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

Zhen Qiao, Julia Sidorenko, Joana A. Revez, Angli Xue, Xueling Lu, Katri Pärna, Harold Snieder, Peter M. Visscher, Naomi R. Wray and Loic Yengo ()
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Zhen Qiao: Garvan Institute of Medical Research
Julia Sidorenko: The University of Queensland
Joana A. Revez: The University of Queensland
Angli Xue: Garvan Institute of Medical Research
Xueling Lu: University of Groningen, University Medical Center Groningen
Katri Pärna: University of Groningen, University Medical Center Groningen
Harold Snieder: University of Groningen, University Medical Center Groningen
Peter M. Visscher: The University of Queensland
Naomi R. Wray: The University of Queensland
Loic Yengo: The University of Queensland

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract 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 (h2 = 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.

Date: 2023
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DOI: 10.1038/s41467-023-36013-1

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