Scholarlink

<p>Sleep is essential for health and regulated by genetic and environmental factors. We perform genome-wide association studies of device-measured sleep duration, efficiency, and accelerometer-derived rapid eye movement (REM) and non-rapid eye movement (NREM) sleep in 80,013 UK Biobank participants. We identify 20 autosomal loci, 12 of which have not been previously reported, including genome-wide significant associations for REM and NREM sleep duration. <i>MEIS1</i> shows strong opposing effects on REM and NREM durations and is intolerant to loss-of-function mutations, suggesting an essential role in the regulation of REM/NREM sleep balance. Functional enrichment analysis identifies statistically significant pathways related to chromatin remodelling, lipid metabolism, and metal ion homeostasis while tissue enrichment analysis highlights significant signals in the hypothalamus and frontal cortex. Sex-stratified analyses identify distinct loci, including <i>FOXP2</i> and <i>NRXN3</i> in females and <i>LRP1B</i>, <i>NPBWR2</i>, and <i>PABPC4</i> in males. Mendelian randomization supports associations between shorter sleep duration and higher cardiometabolic risk. These findings highlight sex- and phase-specific regulators of human sleep architecture, providing biological insights and potential therapeutic targets.</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

Genetic architecture of sleep in a genome wide association study of device measured sleep traits

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月1日

查看全文
  • Laura Portas,
  • Hang Yuan,
  • Lina Cai,
  • Karl Smith-Byrne,
  • Stefan van Duijvenboden,
  • Simon D. Kyle,
  • David Ray,
  • Joanna MM Howson,
  • Aiden Doherty

摘要

Sleep is essential for health and regulated by genetic and environmental factors. We perform genome-wide association studies of device-measured sleep duration, efficiency, and accelerometer-derived rapid eye movement (REM) and non-rapid eye movement (NREM) sleep in 80,013 UK Biobank participants. We identify 20 autosomal loci, 12 of which have not been previously reported, including genome-wide significant associations for REM and NREM sleep duration. MEIS1 shows strong opposing effects on REM and NREM durations and is intolerant to loss-of-function mutations, suggesting an essential role in the regulation of REM/NREM sleep balance. Functional enrichment analysis identifies statistically significant pathways related to chromatin remodelling, lipid metabolism, and metal ion homeostasis while tissue enrichment analysis highlights significant signals in the hypothalamus and frontal cortex. Sex-stratified analyses identify distinct loci, including FOXP2 and NRXN3 in females and LRP1B, NPBWR2, and PABPC4 in males. Mendelian randomization supports associations between shorter sleep duration and higher cardiometabolic risk. These findings highlight sex- and phase-specific regulators of human sleep architecture, providing biological insights and potential therapeutic targets.