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Cited by 585

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.

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

Open access
EPIC-InterAct Consortium, Lotta, Luca A, Cambridge FPLD1 Consortium, Gulati, Pawan, Day, Felix R, Payne, Felicity, Ongen, Halit, van de Bunt, Martijn, Gaulton, Kyle J, Eicher, John D, Sharp, Stephen J, Luan, Jian'an, De Lucia Rolfe, Emanuella, Stewart, Isobel D, Wheeler, Eleanor, Willems, Sara M, Adams, Claire, Yaghootkar, Hanieh, Forouhi, Nita G, Khaw, Kay-Tee, Johnson, Andrew D, Semple, Robert K, Frayling, Timothy, Perry, John R B, Dermitzakis, Emmanouil, McCarthy, Mark I, Barroso, Inês, Wareham, Nicholas J, Savage, David B, Langenberg, Claudia, O'Rahilly, Stephen, Scott, Robert A·2017·Nature Genetics

Abstract

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.

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Metadata

Authors
EPIC-InterAct Consortium, Lotta, L. A., Cambridge FPLD1 Consortium, Gulati, P., Day, F. R., Payne, F., Ongen, H., van de Bunt, M., Gaulton, K. J., Eicher, J. D., Sharp, S. J., Luan, J., De Lucia Rolfe, E., Stewart, I. D., Wheeler, E., Willems, S. M., Adams, C., Yaghootkar, H., Forouhi, N. G., Khaw, K.-T., Johnson, A. D., Semple, R. K., Frayling, T., Perry, J. R. B., Dermitzakis, E., McCarthy, M. I., Barroso, I., Wareham, N. J., Savage, D. B., Langenberg, C., O'Rahilly, S., & Scott, R. A.
Venue
Nature Genetics
Published
2016-11-14
Volume
49
Issue
1
Pages
17-26
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W2551499720
Cited by
585
References
44
FWCI
43.79
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. https://app.cochat.ai/papers/10.1038/ng.3714
The paper
EPIC-InterAct Consortium, Lotta, L. A., Cambridge FPLD1 Consortium, Gulati, P., Day, F. R., Payne, F., Ongen, H., van de Bunt, M., Gaulton, K. J., Eicher, J. D., Sharp, S. J., Luan, J., De Lucia Rolfe, E., Stewart, I. D., Wheeler, E., Willems, S. M., Adams, C., Yaghootkar, H., Forouhi, N. G., . . . Scott, R. A. (2017). Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nature Genetics. https://doi.org/10.1038/ng.3714

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.