| Title: | Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose |
| Journal: | Nature Communications |
| Published: | 27 Jan 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36707517/ |
| DOI: | https://doi.org/10.1038/s41467-023-36013-1 |
| URL: | https://www.nature.com/articles/s41467-023-36013-1.pdf |
| Citations: | 2 (2 in last 2 years) as of 8 Aug 2024 |
Publication 11016
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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.</p>
10 Authors
- Zhen Qiao
- Julia Sidorenko
- Joana A. Revez
- Angli Xue
- Xueling Lu
- Katri Pärna
- Harold Snieder
- Peter M. Visscher
- Naomi R. Wray
- Loic Yengo
1 Application
| Application ID | Title |
|---|---|
| 12505 | Dissecting the genetic basis of relationships between early-life and later-life events |
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