| Autor: |
Noordam R, Wang W, Nagarajan P, Wang H, Brown MR, Bentley AR, Hui Q, Kraja AT, Morrison JL, O'Connel JR, Lee S, Schwander K, Bartz TM, de las Fuentes L, Feitosa MF, Guo X, Hanfei X, Harris SE, Huang Z, Kals M, Lefevre C, Mangino M, Milaneschi Y, van der Most P, Pacheco NL, Palmer ND, Rao V, Rauramaa R, Sun Q, Tabara Y, Vojinovic D, Wang Y, Weiss S, Yang Q, Zhao W, Zhu W, Abu Yusuf Ansari M, Aschard H, Anugu P, Assimes TL, Attia J, Baker LD, Ballantyne C, Bazzano L, Boerwinkle E, Cade B, Chen HH, Chen W, Ida Chen YD, Chen Z, Cho K, De Anda-Duran I, Dimitrov L, Do A, Edwards T, Faquih T, Hingorani A, Fisher-Hoch SP, Gaziano JM, Gharib SA, Giri A, Ghanbari M, Grabe HJ, Graff M, Gu CC, He J, Heikkinen S, Hixson J, Ho YL, Hood MM, Houghton SC, Karvonen-Gutierrez CA, Kawaguchi T, Kilpeläinen TO, Komulainen P, Lin HJ, Linchangco GV, Luik AI, Ma J, Meigs JB, McCormick JB, Menni C, Nolte IM, Norris JM, Petty LE, Polikowsky HG, Raffield LM, Rich SS, Riha RL, Russ TC, Ruiz-Narvaez EA, Sitlani CM, Smith JA, Snieder H, Sofer T, Shen B, Tang J, Taylor KD, Teder-Laving M, Triatin R, Tsai MY, Völzke H, Westerman KE, Xia R, Yao J, Young KL, Zhang R, Zonderman AB, Zhu X, Below JE, Cox SR, Evans M, Fornage M, Fox ER, Franceschini N, Harlow SD, Holliday E, Ikram MA, Kelly T, Lakka TA, Lawlor DA, Li C, Liu CT, Mägi R, Manning AK, Matsuda F, Morrison AC, Nauck M, North KE, Penninx BW, Province MA, Psaty BM, Rotter JI, Spector TD, Wagenknecht LE, Willems van Dijk K, Study LC, Jaquish CE, Wilson PW, Peyser PA, Munroe PB, de Vries PS, Gauderman WJ, Sun YV, Chen H, Miller CL, Winkler TW, Rao DC, Redline S, van Heemst D |
| Jazyk: |
angličtina |
| Zdroj: |
MedRxiv : the preprint server for health sciences [medRxiv] 2024 Sep 04. Date of Electronic Publication: 2024 Sep 04. |
| DOI: |
10.1101/2024.09.02.24312466 |
| Abstrakt: |
We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify novel 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 the one-degree of freedom tests of interaction and two-degree of freedom joint tests of the main and interaction effect. In the cross-population meta-analyses, the one-degree of freedom variant-sleep interaction test identified 10 loci (P int <5.0e-9) not previously observed for lipids. Of interest, the ASPH locus (TG, LTST) is a target for aspartic and succinic acid metabolism previously shown to improve sleep and cardiovascular risk. The two-degree of freedom analyses identified an additional 7 loci that showed evidence for variant-sleep interaction (P joint <5.0e-9 in combination with P int <6.6e-6). Of these, the SLC8A1 locus (TG, STST) has been considered a potential treatment target for reduction of ischemic damage after acute myocardial infarction. Collectively, the 17 (9 with STST; 8 with LTST) loci identified in this large-scale initiative provides evidence into the biomolecular mechanisms underpinning sleep-duration-associated changes in lipid levels. The identified druggable targets may contribute to the development of novel therapies for dyslipidemia in people with sleep disturbances. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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