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

Autor: Qiao Z; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia., Sidorenko J; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia., Revez JA; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia., Xue A; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia., Lu X; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.; Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Guangdong, China., Pärna K; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.; Institute of Genomics, University of Tartu, Tartu, Estonia., Snieder H; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands., Visscher PM; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia., Wray NR; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.; Queensland Brain Institute, The University of Queensland, Brisbane, Australia., Yengo L; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia. l.yengodimbou@uq.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jan 27; Vol. 14 (1), pp. 451. Date of Electronic Publication: 2023 Jan 27.
DOI: 10.1038/s41467-023-36013-1
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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