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

Lifelines Cohort Study, Zhen Qiao, Julia Sidorenko, Joana A. Revez, Angli Xue, Xueling Lu, Katri Pärna, Harold Snieder, Peter M. Visscher, Naomi R. Wray, Loic Yengo*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

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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.

Originele taal-2English
Aantal pagina's11
TijdschriftNature Communications
StatusPublished - 27-jan.-2023

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