Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration
Noordam R; Bos MM; Wang H; Winkler TW; Bentley AR; Kilpeläinen TO; de Vries PS; Sung YJ; Schwander K; Cade BE; Manning A; Aschard H; Brown MR; Chen H; Franceschini N; Musani SK; Richard M; Vojinovic D; Aslibekyan S; Bartz TM; de Las Fuentes L; 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 LP; Marques-Vidal P; Nolte IM; Palmer ND; Rauramaa R; Shu XO; 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; Ikram MA; 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 KW; 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 YB; 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; Cupples LA; Fornage M; Fox EF; Guo X; Gauderman WJ; Rice K; Kooperberg C; Munroe PB; Liu CT; Morrison AC; Rao DC; van Heemst D; Redline S
https://urn.fi/URN:NBN:fi-fe2021042821137
Tiivistelmä
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.
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