Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Aging Cell. 2024 Sep;23(9):e14241. doi: 10.1111/acel.14241. Epub 2024 Jun 28.
In adults, polygenic scores (PGSs) of telomere length (TL) alleles explain about 4.5% of the variance in TL, as measured by quantitative polymerase chain reaction (qPCR). Yet, these PGSs strongly infer a causal role of telomeres in aging-related diseases. To better understand the determinants of TL through the lifespan, it is essential to examine to what extent these PGSs explain TL in newborns. This study investigates the effect of PGSs on TL in both newborns and their parents, with TL measured by Southern blotting and expressed in base-pairs (bp). Additionally, the study explores the impact of PGSs related to transmitted or non-transmitted alleles on TL in newborns. For parents and newborns, the PGS effects on TL were 172 bp (p = 2.03 × 10) and 161 bp (p = 3.06 × 10), explaining 6.6% and 5.2% of the TL variance, respectively. The strongest PGS effect was shown for maternally transmitted alleles in newborn girls, amounting to 214 bp (p = 3.77 × 10) and explaining 7.8% of the TL variance. The PGS effect of non-transmitted alleles was 56 bp (p = 0.0593) and explained 0.6% of the TL variance. Our findings highlight the importance of TL genetics in understanding early-life determinants of TL. They point to the potential utility of PGSs composed of TL alleles in identifying susceptibility to aging-related diseases from birth and reveal the presence of sexual dimorphism in the effect of TL alleles on TL in newborns. Finally, we attribute the higher TL variance explained by PGSs in our study to TL measurement by Southern blotting.
在成年人中，通过定量聚合酶链反应（qPCR）测量的端粒长度（TL）等位基因的多基因评分（PGS）解释了 TL 变异的约 4.5%。然而，这些 PGS 强烈暗示端粒在与衰老相关的疾病中具有因果作用。为了更好地理解通过寿命影响 TL 的决定因素，检查这些 PGS 在新生儿中解释 TL 的程度至关重要。本研究通过 Southern 印迹法测量端粒并以碱基对（bp）表示，调查了 PGS 对新生儿及其父母 TL 的影响。此外，该研究还探讨了与传递或非传递等位基因相关的 PGS 对新生儿 TL 的影响。对于父母和新生儿，PGS 对 TL 的影响分别为 172 bp（p=2.03×10）和 161 bp（p=3.06×10），分别解释了 TL 变异的 6.6%和 5.2%。在新生女孩中，母系传递等位基因的 PGS 效应最强，达到 214 bp（p=3.77×10），解释了 TL 变异的 7.8%。非传递等位基因的 PGS 效应为 56 bp（p=0.0593），解释了 TL 变异的 0.6%。我们的研究结果强调了 TL 遗传学在理解 TL 早期生命决定因素中的重要性。它们表明由 TL 等位基因组成的 PGS 有可能从出生时识别与衰老相关疾病的易感性，并揭示了 TL 等位基因对新生儿 TL 影响中的性别二态性。最后，我们将我们研究中 PGS 解释的 TL 方差更高归因于 Southern 印迹法测量的 TL。
