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@ARTICLE{Noordam:282910,
author = {Noordam, Raymond and Wang, Wenyi and Nagarajan, Pavithra
and Wang, Heming and Brown, Michael R and Bentley, Amy R and
Hui, Qin and Kraja, Aldi T and Morrison, John L and
O'Connel, Jeffrey R and Lee, Songmi and Schwander, Karen and
Bartz, Traci M and de Las Fuentes, Lisa and Feitosa, Mary F
and Guo, Xiuqing and Hanfei, Xu and Harris, Sarah E and
Huang, Zhijie and Kals, Mart and Lefevre, Christophe and
Mangino, Massimo and Milaneschi, Yuri and van der Most,
Peter J and Pacheco, Natasha L and Palmer, Nicholette D and
Rao, Varun and Rauramaa, Rainer and Sun, Quan and Tabara,
Yasuharu and Vojinovic, Dina and Wang, Yujie and Weiss,
Stefan and Yang, Qian and Zhao, Wei and Zhu, Wanying and
Ansari, Md Abu Yusuf and Aschard, Hugues and Anugu, Pramod
and Assimes, Themistocles L and Attia, John and Baker, Laura
D and Ballantyne, Christie and Bazzano, Lydia and
Boerwinkle, Eric and Cade, Brain and Chen, Hung-Hsin and
Chen, Wei and Ida Chen, Yii-Der and Chen, Zekai and Cho,
Kelly and De Anda-Duran, Ileana and Dimitrov, Latchezar and
Do, Anh and Edwards, Todd and Faquih, Tariq and Hingorani,
Aroon and Fisher-Hoch, Susan P and Gaziano, J Michael and
Gharib, Sina A and Giri, Ayush and Ghanbari, Mohsen and
Grabe, Hans Jörgen and Graff, Mariaelisa and Charles Gu, C.
and He, Jiang and Heikkinen, Sami and Hixson, James and Ho,
Yuk-Lam and Hood, Michelle M and Houghton, Serena C and
Karvonen-Gutierrez, Carrie A and Kawaguchi, Takahisa and
Kilpeläinen, Tuomas O and Komulainen, Pirjo and Lin, Henry
J and Linchangco, Gregorio V and Luik, Annemarie I and Ma,
Jintao and Meigs, James B and McCormick, Joseph B and Menni,
Cristina and Nolte, Ilja M and Norris, Jill M and Petty,
Lauren E and Polikowsky, Hannah G and Raffield, Laura M and
Rich, Stephen S and Riha, Renata L and Russ, Thomas C and
Ruiz-Narvaez, Edward A and Sitlani, Colleen M and Smith,
Jennifer A and Snieder, Harold and Sofer, Tamar and Shen,
Botong and Tang, Jingxian and Taylor, Kent D and
Teder-Laving, Maris and Triatin, Rima and Tsai, Michael Y
and Völzke, Henry and Westerman, Kenneth E and Xia, Rui and
Yao, Jie and Young, Kristin L and Zhang, Ruiyuan and
Zonderman, Alan B and Zhu, Xiaofeng and Below, Jennifer E
and Cox, Simon R and Evans, Michelle and Fornage, Myriam and
Fox, Ervin R and Franceschini, Nora and Harlow, Sioban D and
Holliday, Elizabeth and Ikram, M Arfan and Kelly, Tanika and
Lakka, Timo A and Lawlor, Deborah A and Li, Changwei and
Liu, Ching-Ti and Mägi, Reedik and Manning, Alisa K and
Matsuda, Fumihiko and Morrison, Alanna C and Nauck, Matthias
and North, Kari E and Penninx, Brenda Wjh and Province,
Michael A and Psaty, Bruce M and Rotter, Jerome I and
Spector, Tim D and Wagenknecht, Lynne E and van Dijk, Ko
Willems and Jaquish, Cashell E and Wilson, Peter Wf and
Peyser, Patricia A and Munroe, Patricia B and de Vries, Paul
S and Gauderman, W James and Sun, Yan V and Chen, Han and
Miller, Clint L and Winkler, Thomas W and Rao, Dabeeru C and
Redline, Susan and van Heemst, Diana},
collaboration = {Study, Lifelines Cohort and Program, Million Veteran},
title = {{G}enome-wide gene-sleep interaction study identifies novel
lipid loci in 732,564 participants.},
journal = {Atherosclerosis},
volume = {412},
issn = {0021-9150},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DZNE-2025-01371},
pages = {120603},
year = {2026},
abstract = {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.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.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.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.},
keywords = {Humans / Genome-Wide Association Study / Male / Female /
Sleep: genetics / Polymorphism, Single Nucleotide / Middle
Aged / Dyslipidemias: genetics / Dyslipidemias: blood /
Dyslipidemias: diagnosis / Genetic Predisposition to Disease
/ Triglycerides: blood / Lipids: blood / Adult / Aged /
Genetic Loci / Phenotype / Cholesterol, LDL: blood /
Cholesterol, HDL: blood / Biomarkers: blood / Sleep Wake
Disorders: genetics / Sleep Wake Disorders: blood / Sleep
Wake Disorders: physiopathology / Triglycerides (NLM
Chemicals) / Lipids (NLM Chemicals) / Cholesterol, LDL (NLM
Chemicals) / Cholesterol, HDL (NLM Chemicals) / Biomarkers
(NLM Chemicals)},
cin = {AG Grabe},
ddc = {610},
cid = {I:(DE-2719)5000001},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41325697},
doi = {10.1016/j.atherosclerosis.2025.120603},
url = {https://pub.dzne.de/record/282910},
}