Scholarlink

Purpose of review <p>While GWAS has identified many loci associated with bone mineral density (BMD), translating these findings into functional insights and treatments remains challenging. Post-GWAS methods such as Transcriptome-Wide Association Study (TWAS), Phenome-Wide Association Study (PheWAS), and Mendelian Randomization (MR) provide complementary strategies to prioritize genes and causal risk factors. This review summarizes findings from these studies.</p> Recent Findings <p>TWASs have identified many potential causal genes for BMD, but only a few, such as PPP6R3, have been confirmed through functional validation. Several MR studies have provided increasing evidence of causal relationships between inflammatory bowel disease, NAFLD, COPD, and lower BMD, along with a higher risk of osteoporosis. PheWAS and MR also identify bone marrow fat as a risk factor for decreased BMD.</p> Summary <p>It is essential to bridge the critical gap between statistical discovery and biological validation. Moreover, the lack of bone-specific transcriptomic data remains a significant limitation, underscoring the need to generate such datasets. At the same time, all MR evidence should be corroborated with other sources to strengthen causal conclusions.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

PHEWAS, TWAS, Mendelian Randomization in Osteoporosis Research: the good, the bad, and the ugly

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月10日

查看全文
  • Siwen Li,
  • Katerina Trajanoska

摘要

Purpose of review

While GWAS has identified many loci associated with bone mineral density (BMD), translating these findings into functional insights and treatments remains challenging. Post-GWAS methods such as Transcriptome-Wide Association Study (TWAS), Phenome-Wide Association Study (PheWAS), and Mendelian Randomization (MR) provide complementary strategies to prioritize genes and causal risk factors. This review summarizes findings from these studies.

Recent Findings

TWASs have identified many potential causal genes for BMD, but only a few, such as PPP6R3, have been confirmed through functional validation. Several MR studies have provided increasing evidence of causal relationships between inflammatory bowel disease, NAFLD, COPD, and lower BMD, along with a higher risk of osteoporosis. PheWAS and MR also identify bone marrow fat as a risk factor for decreased BMD.

Summary

It is essential to bridge the critical gap between statistical discovery and biological validation. Moreover, the lack of bone-specific transcriptomic data remains a significant limitation, underscoring the need to generate such datasets. At the same time, all MR evidence should be corroborated with other sources to strengthen causal conclusions.