Genome-wide gene-sleep interaction study identifies novel lipid loci in 732,564 participants.
Noordam Raymond, Wang Wenyi, Nagarajan Pavithra, Wang Heming, Brown Michael R, Bentley Amy R, Hui Qin, Kraja Aldi T, Morrison John L, O'Connel Jeffrey R, Lee Songmi, Schwander Karen, Bartz Traci M, de Las Fuentes Lisa, Feitosa Mary F, Guo Xiuqing, Hanfei Xu, Harris Sarah E, Huang Zhijie, Kals Mart, Lefevre Christophe, Mangino Massimo, Milaneschi Yuri, van der Most Peter J, Pacheco Natasha L, Palmer Nicholette D, Rao Varun, Rauramaa Rainer, Sun Quan, Tabara Yasuharu, Vojinovic Dina, Wang Yujie, Weiss Stefan, Yang Qian, Zhao Wei, Zhu Wanying, Ansari Md Abu Yusuf, Aschard Hugues, Anugu Pramod, Assimes Themistocles L, Attia John, Baker Laura D, Ballantyne Christie, Bazzano Lydia, Boerwinkle Eric, Cade Brain, Chen Hung-Hsin, Chen Wei, Ida Chen Yii-Der, Chen Zekai, Cho Kelly, De Anda-Duran Ileana, Dimitrov Latchezar, Do Anh, Edwards Todd, Faquih Tariq, Hingorani Aroon, Fisher-Hoch Susan P, Gaziano J Michael, Gharib Sina A, Giri Ayush, Ghanbari Mohsen, Grabe Hans Jörgen, Graff Mariaelisa, Charles Gu C, He Jiang, Heikkinen Sami, Hixson James, Ho Yuk-Lam, Hood Michelle M, Houghton Serena C, Karvonen-Gutierrez Carrie A, Kawaguchi Takahisa, Kilpeläinen Tuomas O, Komulainen Pirjo, Lin Henry J, Linchangco Gregorio V, Luik Annemarie I, Ma Jintao, Meigs James B, McCormick Joseph B, Menni Cristina, Nolte Ilja M, Norris Jill M, Petty Lauren E, Polikowsky Hannah G, Raffield Laura M, Rich Stephen S, Riha Renata L, Russ Thomas C, Ruiz-Narvaez Edward A, Sitlani Colleen M, Smith Jennifer A, Snieder Harold, Sofer Tamar, Shen Botong, Tang Jingxian, Taylor Kent D, Teder-Laving Maris, Triatin Rima, Tsai Michael Y, Völzke Henry, Westerman Kenneth E, Xia Rui, Yao Jie, Young Kristin L, Zhang Ruiyuan, Zonderman Alan B, Zhu Xiaofeng, Below Jennifer E, Cox Simon R, Evans Michelle, Fornage Myriam, Fox Ervin R, Franceschini Nora, Harlow Sioban D, Holliday Elizabeth, Ikram M Arfan, Kelly Tanika, Lakka Timo A, Lawlor Deborah A, Li Changwei, Liu Ching-Ti, Mägi Reedik, Manning Alisa K, Matsuda Fumihiko, Morrison Alanna C, Nauck Matthias, North Kari E, Penninx Brenda Wjh, Province Michael A, Psaty Bruce M, Rotter Jerome I, Spector Tim D, Wagenknecht Lynne E, van Dijk Ko Willems, Lifelines Cohort Study, Million Veteran Program, Jaquish Cashell E, Wilson Peter Wf, Peyser Patricia A, Munroe Patricia B, de Vries Paul S, Gauderman W James, Sun Yan V, Chen Han, Miller Clint L, Winkler Thomas W, Rao Dabeeru C, Redline Susan, van Heemst Diana
СтатьяМетаанализПеревод в очереди
Аннотация
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
The one-degree of freedom variant-sleep interaction test identified 10 novel loci (Pint<5.0e-9), and we additionally identify 7 loci within the two-degree of freedom analyses (Pjoint<5.0e-9 in combination with Pint<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 receptor pathway. Collectively, these findings may contribute developing novel interventions for treating dyslipidemia in people with sleep disturbances.
Для цитирования: Noordam Raymond, Wang Wenyi, Nagarajan Pavithra, Wang Heming, Brown Michael R, Bentley Amy R, Hui Qin, Kraja Aldi T, Morrison John L, O'Connel Jeffrey R, Lee Songmi, Schwander Karen, Bartz Traci M, de Las Fuentes Lisa, Feitosa Mary F, Guo Xiuqing, Hanfei Xu, Harris Sarah E, Huang Zhijie, Kals Mart, Lefevre Christophe, Mangino Massimo, Milaneschi Yuri, van der Most Peter J, Pacheco Natasha L, Palmer Nicholette D, Rao Varun, Rauramaa Rainer, Sun Quan, Tabara Yasuharu, Vojinovic Dina, Wang Yujie, Weiss Stefan, Yang Qian, Zhao Wei, Zhu Wanying, Ansari Md Abu Yusuf, Aschard Hugues, Anugu Pramod, Assimes Themistocles L, Attia John, Baker Laura D, Ballantyne Christie, Bazzano Lydia, Boerwinkle Eric, Cade Brain, Chen Hung-Hsin, Chen Wei, Ida Chen Yii-Der, Chen Zekai, Cho Kelly, De Anda-Duran Ileana, Dimitrov Latchezar, Do Anh, Edwards Todd, Faquih Tariq, Hingorani Aroon, Fisher-Hoch Susan P, Gaziano J Michael, Gharib Sina A, Giri Ayush, Ghanbari Mohsen, Grabe Hans Jörgen, Graff Mariaelisa, Charles Gu C, He Jiang, Heikkinen Sami, Hixson James, Ho Yuk-Lam, Hood Michelle M, Houghton Serena C, Karvonen-Gutierrez Carrie A, Kawaguchi Takahisa, Kilpeläinen Tuomas O, Komulainen Pirjo, Lin Henry J, Linchangco Gregorio V, Luik Annemarie I, Ma Jintao, Meigs James B, McCormick Joseph B, Menni Cristina, Nolte Ilja M, Norris Jill M, Petty Lauren E, Polikowsky Hannah G, Raffield Laura M, Rich Stephen S, Riha Renata L, Russ Thomas C, Ruiz-Narvaez Edward A, Sitlani Colleen M, Smith Jennifer A, Snieder Harold, Sofer Tamar, Shen Botong, Tang Jingxian, Taylor Kent D, Teder-Laving Maris, Triatin Rima, Tsai Michael Y, Völzke Henry, Westerman Kenneth E, Xia Rui, Yao Jie, Young Kristin L, Zhang Ruiyuan, Zonderman Alan B, Zhu Xiaofeng, Below Jennifer E, Cox Simon R, Evans Michelle, Fornage Myriam, Fox Ervin R, Franceschini Nora, Harlow Sioban D, Holliday Elizabeth, Ikram M Arfan, Kelly Tanika, Lakka Timo A, Lawlor Deborah A, Li Changwei, Liu Ching-Ti, Mägi Reedik, Manning Alisa K, Matsuda Fumihiko, Morrison Alanna C, Nauck Matthias, North Kari E, Penninx Brenda Wjh, Province Michael A, Psaty Bruce M, Rotter Jerome I, Spector Tim D, Wagenknecht Lynne E, van Dijk Ko Willems, Lifelines Cohort Study, Million Veteran Program, Jaquish Cashell E, Wilson Peter Wf, Peyser Patricia A, Munroe Patricia B, de Vries Paul S, Gauderman W James, Sun Yan V, Chen Han, Miller Clint L, Winkler Thomas W, Rao Dabeeru C, Redline Susan, van Heemst Diana. Genome-wide gene-sleep interaction study identifies novel lipid loci in 732,564 participants.. Atherosclerosis. 2025. DOI: 10.1016/j.atherosclerosis.2025.120603.
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