Scholarlink

<p>Metabolites in plasma form biosignatures of a range of common complex human diseases. Discovering variants with pleiotropic effects across metabolites can reveal underlying biological mechanisms. We therefore performed uni- and multivariate genome-wide association studies (GWAS) on 249 circulating metabolic markers across 328,006 UK Biobank and Estonian Biobank participants. We investigated rare variation through whole exome sequencing gene burden tests, analysed the role of body mass index through Mendelian randomization, and performed genome-wide interaction analyses with sex. We discovered 15,585 loci summed over the univariate GWAS, with high pleiotropy across markers, linked to a wide range of disorders. Findings from common and rare variant gene tests converged on lipid homeostasis pathways. 31 loci interacted with sex, mapped to genes involved in cholesterol processing. The findings offer insights into the genetic architecture of circulating metabolites, revealing pleiotropic loci, highlighting the role of rare variation, and uncovering sex-specific molecular mechanisms of lipid metabolism.</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

Pleiotropic and sex-specific genetic mechanisms of circulating metabolic markers

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月28日

查看全文
  • Dennis van der Meer,
  • Zillur Rahman,
  • Aigar Ottas,
  • Pravesh Parekh,
  • Gleda Kutrolli,
  • Sara E. Stinson,
  • Maria Koromina,
  • Jaroslav Rokicki,
  • Ida E. Sønderby,
  • Nadine Parker,
  • Markos Tesfaye,
  • Guy Hindley,
  • Linn N. Rødevand,
  • Elise Koch,
  • Andres Metspalu,
  • Tõnu Esko,
  • Reedik Mägi,
  • Mait Metspalu,
  • Mari Nelis,
  • Georgi Hudjashov,
  • Priit Palta,
  • Nele Taba,
  • Erik Abner,
  • Jaanika Kronberg,
  • Urmo Võsa,
  • Nils Eiel Steen,
  • Jens Petter Berg,
  • Kevin S. O’Connell,
  • Olav B. Smeland,
  • Oleksandr Frei,
  • Anders M. Dale,
  • Srdjan Djurovic,
  • Kelli Lehto,
  • Maris Alver,
  • Lili Milani,
  • Alexey A. Shadrin,
  • Ole A. Andreassen

摘要

Metabolites in plasma form biosignatures of a range of common complex human diseases. Discovering variants with pleiotropic effects across metabolites can reveal underlying biological mechanisms. We therefore performed uni- and multivariate genome-wide association studies (GWAS) on 249 circulating metabolic markers across 328,006 UK Biobank and Estonian Biobank participants. We investigated rare variation through whole exome sequencing gene burden tests, analysed the role of body mass index through Mendelian randomization, and performed genome-wide interaction analyses with sex. We discovered 15,585 loci summed over the univariate GWAS, with high pleiotropy across markers, linked to a wide range of disorders. Findings from common and rare variant gene tests converged on lipid homeostasis pathways. 31 loci interacted with sex, mapped to genes involved in cholesterol processing. The findings offer insights into the genetic architecture of circulating metabolites, revealing pleiotropic loci, highlighting the role of rare variation, and uncovering sex-specific molecular mechanisms of lipid metabolism.