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Research Article

Genomics Meets Glycomics—The First GWAS Study of Human N-Glycome Identifies HNF1α as a Master Regulator of Plasma Protein Fucosylation

  • Gordan Lauc equal contributor,

    equal contributor Contributed equally to this work with: Gordan Lauc, Abdelkader Essafi, Jennifer E. Huffman, Caroline Hayward

    Affiliations: Glycobiology Laboratory, Genos Ltd., Zagreb, Croatia, Department of Biochemistry and Molecular Biology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia

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  • Abdelkader Essafi equal contributor,

    equal contributor Contributed equally to this work with: Gordan Lauc, Abdelkader Essafi, Jennifer E. Huffman, Caroline Hayward

    Affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom

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  • Jennifer E. Huffman equal contributor,

    equal contributor Contributed equally to this work with: Gordan Lauc, Abdelkader Essafi, Jennifer E. Huffman, Caroline Hayward

    Affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom

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  • Caroline Hayward equal contributor,

    equal contributor Contributed equally to this work with: Gordan Lauc, Abdelkader Essafi, Jennifer E. Huffman, Caroline Hayward

    Affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom

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  • Ana Knežević,

    Affiliation: Department of Biochemistry and Molecular Biology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia

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  • Jayesh J. Kattla,

    Affiliations: National Institute for Bioprocessing Research and Training, Dublin-Oxford Glycobiology Lab, Conway Institute, University College Dublin, Dublin, Ireland, Conway Institute, University College Dublin, Dublin, Ireland

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  • Ozren Polašek,

    Affiliations: Gen Info Ltd., Zagreb, Croatia, Medical School, University of Zagreb, Zagreb, Croatia

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  • Olga Gornik,

    Affiliation: Department of Biochemistry and Molecular Biology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia

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  • Veronique Vitart,

    Affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom

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  • Jodie L. Abrahams,

    Affiliations: National Institute for Bioprocessing Research and Training, Dublin-Oxford Glycobiology Lab, Conway Institute, University College Dublin, Dublin, Ireland, Conway Institute, University College Dublin, Dublin, Ireland

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  • Maja Pučić,

    Affiliation: Glycobiology Laboratory, Genos Ltd., Zagreb, Croatia

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  • Mislav Novokmet,

    Affiliation: Glycobiology Laboratory, Genos Ltd., Zagreb, Croatia

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  • Irma Redžić,

    Affiliation: Department of Biochemistry and Molecular Biology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia

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  • Susan Campbell,

    Affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom

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  • Sarah H. Wild,

    Affiliation: Centre for Population Health Sciences, The University of Edinburgh Medical School, Edinburgh, United Kingdom

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  • Fran Borovečki,

    Affiliation: Medical School, University of Zagreb, Zagreb, Croatia

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  • Wei Wang,

    Affiliations: School of Public Health and Family Medicine, Capital Medical University, Beijing, China, Graduate School of the Chinese Academy of Sciences, Beijing, China, Croatian Centre for Global Health, University of Split Medical School, Split, Croatia

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  • Ivana Kolčić,

    Affiliation: Medical School, University of Zagreb, Zagreb, Croatia

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  • Lina Zgaga,

    Affiliation: Medical School, University of Zagreb, Zagreb, Croatia

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  • Ulf Gyllensten,

    Affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

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  • James F. Wilson ,

    Affiliation: Centre for Population Health Sciences, The University of Edinburgh Medical School, Edinburgh, United Kingdom

    These authors also contributed equally to this work.

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  • Alan F. Wright ,

    Affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom

    These authors also contributed equally to this work.

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  • Nicholas D. Hastie ,

    Affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom

    These authors also contributed equally to this work.

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  • Harry Campbell ,

    Affiliation: Centre for Population Health Sciences, The University of Edinburgh Medical School, Edinburgh, United Kingdom

    These authors also contributed equally to this work.

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  • Pauline M. Rudd ,

    Affiliations: National Institute for Bioprocessing Research and Training, Dublin-Oxford Glycobiology Lab, Conway Institute, University College Dublin, Dublin, Ireland, Conway Institute, University College Dublin, Dublin, Ireland

    These authors also contributed equally to this work.

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  • Igor Rudan mail

    irudan@hotmail.com

    Affiliations: Centre for Population Health Sciences, The University of Edinburgh Medical School, Edinburgh, United Kingdom, Croatian Centre for Global Health, University of Split Medical School, Split, Croatia

    These authors also contributed equally to this work.

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  • Published: December 23, 2010
  • DOI: 10.1371/journal.pgen.1001256

About the Authors

Gordan Lauc, Maja Pučić, Mislav Novokmet
Glycobiology Laboratory, Genos Ltd., Zagreb, Croatia
Gordan Lauc, Ana Knežević, Olga Gornik, Irma Redžić
Department of Biochemistry and Molecular Biology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
Abdelkader Essafi, Jennifer E. Huffman, Caroline Hayward, Veronique Vitart, Susan Campbell, Alan F. Wright, Nicholas D. Hastie
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom
Jayesh J. Kattla, Jodie L. Abrahams, Pauline M. Rudd
National Institute for Bioprocessing Research and Training, Dublin-Oxford Glycobiology Lab, Conway Institute, University College Dublin, Dublin, Ireland
Jayesh J. Kattla, Jodie L. Abrahams, Pauline M. Rudd
Conway Institute, University College Dublin, Dublin, Ireland
Ozren Polašek
Gen Info Ltd., Zagreb, Croatia
Ozren Polašek, Fran Borovečki, Ivana Kolčić, Lina Zgaga
Medical School, University of Zagreb, Zagreb, Croatia
Sarah H. Wild, James F. Wilson, Harry Campbell, Igor Rudan
Centre for Population Health Sciences, The University of Edinburgh Medical School, Edinburgh, United Kingdom
Wei Wang
School of Public Health and Family Medicine, Capital Medical University, Beijing, China
Wei Wang
Graduate School of the Chinese Academy of Sciences, Beijing, China
Wei Wang, Igor Rudan
Croatian Centre for Global Health, University of Split Medical School, Split, Croatia
Ulf Gyllensten
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

Corresponding Author

Email: irudan@hotmail.com

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

Conceived and designed the experiments: G Lauc, A Essafi, C Hayward, A Knezevic, O Gornik, U Gyllensten, JF Wilson, AF Wright, ND Hastie, H Campbell, PM Rudd, I Rudan. Performed the experiments: A Essafi, JE Huffman, A Knezevic, JJ Kattla, O Polasek, V Vitart, JL Abrahams, M Pucic, M Novokmet, I Redzic, SH Wild, F Borovecki, I Kolcic, L Zgaga. Analyzed the data: G Lauc, A Essafi, JE Huffman, C Hayward, A Knezevic, JJ Kattla, O Polasek, O Gornik, V Vitart, JL Abrahams, M Pucic, M Novokmet, I Redzic, S Campbell, SH Wild, F Borovecki, W Wang, I Kolcic, L Zgaga, U Gyllensten, JF Wilson, AF Wright, ND Hastie, H Campbell, PM Rudd, I Rudan. Contributed reagents/materials/analysis tools: G Lauc, C Hayward, O Polasek, V Vitart, S Campbell, F Borovecki, W Wang, I Kolcic, L Zgaga, U Gyllensten, JF Wilson, AF Wright, ND Hastie, H Campbell, PM Rudd, I Rudan. Wrote the paper: G Lauc, A Essafi, JE Huffman, C Hayward, O Gornik, V Vitart, U Gyllensten, JF Wilson, AF Wright, ND Hastie, H Campbell, PM Rudd, I Rudan. Led the writing of the paper: I Rudan, G Lauc. Performed functional genomic studies: A Essafi. Carried out the genotyping and performed statistical analyses: JE Huffman, C Hayward, V Vitart, S Campbell, SH Wild, F Borovecki. Performed laboratory analyses of glycans: A Knezevic, JJ Kattla, O Gornik, JL Abrahams, M Pucic, M Novokmet, I Rudan. Performed field work and constructed genealogies in Croatia: O Polasek, I Kolcic, L Zgaga. Assisted in writing of the paper and checked the manuscript for important intellectual content: W Wang, U Gyllensten, JF Wilson, AF Wright, ND Hastie, H Campbell, PM Rudd. Designed the study: U Gyllensten, JF Wilson, AF Wright, ND Hastie, H Campbell, PM Rudd, I Rudan, G Lauc.