Scholarlink

<p>Gene–environment interaction (G×E) analyses play a crucial role in advancing genetic discovery, addressing missing heritability, and facilitating precision medicine. However, existing G×E methods are mostly designed for cross-sectional data, limiting the utility of longitudinal data. Here we propose SAGELD, a scalable and accurate genome-wide G×E method for longitudinal traits that controls for sample relatedness in large-scale datasets. SAGELD uses matrix projection to construct test statistics and the SPA<sub>GRM</sub> framework to efficiently control for sample relatedness, achieving 10- to 10,000-fold speedups over existing methods while maintaining greater power than cross-sectional analyses. We evaluated SAGELD through extensive simulations and UK Biobank analyses. Using age and body mass index as environmental exposures, we identified 74 loci with genetic × age interactions and 5 loci with genetic × adiposity interactions in the pooled analysis of longitudinal primary care data and cross-sectional assessment data. These results highlight the advantages of leveraging longitudinal data in G×E analyses.</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

Leveraging longitudinal data to boost statistical power for gene–environment interaction analysis

  • 期刊论文

  • 发表日期：

    2026年6月16日

查看全文
  • He Xu,
  • Yuzhuo Ma,
  • Yufei Liu,
  • Yin Li,
  • Lin Wan,
  • Ji-Feng Zhang,
  • Yanlong Zhao,
  • Weihua Yue,
  • Peipei Zhang,
  • Wenjian Bi

摘要

Gene–environment interaction (G×E) analyses play a crucial role in advancing genetic discovery, addressing missing heritability, and facilitating precision medicine. However, existing G×E methods are mostly designed for cross-sectional data, limiting the utility of longitudinal data. Here we propose SAGELD, a scalable and accurate genome-wide G×E method for longitudinal traits that controls for sample relatedness in large-scale datasets. SAGELD uses matrix projection to construct test statistics and the SPAGRM framework to efficiently control for sample relatedness, achieving 10- to 10,000-fold speedups over existing methods while maintaining greater power than cross-sectional analyses. We evaluated SAGELD through extensive simulations and UK Biobank analyses. Using age and body mass index as environmental exposures, we identified 74 loci with genetic × age interactions and 5 loci with genetic × adiposity interactions in the pooled analysis of longitudinal primary care data and cross-sectional assessment data. These results highlight the advantages of leveraging longitudinal data in G×E analyses.