Scholarlink

<p>Frailty is a multifaceted clinical state associated with accelerated aging and adverse health outcomes. Informed etiological models of frailty hold promise for producing widespread health improvements across the aging population. Frailty is currently measured using aggregate scores, which obscure etiological pathways that are only relevant to subcomponents of frailty. Here we perform a multivariate genome-wide association study of the latent genetic architecture between 30 frailty deficits, which identifies 408 genomic risk loci. Our model includes a general factor of genetic overlap across all deficits, plus six new factors indexing a shared genetic signal across specific groups of deficits. We demonstrate the added clinical and etiological value of the six factors, including predicting frailty in external datasets, highlighting divergent genetic correlations with clinically relevant outcomes and uncovering unique underlying biology linked to aging. We show that nuanced models of frailty are key to understanding its causes and how it relates to worse health.</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

Uncovering the multivariate genetic architecture of frailty with genomic structural equation modeling

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月4日

查看全文
  • Isabelle F. Foote,
  • Jonny P. Flint,
  • Anna E. Fürtjes,
  • Jeremy M. Lawrence,
  • Donncha S. Mullin,
  • John D. Fisk,
  • Tobias K. Karakach,
  • Andrew Rutenberg,
  • Nicholas G. Martin,
  • Michelle K. Lupton,
  • David J. Llewellyn,
  • Janice M. Ranson,
  • Simon R. Cox,
  • Michelle Luciano,
  • Kenneth Rockwood,
  • Andrew D. Grotzinger

摘要

Frailty is a multifaceted clinical state associated with accelerated aging and adverse health outcomes. Informed etiological models of frailty hold promise for producing widespread health improvements across the aging population. Frailty is currently measured using aggregate scores, which obscure etiological pathways that are only relevant to subcomponents of frailty. Here we perform a multivariate genome-wide association study of the latent genetic architecture between 30 frailty deficits, which identifies 408 genomic risk loci. Our model includes a general factor of genetic overlap across all deficits, plus six new factors indexing a shared genetic signal across specific groups of deficits. We demonstrate the added clinical and etiological value of the six factors, including predicting frailty in external datasets, highlighting divergent genetic correlations with clinically relevant outcomes and uncovering unique underlying biology linked to aging. We show that nuanced models of frailty are key to understanding its causes and how it relates to worse health.