Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers (original) (raw)

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Acknowledgements

This research uses resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases (NIAID), the National Human Genome Research Institute (NHGRI), the National Institute of Child Health and Human Development (NICHD) and JDRF and supported by grant U01 DK062418 from the US National Institutes of Health. Further support was provided by grants from the NIDDK (DK046635 and DK085678) to P.C. and by a joint JDRF and Wellcome Trust grant (WT061858/09115) to the Diabetes and Inflammation Laboratory at Cambridge University, which also received support from the NIHR Cambridge Biomedical Research Centre. ImmunoBase receives support from Eli Lilly and Company. C.W. and H.G. are funded by the Wellcome Trust (089989). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140).

We gratefully acknowledge the following groups and individuals who provided biological samples or data for this study. We obtained DNA samples from the British 1958 Birth Cohort collection, funded by the UK Medical Research Council and the Wellcome Trust. We acknowledge use of DNA samples from the NIHR Cambridge BioResource. We thank volunteers for their support and participation in the Cambridge BioResource and members of the Cambridge BioResource Scientific Advisory Board (SAB) and Management Committee for their support of our study. We acknowledge the NIHR Cambridge Biomedical Research Centre for funding. Access to Cambridge BioResource volunteers and to their data and samples are governed by the Cambridge BioResource SAB. Documents describing access arrangements and contact details are available at http://www.cambridgebioresource.org.uk/. We thank the Avon Longitudinal Study of Parents and Children laboratory in Bristol, UK, and the British 1958 Birth Cohort team, including S. Ring, R. Jones, M. Pembrey, W. McArdle, D. Strachan and P. Burton, for preparing and providing the control DNA samples. This study makes use of data generated by the Wellcome Trust Case Control Consortium, funded by Wellcome Trust award 076113; a full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk/.

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Author notes

1. Patrick Concannon
   Present address: Present address: University of Florida Genetics Institute and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USA.,
2. Suna Onengut-Gumuscu, Wei-Min Chen and Oliver Burren: These authors contributed equally to this work.
3. John A Todd, Chris Wallace, Patrick Concannon and Stephen S Rich: These authors jointly supervised this work.

Authors and Affiliations

1. Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA
   Suna Onengut-Gumuscu, Wei-Min Chen, Aaron R Quinlan, Josyf C Mychaleckyj, Emily Farber, Jessica K Bonnie, Michal Szpak, Patrick Concannon & Stephen S Rich
2. Department of Medicine, Division of Endocrinology, University of Virginia, Charlottesville, Virginia, USA
   Suna Onengut-Gumuscu
3. Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, Virginia, USA
   Wei-Min Chen, Aaron R Quinlan, Josyf C Mychaleckyj & Stephen S Rich
4. Department of Medical Genetics, Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
   Oliver Burren, Nick J Cooper, Ellen Schofield, Premanand Achuthan, Hui Guo, Mary D Fortune, Helen Stevens, Neil M Walker, Jason D Cooper, John A Todd & Chris Wallace
5. Department of Computer Science, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA
   Lucas D Ward, Anshul Kundaje & Manolis Kellis
6. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
   Lucas D Ward, Anshul Kundaje, Manolis Kellis & Mark J Daly
7. Department of Genetics, Stanford University, Stanford, California, USA
   Anshul Kundaje
8. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
   Anshul Kundaje & Mark J Daly
9. Wellcome Trust Sanger Institute, Hinxton, UK
   Jeffrey C Barrett & Panos Deloukas
10. Medical Research Council (MRC) Biostatistics Unit, Institute of Public Health, University Forvie Site, Cambridge, UK
    Chris Wallace

Authors

1. Suna Onengut-Gumuscu
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2. Wei-Min Chen
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3. Oliver Burren
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4. Nick J Cooper
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5. Aaron R Quinlan
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6. Josyf C Mychaleckyj
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7. Emily Farber
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8. Jessica K Bonnie
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9. Michal Szpak
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10. Ellen Schofield
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11. Premanand Achuthan
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12. Hui Guo
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13. Mary D Fortune
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14. Helen Stevens
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15. Neil M Walker
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16. Lucas D Ward
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17. Anshul Kundaje
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18. Manolis Kellis
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19. Mark J Daly
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20. Jeffrey C Barrett
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21. Jason D Cooper
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22. Panos Deloukas
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23. John A Todd
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24. Chris Wallace
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25. Patrick Concannon
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26. Stephen S Rich
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Consortia

Type 1 Diabetes Genetics Consortium

Contributions

The study was conceptually designed by M.J.D., J.C.B., P.D., J.A.T., C.W., P.C. and S.S.R. The study was implemented by S.O.-G., E.F., H.S., N.M.W., P.D., T1DGC, J.A.T., C.W., P.C. and S.S.R. DNA samples were managed by S.O.-G., E.F. and H.S. Genotyping and laboratory quality control were conducted by S.O.-G., E.F. and P.D. Statistical quality control methods were implemented by W.-M.C., M.S., N.J.C., H.G. and J.C.M. Statistical analyses were performed by W.-M.C., A.R.Q., J.C.M., J.D.C., O.B., J.K.B., N.J.C., M.D.F. and C.W. Chromatin state analyses were conducted by O.B., L.D.W., A.K. and M.K. ImmunoBase is maintained by O.B., E.S. and P.A. The manuscript was written by S.O.-G., W.-M.C., A.R.Q., O.B., J.A.T., C.W., P.C. and S.S.R. All authors reviewed and contributed on the final manuscript.

Corresponding author

Correspondence toStephen S Rich.

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The authors declare no competing financial interests.

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A complete list of members and affiliations is provided in the Supplementary Note.

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Onengut-Gumuscu, S., Chen, WM., Burren, O. et al. Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.Nat Genet 47, 381–386 (2015). https://doi.org/10.1038/ng.3245

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• Received: 04 May 2014
• Accepted: 13 February 2015
• Published: 09 March 2015
• Issue Date: April 2015
• DOI: https://doi.org/10.1038/ng.3245