T. and P.D. The Juvenile Diabetes Research Foundation supported J.A.T. P.C.S. is funded by the Damon Runyon Cancer Fellowship. The International MS Genetics Consortium supported the work of D.H., S.G., M.P.V., and J.D.R. This work was also supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Allergy and Infectious Diseases (Autoimmunity Prevention Center grant U19 AI050864) to J.D.R.

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Author notes

1. Paul I W de Bakker, Gil McVean, Pardis C Sabeti and Marcos M Miretti: These authors contributed equally to this work.

Authors and Affiliations

1. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Seven Cambridge Center, Cambridge, 02142, Massachusetts, USA
   Paul I W de Bakker, Pardis C Sabeti, Todd Green, Angela Richardson, Emily C Walsh, David A Hafler, Mark J Daly & John D Rioux
2. Center for Human Genetic Research, Massachusetts General Hospital, Boston, 02114-2790, Massachusetts, USA
   Paul I W de Bakker & Mark J Daly
3. Department of Statistics, University of Oxford, Oxford, UK
   Gil McVean & Jonathan Marchini
4. Wellcome Trust Sanger Institute, Hinxton, UK
   Marcos M Miretti, Pamela Whittaker, Marcos Delgado, Jonathan Morrison, Stephan Beck & Panos Deloukas
5. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
   Xiayi Ke
6. Department of Medical Genetics, Complex Genetics Section, University Medical Center, Utrecht, The Netherlands
   Alienke J Monsuur & Cisca Wijmenga
7. Laboratory of Genomic Diversity, SAIC-Frederick, Inc. and National Cancer Institute–Frederick, Frederick, Maryland, USA
   Xiaojiang Gao & Mary Carrington
8. Illumina, Inc., San Diego, California, USA
   Luana Galver & Sarah Shaw Murray
9. Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, USA
   John Hart, Margaret Pericak-Vance & Simon Gregory
10. Center for Neurologic Diseases Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
    David A Hafler
11. Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
    John A Todd
12. Cambridge Institute for Medical Research, Addensbrookes Hospital, Hills Road, Cambridge, UK
    John Trowsdale
13. Imperial College of London, London, UK
    Tim J Vyse
14. Department of Medicine, Université de Montréal, Montréal, Québec, Canada
    John D Rioux
15. Montréal Heart Institute, Montréal, Québec, Canada
    John D Rioux

Authors

1. Paul I W de Bakker
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2. Gil McVean
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3. Pardis C Sabeti
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4. Marcos M Miretti
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5. Todd Green
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6. Jonathan Marchini
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7. Xiayi Ke
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8. Alienke J Monsuur
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9. Pamela Whittaker
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10. Marcos Delgado
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11. Jonathan Morrison
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12. Angela Richardson
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13. Emily C Walsh
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14. Xiaojiang Gao
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15. Luana Galver
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16. John Hart
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17. David A Hafler
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18. Margaret Pericak-Vance
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19. John A Todd
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20. Mark J Daly
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21. John Trowsdale
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22. Cisca Wijmenga
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23. Tim J Vyse
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24. Stephan Beck
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25. Sarah Shaw Murray
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26. Mary Carrington
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27. Simon Gregory
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28. Panos Deloukas
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29. John D Rioux
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Contributions

The study was designed by J.A.T., S.G., S.B., P.D. and J.D.R. Genotyping was performed by multiple groups (P.W., M.D., J.M., A.R., L.G., J.H., M.P.-V., S.S.M.). M.C. performed the HLA typing. A.J.M., C.W. and T.V. provided samples and genotype data for the cross-validation experiments. P.I.W.d.B., G.M., P.C.S., M.M., J.M., X.K., E.C.W. and T.G. performed analyses. The manuscript was written by P.I.W.d.B., G.M., P.C.S. and J.D.R., with contributions from J.A.T., D.A.H., M.J.D., M.C. and J.T. The genotyping, analysis and manuscript writing efforts of this international collaborative group were coordinated by J.D.R.

Corresponding author

Correspondence toJohn D Rioux.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Allelic association between SNPs across the 7.5-Mb extended MHC region and HLA types at each gene for the combined population data (using the 5,754 SNPs that were typed in all populations and are polymorphic across the combined population samples). (PDF 2374 kb)

Supplementary Fig. 2

A region of the MHC, including BAK1 and HLA-DPA1, contains one of the top 20 candidates for selection based on the long-range haplotype test in the YRI. (PDF 313 kb)

Supplementary Table 1

Partial summary of established HLA associations and associations of contemporary interest. (PDF 16 kb)

Supplementary Table 2

Correlations between alleles at the six classical HLA loci typed in the study. (PDF 4 kb)

Supplementary Table 3

List of tags for HLA alleles. (PDF 70 kb)

Supplementary Table 4

Cross-panel performance of HLA tags. (PDF 65 kb)

Supplementary Table 5

List of top-ranking SNPs and haplotypes with evidence for recent positive selection using EHH-based methods. (PDF 74 kb)

Supplementary Methods (PDF 30 kb)

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de Bakker, P., McVean, G., Sabeti, P. et al. A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC.Nat Genet 38, 1166–1172 (2006). https://doi.org/10.1038/ng1885

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• Received: 31 March 2006
• Accepted: 23 August 2006
• Published: 24 September 2006
• Issue Date: 01 October 2006
• DOI: https://doi.org/10.1038/ng1885