Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups using 1 degree of freedom (1df) interaction and 2df joint tests. Primary multi-ancestry analyses in 62,969 individuals in stage 1 identified 3 novel loci that were replicated in an additional 59,296 individuals in stage 2, including rs7955964 (FIGNL2/ANKRD33) showing significant 1df interactions with long sleep duration and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) showing significant 1df interactions with short sleep duration. Secondary ancestry-specific two-stage analyses and combined stage 1 and 2 analyses additionally identified 23 novel loci that need external replication, including 3 and 5 loci showing significant 1df interactions with long and short sleep duration, respectively. Multiple genes mapped to our 26 novel loci have known functions in sleep-wake regulation, nervous and cardiometabolic systems. We also identified new gene by long sleep interactions near five known BP loci (≤1Mb) including NME7, FAM208A, MKLN1, CEP164, and RGL3/ELAVL3. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.

中文翻译：

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多祖先的全基因组基因-睡眠相互作用确定了血压的新基因座

长时间睡眠时间短与血压升高（BP）有关，可能是通过影响神经内分泌和血管系统的分子途径的影响而引起的。为了获得对与睡眠有关的血压变异的遗传基础的新见解，我们通过短期或长期睡眠持续时间相互作用分析，对五个样本中的四个血压特征（收缩压，舒张压，平均动脉压和脉压）进行了全基因组基因分析。宗族使用1自由度（1df）交互作用和2df联合测试。在第1阶段对62,969名个体进行的主要多族裔分析确定了3个新基因座，这些新基因座在第2阶段的其他59,296个体中得到了复制 包括rs7955964（FIGNL2 / ANKRD33）显示长时间睡眠持续时间有明显的1df相互作用，而rs73493041（SNORA26 / C9orf170）和rs10406644（KCTD15 / LSM14A）显示睡眠持续时间较短有明显的1df相互作用。二级祖先特定的两阶段分析以及组合的第1阶段和第2阶段分析还确定了需要外部复制的23个新基因座，其中3个和5个基因座分别显示了长而短的睡眠时间的显着1df相互作用。映射到我们26个新基因座的多个基因在睡眠觉醒调节，神经和心脏代谢系统中具有已知功能。我们还通过长时间睡眠相互作用（包括NME7，FAM208A，MKLN1，CEP164和RGL3 / ELAVL3）在五个已知的BP基因座（≤1Mb）附近识别了新基因。