Multi-ancestry analysis of gene-sleep interactions in 126,926 individuals identifies multiple novel blood lipid loci that contribute to our understanding of sleep-associated adverse blood lipid profile
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 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., 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., Duijn CMV., Völzke H., Waldenberger M., Wallance RB., Dijk KWV., Yu C., Zonderman AB., Becker DM., Elliott P., Esko T., Gieger C., Grabe HJ., Lakka TA., Lehtimäki T., Study LC., 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., Cupples LA., Fornage M., Fox EF., Guo X., Gauderman WJ., Rice K., Kooperberg C., Munroe PB., Liu C-T., Morrison AC., Rao DC., Heemst DV., Redline S.
<jats:title>Abstract</jats:title><jats:p>Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To provide new insights in the biology of sleep-associated adverse lipid profile, we conducted 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 identified 49 novel lipid loci, and 10 additional novel lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identified new gene-sleep interactions for known lipid loci such as <jats:italic>LPL</jats:italic> and <jats:italic>PCSK9</jats:italic>. The novel gene-sleep interactions had a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explained 4.25% of the variance in triglyceride concentration. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.</jats:p>