Genome-wide gene by sleepiness interaction analysis for sleep apnea

Genetic loci reveal connections to cardiovascular risk, insulin resistance, thiamine deficiency, and resveratrol mechanism. Discovered genetic signals may offer insight into pertinent biological pathways for sleep apnea patients with an excessively sleepy subtype. Statement of Significance Sleep apnea is a complex sleep disorder. Exemplifying this is the disparately varying estimates of presence of excessive daytime sleepiness (EDS) in patients, and persistent EDS that lingers despite treatment. Some data indicate that the excessively sleepy subtype of sleep apnea carries heightened cardiovascular risk. Whether EDS influences genetic risk factors underlying sleep apnea has not yet been investigated. This study addresses this gap, as the first genome-wide gene × EDS interaction study for apnea hypopnea index, the standard sleep apnea severity metric. Genetic loci that have been previously unconsidered for sleep apnea are revealed. Discovered interaction signals highlight pathways in metabolism, genes associated with cardiometabolic traits, and therapeutic agents influencing obesity, blood pressure, oxidative stress, and apnea hypopnea index.

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Publication Details

Journal
SLEEP
Published
2025-07-24
DOI
https://doi.org/10.1093/sleep/zsaf212
Primary Topic
Obstructive Sleep Apnea Research
Type
article
Field-Weighted Citation Impact
0.00
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article

Genome-wide gene by sleepiness interaction analysis for sleep apnea

Yiyan Zhang, Megan Duff, Grace O’Brien, Brian Spitzer et al.
SLEEP
Obstructive Sleep Apnea Research
article

Genome-wide gene by sleepiness interaction analysis for sleep apnea

Yiyan Zhang, Megan Duff, Grace O’Brien, Brian Spitzer, Lynette Ekunwe, Jing Zhang, Miremad Moafi-Madani, Xiaofeng Zhu, Daniel Cohen, Hao Mei, Yamila Martínez, Han Chen, Eric Boerwinkle, Chao A. Hsiung, Michael Rueschman, Heather M. Ochs‐Balcom, Nataliia Kozhemiako, Brian E. Cade, Brendan T Keenan, Jacqueline M. Lane, Diego R. Mazzotti, Scott Heemann, Geetha Chittoor, Xihong Lin, Tamar Sofer, Nuzulul Kurniansyah, Lyle J. Palmer, Tariq Faquih, Lauren Hale, Jerome I. Rotter, Daniel J. Gottlieb, Laura M. Raffield, Matthew Maher, Noah Lorincz‐Comi, Joyita Dutta, Jiayan Liu, Susan Redline, Shaun Purcell, Pavithra Nagarajan, Kuan-Yi Hung, Nancy L. Heard‐Costa, Anne E. Justice, Kari E. North, Einat Granot‐Hershkovitz, Richa Saxena, Rebecca Montalvan, Hufeng Zhou, Shamil Sunyaev, Stephen S. Rich, Matthew Goodman, Daniel A Levy, Rachel Soemedi, Xiaofeng Zhu, Lluvia Xia, Sina A. Gharib, Diane C Lim, Bertha Hidalgo, Cynthia Tchio, Xiuqing Guo, Sanjay R. Patel, Daune Thorington, Jiwon Lee, Yiqiang Zhang, Hao Mei, Jingjing Liang, Albert V. Smith, Sutapa Mukherjee, Xiang Li, Jae Hoon Sul, Peter Y. Liu, Grace Man Zhang, Emmanuel Mignot, Bruce M. Psaty, A. J. Hirsch Allen, Faith S. Luyster, Tianyi Huang, Yushan Xu, Danielle Clarkson-Townsend, Katie L Stone, Jeff O’Connell, George T. O’Conner, Trevor Bierig, Hira Qadir
article en

Abstract

Genetic loci reveal connections to cardiovascular risk, insulin resistance, thiamine deficiency, and resveratrol mechanism. Discovered genetic signals may offer insight into pertinent biological pathways for sleep apnea patients with an excessively sleepy subtype. Statement of Significance Sleep apnea is a complex sleep disorder. Exemplifying this is the disparately varying estimates of presence of excessive daytime sleepiness (EDS) in patients, and persistent EDS that lingers despite treatment. Some data indicate that the excessively sleepy subtype of sleep apnea carries heightened cardiovascular risk. Whether EDS influences genetic risk factors underlying sleep apnea has not yet been investigated. This study addresses this gap, as the first genome-wide gene × EDS interaction study for apnea hypopnea index, the standard sleep apnea severity metric. Genetic loci that have been previously unconsidered for sleep apnea are revealed. Discovered interaction signals highlight pathways in metabolism, genes associated with cardiometabolic traits, and therapeutic agents influencing obesity, blood pressure, oxidative stress, and apnea hypopnea index.

SLEEPVol. 49(1)
Boston University (US), University of North Carolina at Chapel Hill (US), Brigham and Women's Hospital (US), National Institutes of Health (US), Alabama Department of Public Health (US), Beth Israel Deaconess Medical Center (US), Westat (United States) (US), Harvard University (US), University of Pittsburgh (US), Baylor College of Medicine (US), University of Washington (US), University of Michigan (US), UCLA Medical Center (US), VA Boston Healthcare System (US), California Pacific Medical Center (US), Australian Institute of Business (AU), Jackson Memorial Hospital (US), University of Mississippi Medical Center (US), University of Alabama at Birmingham (US), Pittsburgh Supercomputing Center (US), Massachusetts General Hospital (US), National Heart, Lung, and Blood Institute (US), Framingham Heart Study (US), Adelaide Institute for Sleep Health (AU), Australian Centre for Robotic Vision (AU), Circadian (United States) (US), Center for Pain and the Brain (US), Baylor Genetics (US), University of Virginia (US), The University of Adelaide (AU), Case Western Reserve University (US), The University of Texas Health Science Center at Houston (US)
Gender equality
Openalex Percentile: Top 76%
Obstructive Sleep Apnea Research
DOIOpen Access PDFOpenAlex
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