Jung Jongyun, Wu Qing
Department of Biomedical Informatics, College of Medicine, The Ohio State University, Ohio, USA.
bioRxiv. 2023 May 15:2023.05.14.540743. doi: 10.1101/2023.05.14.540743.
Recent studies suggest a shared genetic architecture between muscle and bone, yet the underlying molecular mechanisms remain elusive. This study aims to identify the functionally annotated genes with shared genetic architecture between muscle and bone using the most up-to-date genome-wide association study (GWAS) summary statistics from bone mineral density (BMD) and fracture-related genetic variants. We employed an advanced statistical functional mapping method to investigate shared genetic architecture between muscle and bone, focusing on genes highly expressed in muscle tissue. Our analysis identified three genes, , , and , highly expressed in muscle tissue and previously unlinked to bone metabolism. About 90% and 85% of filtered Single-Nucleotide Polymorphisms were located in the intronic and intergenic regions for the threshold at and , respectively. was highly expressed in multiple tissues, including muscle, adrenal gland, blood vessels, and thyroid. was highly expressed in all 30 tissue types except blood, while was highly expressed in all 30 tissue types except the brain, pancreas, and skin. Our study provides a framework for using GWAS findings to highlight functional evidence of crosstalk between multiple tissues based on shared genetic architecture between muscle and bone. Further research should focus on functional validation, multi-omics data integration, gene-environment interactions, and clinical relevance in musculoskeletal disorders.
近期研究表明肌肉和骨骼之间存在共同的遗传结构,但其潜在的分子机制仍不清楚。本研究旨在利用来自骨密度(BMD)和骨折相关遗传变异的最新全基因组关联研究(GWAS)汇总统计数据,确定肌肉和骨骼之间具有共同遗传结构的功能注释基因。我们采用了一种先进的统计功能映射方法来研究肌肉和骨骼之间的共同遗传结构,重点关注在肌肉组织中高表达的基因。我们的分析确定了三个在肌肉组织中高表达且先前与骨代谢无关的基因, 、 和 。对于阈值分别为 和 的情况,约90%和85%的过滤单核苷酸多态性位于内含子和基因间区域。 在包括肌肉、肾上腺、血管和甲状腺在内的多种组织中高表达。 在除血液外的所有30种组织类型中高表达,而 在除大脑、胰腺和皮肤外的所有30种组织类型中高表达。我们的研究提供了一个框架,用于利用GWAS研究结果,基于肌肉和骨骼之间的共同遗传结构,突出多种组织间相互作用的功能证据。进一步的研究应集中在功能验证、多组学数据整合、基因-环境相互作用以及肌肉骨骼疾病的临床相关性上。
J Clin Endocrinol Metab. 2012-9-10
Front Endocrinol (Lausanne). 2022