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Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose

The genetic regulation of post-prandial glucose levels is poorly understood. Here, we characterise the genetic architecture of blood glucose variably measured within 0 and 24 h of fasting in 368,000 European ancestry participants of the UK Biobank. We found a near-linear increase in the heritability...

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Autores principales: Qiao, Zhen, Sidorenko, Julia, Revez, Joana A., Xue, Angli, Lu, Xueling, Pärna, Katri, Snieder, Harold, Visscher, Peter M., Wray, Naomi R., Yengo, Loic
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883484/
https://www.ncbi.nlm.nih.gov/pubmed/36707517
http://dx.doi.org/10.1038/s41467-023-36013-1
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author Qiao, Zhen
Sidorenko, Julia
Revez, Joana A.
Xue, Angli
Lu, Xueling
Pärna, Katri
Snieder, Harold
Visscher, Peter M.
Wray, Naomi R.
Yengo, Loic
author_facet Qiao, Zhen
Sidorenko, Julia
Revez, Joana A.
Xue, Angli
Lu, Xueling
Pärna, Katri
Snieder, Harold
Visscher, Peter M.
Wray, Naomi R.
Yengo, Loic
author_sort Qiao, Zhen
collection PubMed
description The genetic regulation of post-prandial glucose levels is poorly understood. Here, we characterise the genetic architecture of blood glucose variably measured within 0 and 24 h of fasting in 368,000 European ancestry participants of the UK Biobank. We found a near-linear increase in the heritability of non-fasting glucose levels over time, which plateaus to its fasting state value after 5 h post meal (h(2) = 11%; standard error: 1%). The genetic correlation between different fasting times is > 0.77, suggesting that the genetic control of glucose is largely constant across fasting durations. Accounting for heritability differences between fasting times leads to a ~16% improvement in the discovery of genetic variants associated with glucose. Newly detected variants improve the prediction of fasting glucose and type 2 diabetes in independent samples. Finally, we meta-analysed summary statistics from genome-wide association studies of random and fasting glucose (N = 518,615) and identified 156 independent SNPs explaining 3% of fasting glucose variance. Altogether, our study demonstrates the utility of random glucose measures to improve the discovery of genetic variants associated with glucose homeostasis, even in fasting conditions.
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spelling pubmed-98834842023-01-29 Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose Qiao, Zhen Sidorenko, Julia Revez, Joana A. Xue, Angli Lu, Xueling Pärna, Katri Snieder, Harold Visscher, Peter M. Wray, Naomi R. Yengo, Loic Nat Commun Article The genetic regulation of post-prandial glucose levels is poorly understood. Here, we characterise the genetic architecture of blood glucose variably measured within 0 and 24 h of fasting in 368,000 European ancestry participants of the UK Biobank. We found a near-linear increase in the heritability of non-fasting glucose levels over time, which plateaus to its fasting state value after 5 h post meal (h(2) = 11%; standard error: 1%). The genetic correlation between different fasting times is > 0.77, suggesting that the genetic control of glucose is largely constant across fasting durations. Accounting for heritability differences between fasting times leads to a ~16% improvement in the discovery of genetic variants associated with glucose. Newly detected variants improve the prediction of fasting glucose and type 2 diabetes in independent samples. Finally, we meta-analysed summary statistics from genome-wide association studies of random and fasting glucose (N = 518,615) and identified 156 independent SNPs explaining 3% of fasting glucose variance. Altogether, our study demonstrates the utility of random glucose measures to improve the discovery of genetic variants associated with glucose homeostasis, even in fasting conditions. Nature Publishing Group UK 2023-01-27 /pmc/articles/PMC9883484/ /pubmed/36707517 http://dx.doi.org/10.1038/s41467-023-36013-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Qiao, Zhen
Sidorenko, Julia
Revez, Joana A.
Xue, Angli
Lu, Xueling
Pärna, Katri
Snieder, Harold
Visscher, Peter M.
Wray, Naomi R.
Yengo, Loic
Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose
title Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose
title_full Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose
title_fullStr Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose
title_full_unstemmed Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose
title_short Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose
title_sort estimation and implications of the genetic architecture of fasting and non-fasting blood glucose
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883484/
https://www.ncbi.nlm.nih.gov/pubmed/36707517
http://dx.doi.org/10.1038/s41467-023-36013-1
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