双向两样本孟德尔随机化分析鉴定了初潮年龄与与骨骼肌减少症相关特征之间的因果关联。

Bidirectional two-sample mendelian randomization analysis identifies causal associations between age at menarche and sarcopenia-related traits.

机构信息

Graduate School, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China.

The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

出版信息

Genes Genomics. 2023 Aug;45(8):1085-1095. doi: 10.1007/s13258-023-01415-4. Epub 2023 Jul 5.

DOI:10.1007/s13258-023-01415-4

PMID:37405597

Abstract

BACKGROUND

Observational studies have shown that the age of menarche is associated with sarcopenia, but confounding factors make the causal relationship difficult to infer.

OBJECTIVE

Therefore, we conducted a bidirectional two-sample Mendelian randomized (MR) analysis to evaluate the potential causal relationship between age at menarche and sarcopenia-related traits (hand grip strength, lean mass, walking pace).

METHODS

We obtained the latest aggregate statistics from the Genome-wide association studies (GWAS) database on the age of menarche of 182,416 participants from ReproGen, the appendicular lean mass of 244,730 participants from EMBL's European Bioinformatics Institute, the left-hand grip strength of 401,026 participants, the right-hand grip strength of 461,089 participants and the usual walking pace of 459,915 participants from the UK Biobank. The inverse variance weighting (IVW) method and other MR methods were used to evaluate the bidirectional causal relationship between the age of menarche and sarcopenia.

RESULTS

The forward MR results showed that the age of menarche predicted by the gene was positively correlated with left-hand grip strength (IVW=0.041, P = 2.00 × 10), right-hand grip strength (IVW=0.053, P = 1.97 × 10), appendicular lean mass (IVW=0.012, P = 4.38 × 10) and usual walking pace (IVW=0.033, P = 1.62 × 10).In the reverse MR analysis, we also found that the usual walking pace was positively correlated with the age of menarche predicted by genes (IVW=0.532, P = 1.65 × 10). Still, there was no causal relationship between grip strength and appendicular lean mass and the age at menarche.

CONCLUSION

Our results show that earlier menarche will increase the risk of sarcopenia. In addition, people with higher muscle function tend to have menarche later. These findings may provide a reference for prevention strategies and interventions for menarche in advance and sarcopenia.

摘要

背景

观察性研究表明，初潮年龄与肌肉减少症有关，但混杂因素使得因果关系难以推断。

目的

因此，我们进行了双向两样本孟德尔随机（MR）分析，以评估初潮年龄与肌肉减少症相关特征（手握力、瘦体重、步行速度）之间的潜在因果关系。

方法

我们从 ReproGen 获得了最新的初潮年龄汇总统计数据，该研究涉及 182416 名参与者；从 EMBL 的欧洲生物信息学研究所获得了 244730 名参与者的四肢瘦体重数据；从 UK Biobank 获得了 401026 名参与者的左手握力、461089 名参与者的右手握力和 459915 名参与者的惯用步行速度数据。我们采用逆方差加权（IVW）法和其他 MR 方法来评估初潮年龄与肌肉减少症之间的双向因果关系。

结果

正向 MR 结果表明，由基因预测的初潮年龄与左手握力（IVW=0.041，P=2.00×10）、右手握力（IVW=0.053，P=1.97×10）、四肢瘦体重（IVW=0.012，P=4.38×10）和惯用步行速度（IVW=0.033，P=1.62×10）呈正相关。在反向 MR 分析中，我们还发现惯用步行速度与由基因预测的初潮年龄呈正相关（IVW=0.532，P=1.65×10）。然而，握力和四肢瘦体重与初潮年龄之间没有因果关系。