Department of Nutritional Sciences, University of Georgia, 305 Sanford Drive, Athens, GA, 30602, USA.
Department of Genetics, University of Georgia, Athens, GA, 30602, USA.
BMC Genomics. 2024 Sep 6;25(1):837. doi: 10.1186/s12864-024-10710-7.
Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-β (TGF-β) superfamily that has gained considerable attention over the last decade for its observed ability to reverse age-related deterioration of multiple tissues, including the heart. Yet as many researchers have struggled to confirm the cardioprotective and anti-aging effects of GDF11, the topic has grown increasingly controversial, and the field has reached an impasse. We postulated that a clearer understanding of GDF11 could be gained by investigating its health effects at the population level.
We employed a comprehensive strategy to interrogate results from genome-wide association studies in population Biobanks. Interestingly, phenome-wide association studies (PheWAS) of GDF11 tissue-specific cis-eQTLs revealed associations with asthma, immune function, lung function, and thyroid phenotypes. Furthermore, PheWAS of GDF11 genetic variants confirmed these results, revealing similar associations with asthma, immune function, lung function, and thyroid health. To complement these findings, we mined results from transcriptome-wide association studies, which uncovered associations between predicted tissue-specific GDF11 expression and the same health effects identified from PheWAS analyses.
In this study, we report novel relationships between GDF11 and disease, namely asthma and hypothyroidism, in contrast to its formerly assumed role as a rejuvenating factor in basic aging and cardiovascular health. We propose that these associations are mediated through the involvement of GDF11 in inflammatory signaling pathways. Taken together, these findings provide new insights into the health effects of GDF11 at the population level and warrant future studies investigating the role of GDF11 in these specific health conditions.
生长分化因子 11（GDF11）是转化生长因子-β（TGF-β）超家族的成员，在过去十年中，由于其观察到的逆转多种组织（包括心脏）与年龄相关的恶化的能力而引起了相当大的关注。然而，由于许多研究人员难以证实 GDF11 的心脏保护和抗衰老作用，该主题变得越来越有争议，该领域已经陷入僵局。我们假设通过在人群水平上研究 GDF11 的健康影响，可以更清楚地了解 GDF11。
我们采用了一种全面的策略来研究人群生物库中的全基因组关联研究结果。有趣的是，GDF11 组织特异性顺式-eQTL 的表型全基因组关联研究（PheWAS）显示与哮喘、免疫功能、肺功能和甲状腺表型相关。此外，GDF11 遗传变异的 PheWAS 证实了这些结果，显示出与哮喘、免疫功能、肺功能和甲状腺健康相似的关联。为了补充这些发现，我们挖掘了转录组全基因组关联研究的结果，这些研究发现了预测组织特异性 GDF11 表达与从 PheWAS 分析中确定的相同健康影响之间的关联。
在这项研究中，我们报告了 GDF11 与疾病之间的新关系，即哮喘和甲状腺功能减退症，与以前假设的 GDF11 在基本衰老和心血管健康中的抗衰老作用形成对比。我们提出，这些关联是通过 GDF11 参与炎症信号通路介导的。总之，这些发现为人群水平上 GDF11 的健康影响提供了新的见解，并需要进一步研究 GDF11 在这些特定健康状况中的作用。
