Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration.

TitleMulti-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration.
Publication TypeJournal Article
Year of Publication2019
AuthorsNoordam, R, Bos, MM, Wang, H, Winkler, TW, Bentley, AR, Kilpeläinen, TO, de Vries, PS, Sung, YJu, Schwander, K, Cade, BE, Manning, A, Aschard, H, Brown, MR, Chen, H, Franceschini, N, Musani, SK, Richard, M, Vojinovic, D, Aslibekyan, S, Bartz, TM, Fuentes, Lde Las, Feitosa, M, Horimoto, AR, Ilkov, M, Kho, M, Kraja, A, Li, C, Lim, E, Liu, Y, Mook-Kanamori, DO, Rankinen, T, Tajuddin, SM, van der Spek, A, Wang, Z, Marten, J, Laville, V, Alver, M, Evangelou, E, Graff, ME, He, M, Kühnel, B, Lyytikäinen, L-P, Marques-Vidal, P, Nolte, IM, Palmer, ND, Rauramaa, R, Shu, X-O, Snieder, H, Weiss, S, Wen, W, Yanek, LR, Adolfo, C, Ballantyne, C, Bielak, L, Biermasz, NR, Boerwinkle, E, Dimou, N, Eiriksdottir, G, Gao, C, Gharib, SA, Gottlieb, DJ, Haba-Rubio, J, Harris, TB, Heikkinen, S, Heinzer, R, Hixson, JE, Homuth, G, M Ikram, A, Komulainen, P, Krieger, JE, Lee, J, Liu, J, Lohman, KK, Luik, AI, Mägi, R, Martin, LW, Meitinger, T, Metspalu, A, Milaneschi, Y, Nalls, MA, O'Connell, J, Peters, A, Peyser, P, Raitakari, OT, Reiner, AP, Rensen, PCN, Rice, TK, Rich, SS, Roenneberg, T, Rotter, JI, Schreiner, PJ, Shikany, J, Sidney, SS, Sims, M, Sitlani, CM, Sofer, T, Strauch, K, Swertz, MA, Taylor, KD, Uitterlinden, AG, van Duijn, CM, Völzke, H, Waldenberger, M, Wallance, RB, van Dijk, KWillems, Yu, C, Zonderman, AB, Becker, DM, Elliott, P, Esko, T, Gieger, C, Grabe, HJ, Lakka, TA, Lehtimäki, T, North, KE, Penninx, BWJH, Vollenweider, P, Wagenknecht, LE, Wu, T, Xiang, Y-B, Zheng, W, Arnett, DK, Bouchard, C, Evans, MK, Gudnason, V, Kardia, S, Kelly, TN, Kritchevsky, SB, Loos, RJF, Pereira, AC, Province, M, Psaty, BM, Rotimi, C, Zhu, X, Amin, N, L Cupples, A, Fornage, M, Fox, EF, Guo, X, W Gauderman, J, Rice, K, Kooperberg, C, Munroe, PB, Liu, C-T, Morrison, AC, Rao, DC, van Heemst, D, Redline, S
JournalNat Commun
Date Published2019 Nov 12
KeywordsAdolescent, Adult, Aged, Aged, 80 and over, Chromosome Mapping, Female, Genetic Loci, Humans, Lipids, Male, Middle Aged, Phylogeny, Polymorphism, Single Nucleotide, Sleep, Young Adult

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.

Alternate JournalNat Commun
PubMed ID31719535
PubMed Central IDPMC6851116
Grant ListU01 HG007417 / HG / NHGRI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
MR/L01632X/1 / MRC_ / Medical Research Council / United Kingdom
UM1 CA173640 / CA / NCI NIH HHS / United States
MR/L01341X/1 / MRC_ / Medical Research Council / United Kingdom
R35 HL135818 / HL / NHLBI NIH HHS / United States
P30 DK020541 / DK / NIDDK NIH HHS / United States
P01 CA196569 / CA / NCI NIH HHS / United States
UM1 CA182910 / CA / NCI NIH HHS / United States
K01 HL135405 / HL / NHLBI NIH HHS / United States
R21 HL140385 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
U01 HL120393 / HL / NHLBI NIH HHS / United States
R01 DK117445 / DK / NIDDK NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01 HL118305 / HL / NHLBI NIH HHS / United States
MR/R023484/1 / MRC_ / Medical Research Council / United Kingdom
R21 HL123677 / HL / NHLBI NIH HHS / United States
S10 OD020069 / OD / NIH HHS / United States
R01 MD012765 / MD / NIMHD NIH HHS / United States

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