Corrigendum: integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance

Publication type

Journal Article

Authors

Publication date

June 1, 2017

Summary:

Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

Published in

Nature Genetics

Volume and page numbers

Volume: 49 , p.317 -317

DOI

https://dx.doi.org/10.1038/ng0217-317c

ISSN

10614036

Subjects

#524210


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  • Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance

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    2. Pawan Gulati
    3. Felix R. Day
    4. Felicity Payne
    5. Halit Ongen
    6. Martijn van de Bunt
    7. Kyle J. Gaulton
    8. John D. Eicher
    9. Stephen J. Sharp
    10. Jian'an Luan
    11. Emanuella De Lucia Rolfe
    12. Isobel D. Stewart
    13. Eleanor Wheeler
    14. Sara M. Willems
    15. Claire Adams
    16. Hanieh Yaghootkar
    17. Nita G. Forouhi
    18. Kay-Tee Khaw
    19. Andrew D. Johnson
    20. Robert K. Semple
    21. Timothy Frayling
    22. John R. B. Perry
    23. Emmanouil Dermitzakis
    24. Mark I. McCarthy
    25. Ines Barroso
    26. Nicholas J. Wareham
    27. David B. Savage
    28. Claudia Langenberg
    29. Stephen O'Rahilly
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    Journal Article
    June 1, 2017

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