Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/132664
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Type: | Journal article |
Title: | Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease |
Author: | Emdin, C.A. Khera, A.V. Chaffin, M. Klarin, D. Natarajan, P. Aragam, K. Haas, M. Bick, A. Zekavat, S.M. Nomura, A. Ardissino, D. Wilson, J.G. Schunkert, H. McPherson, R. Watkins, H. Elosua, R. Bown, M.J. Samani, N.J. Baber, U. Erdmann, J. et al. |
Citation: | Nature Communications, 2018; 9(1):1613-1-1613-8 |
Publisher: | Nature Publishing Group |
Issue Date: | 2018 |
ISSN: | 2041-1723 2041-1723 |
Statement of Responsibility: | Connor A. Emdin, Amit V. Khera, Mark Chaffin, Derek Klarin, Pradeep Natarajan, Krishna Aragam ... et al. |
Abstract: | Less than 3% of protein-coding genetic variants are predicted to result in loss of protein function through the introduction of a stop codon, frameshift, or the disruption of an essential splice site; however, such predicted loss-of-function (pLOF) variants provide insight into effector transcript and direction of biological effect. In >400,000 UK Biobank participants, we conduct association analyses of 3759 pLOF variants with six metabolic traits, six cardiometabolic diseases, and twelve additional diseases. We identified 18 new low-frequency or rare (allele frequency < 5%) pLOF variant-phenotype associations. pLOF variants in the gene GPR151 protect against obesity and type 2 diabetes, in the gene IL33 against asthma and allergic disease, and in the gene IFIH1 against hypothyroidism. In the gene PDE3B, pLOF variants associate with elevated height, improved body fat distribution and protection from coronary artery disease. Our findings prioritize genes for which pharmacologic mimics of pLOF variants may lower risk for disease. |
Keywords: | Humans Respiratory Hypersensitivity Diabetes Mellitus, Type 2 Obesity Disease Proteins Gene Frequency Phenotype Databases, Genetic Genetic Variation Genetic Testing United Kingdom |
Rights: | © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. |
DOI: | 10.1038/s41467-018-03911-8 |
Grant ID: | HHSN268201500003I N01-HC-95159 N01-HC-95160 N01-HC-95161 N01-HC-95162 N01-HC-95163 N01-HC-95164 N01-HC-95165 N01-HC-95166 N01-HC-95167 N01-HC-95168 N01-HC-95169 UL1-TR-000040 UL1-TR-001079 UL1-TR-001420 UL1-TR-001881 DK063491 |
Published version: | http://dx.doi.org/10.1038/s41467-018-03911-8 |
Appears in Collections: | Medicine publications |
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hdl_132664.pdf | Published version | 811.79 kB | Adobe PDF | View/Open |
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