基于血液的全基因组 DNA 甲基化与体脂肪和肥胖相关生化特征的相关性。
Blood-based genome-wide DNA methylation correlations across body-fat- and adiposity-related biochemical traits.
机构信息
Institute for Molecular Bioscience, Brisbane, Australia.
Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
出版信息
Am J Hum Genet. 2023 Sep 7;110(9):1564-1573. doi: 10.1016/j.ajhg.2023.08.004. Epub 2023 Aug 30.
The recent increase in obesity levels across many countries is likely to be driven by nongenetic factors. The epigenetic modification DNA methylation (DNAm) may help to explore this, as it is sensitive to both genetic and environmental exposures. While the relationship between DNAm and body-fat traits has been extensively studied, there is limited literature on the shared associations of DNAm variation across such traits. Akin to genetic correlation estimates, here, we introduce an approach to evaluate the similarities in DNAm associations between traits: DNAm correlations. As DNAm can be both a cause and consequence of complex traits, DNAm correlations have the potential to provide insights into trait relationships above that currently obtained from genetic and phenotypic correlations. Utilizing 7,519 unrelated individuals from Generation Scotland with DNAm from the EPIC array, we calculated DNAm correlations between body-fat- and adiposity-related traits by using the bivariate OREML framework in the OSCA software. For each trait, we also estimated the shared contribution of DNAm between sexes. We identified strong, positive DNAm correlations between each of the body-fat traits (BMI, body-fat percentage, and waist-to-hip ratio, ranging from 0.96 to 1.00), finding larger associations than those identified by genetic and phenotypic correlations. We identified a significant deviation from 1 in the DNAm correlations for BMI between males and females, with sex-specific DNAm changes associated with BMI identified at eight DNAm probes. Employing genome-wide DNAm correlations to evaluate the similarities in the associations of DNAm with complex traits has provided insight into obesity-related traits beyond that provided by genetic correlations.
近年来,许多国家的肥胖水平不断上升,这可能是由非遗传因素驱动的。表观遗传修饰 DNA 甲基化 (DNAm) 可能有助于探索这一点,因为它对遗传和环境暴露都很敏感。虽然 DNAm 与体脂肪特征之间的关系已经得到了广泛的研究,但关于 DNAm 变异在这些特征之间的共享关联的文献有限。类似于遗传相关估计,我们在这里引入了一种评估特征之间 DNAm 关联相似性的方法:DNAm 相关性。由于 DNAm 既可以是复杂特征的原因,也可以是其结果,因此 DNAm 相关性有可能提供比从遗传和表型相关性中获得的更多的关于特征关系的见解。利用来自苏格兰世代研究的 7519 名无血缘关系的个体和 EPIC 阵列的 DNAm,我们通过 OSCA 软件中的二元 OREML 框架计算了体脂肪和肥胖相关特征之间的 DNAm 相关性。对于每个特征,我们还估计了性别之间 DNAm 的共享贡献。我们发现,体脂肪特征(BMI、体脂肪百分比和腰臀比)之间存在强烈的正 DNAm 相关性(范围从 0.96 到 1.00),与遗传和表型相关性相比,这些相关性更强。我们发现,男性和女性之间 BMI 的 DNAm 相关性明显偏离 1,在 8 个 DNAm 探针中发现了与 BMI 相关的性别特异性 DNAm 变化。利用全基因组 DNAm 相关性评估 DNAm 与复杂特征的关联相似性,为肥胖相关特征提供了比遗传相关性提供的更深入的见解。
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