Genome-wide gene-sleep interaction study identifies novel lipid loci in 732,564 participants

作者：Raymond Noordam, Wenyi Wang, Pavithra Nagarajan, Heming Wang, Michael R. Brown, Amy R. Bentley, Qin Hui, Aldi T. Kraja, John L. Morrison, Jeffrey R. O’Connel, Songmi Lee, Karen Schwander, Traci M. Bartz, Lisa de las Fuentes, Mary F. Feitosa, Xiuqing Guo, Xu Hanfei, Sarah E. Harris, Zhijie Huang, Mart Kals, Christophe Lefèvre, Massimo Mangino, Yuri Milaneschi, Peter J. van der Most, Natasha L. Pacheco, Nicholette D. Palmer, Varun Rao, Rainer Rauramaa, Quan Sun, Yasuharu Tabara, Dina Vojinović, Yujie Wang, Stefan Weiß, Qian Yang, Wei Zhao, Wanying Zhu, Md Abu Yusuf Ansari, Hugues Aschard, Pramod Anugu, Themistocles L. Assimes, John Attia, Laura D. Baker, Christie M. Ballantyne, Lydia Bazzano, Eric Boerwinkle, Brain Cade, Hung‐Hsin Chen, Wei Chen, Yii-Der Ida Chen, Zekai Chen, Kelly Cho, Ileana De Anda‐Duran, Latchezar Dimitrov, Anh Do, Todd L. Edwards, Tariq Faquih, Aroon D. Hingorani, Susan P. Fisher‐Hoch, J. Michael Gaziano, Sina A. Gharib, Ayush Giri, Mohsen Ghanbari, Hans J. Grabe, Mariaelisa Graff, C. Charles Gu, Jiang He, Sami Heikkinen, James E. Hixson, Yuk‐Lam Ho, Michelle M. Hood, Serena C. Houghton, Carrie Karvonen‐Gutierrez, Takahisa Kawaguchi, Tuomas O. Kilpeläinen, Pirjo Komulainen, Henry J. Lin, Gregorio V. Linchangco, Annemarie I. Luik, Jintao Ma, James B. Meigs, Joseph B. McCormick, Cristina Menni, Ilja M. Nolte, Jill M. Norris, Lauren E. Petty, Hannah G. Polikowsky, Laura M. Raffield, Stephen S. Rich, Renata L. Riha, Thomas C Russ, Edward Ruiz-Narváez, Colleen M. Sitlani, Jennifer A. Smith, Harold Snieder, Tamar Sofer, Botong Shen, Jingxian Tang, Kent D. Taylor, Maris Teder‐Laving, Rima Destya Triatin, Michael Y. Tsai, Henry Völzke, Kenneth E. Westerman, Rui Xia, Jie Yao, Kristin L. Young, Ruiyuan Zhang, Alan B Zonderman, Xiaofeng Zhu, Jennifer E. Below, Simon R. Cox, Michelle Evans, Myriam Fornage, Ervin R. Fox, Nora Franceschini, Sioḃán D. Harlow, Elizabeth Holliday, M. Arfan Ikram, Tanika N. Kelly, Timo A Lakka, Deborah A. Lawlor, Changwei Li, Ching‐Ti Liu, Reedik Mägi, Alisa K. Manning, Fumihiko Matsuda, Alanna C. Morrison, Matthias Nauck, Kari E. North, Brenda W.J.H. Penninx, Michael A. Province, Bruce M. Psaty, Jerome I. Rotter, Tim D. Spector, Lynne E. Wagenknecht, Ko Willems van Dijk, Cashell E. Jaquish, Peter W.F. Wilson, Patricia A. Peyser, Patricia B. Munroe, Paul S. de Vries, W. James Gauderman, Yan V. Sun, Han Chen, Clint L. Miller, Thomas Winkler, D. C. Rao, Susan Redline, Diana van Heemst · 发表于：Atherosclerosis · 年份：2025 · DOI：10.1016/j.atherosclerosis.2025.120603 · 被引用次数：2 · 研究领域：Sleep and related disorders、Sleep and Wakefulness Research、Obstructive Sleep Apnea Research

BACKGROUND AND AIMS: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets. METHODS: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) total sleep time were defined by the extreme 20 % of the age- and sex-standardized values within each cohort. Based on cohort-level summary statistics data, we performed meta-analyses for one-degree of freedom tests of interaction and two-degree of freedom joint tests of the SNP-main and -interaction effect on lipid levels. RESULTS: <6.6e-6). Multiple loci, including those mapped to APSH (target for aspartic and succinic acid) and SLC8A1 showed biological plausibility and druggability potential based on literature. CONCLUSIONS: Collectively, the 17 (9 with short and 8 with long sleep) loci provided evidence into the biomolecular mechanisms underlying sleep-associated lipid changes, including potential involvement of the vitamin D re...