A1 Refereed original research article in a scientific journal
Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
Authors: de Vries P.S., Brown M.R., Bentley A.R., Sung Y.J., Winkler T.W., Ntalla I., Schwander K., Kraja A.T., Guo X., Franceschini N., Cheng C.-Y., Sim X., Vojinovic D., Huffman J.E., Musani S.K., Li C., Feitosa M.F., Richard M.A., Noordam R., Aschard H., Bartz T.M., Bielak L.F., Deng X., Dorajoo R., Lohman K.K., Manning A.K., Rankinen T., Smith A.V., Tajuddin S.M., Evangelou E., Graff M., Alver M., Boissel M., Chai J.F., Chen X., Divers J., Gandin I., Gao C., Goel A., Hagemeijer Y., Harris S.E., Hartwig F.P., He M., Horimoto A.R.V.R., Hsu F.-C., Jackson A.U., Kasturiratne A., Komulainen P., Kühnel B., Laguzzi F., Lee J.H., Luan J., Lyytikäinen L.-P., Matoba N., Nolte I.M., Pietzner M., Riaz M., Said M.A., Scott R.A., Sofer T., Stančáková A., Takeuchi F., Tayo B.O., van der Most P.J., Varga T.V., Wang Y., Ware E.B., Wen W., Yanek L.R., Zhang W., Zhao J.H., Afaq S., Amin N., Amini M., Arking D.E., Aung T., Ballantyne C., Boerwinkle E., Broeckel U., Campbell A., Canouil M., Charumathi S., Chen Y.-D.I., Connell J.M., de Faire U., de Las Fuentes L., de Mutsert R., de Silva H.J., Ding J., Dominiczak A.F., Duan Q., Eaton C.B., Eppinga R.N., Faul J.D., Fisher V., Forrester T., Franco O.H., Friedlander Y., Ghanbari M., Giulianini F., Grabe H.J., Grove M.L., Gu C.C., Harris T.B., Heikkinen S., Heng C.-K., Hirata M., Hixson J.E., Howard B.V., Ikram M.A., InterAct Consortium, Jacobs D.R., Johnson C., Jonas J.B., Kammerer C.M., Katsuya T., Khor C.C., Kilpeläinen T.O., Koh W.-P., Koistinen H.A., Kolcic I., Kooperberg C., Krieger J.E., Kritchevsky S.B., Kubo M., Kuusisto J., Lakka T.A., Langefeld C.D., Langenberg C., Launer L.J., Lehne B., Lemaitre R.N., Li Y., Liang J., Liu J., Liu K., Loh M., Louie T., Mägi R., Manichaikul A.W., McKenzie C.A., Meitinger T., Metspalu A., Milaneschi Y., Milani L., Mohlke K.L., Mosley T.H., Mukamal K.J., Nalls M.A., Nauck M., Nelson C.P., Sotoodehnia N., O'Connell J.R., Palmer N.D., Pazoki R., Pedersen N.L., Peters A., Peyser P.A., Polasek O., Poulter N., Raffel L.J., Raitakari O.T., Reiner A.P., Rice T.K., Rich S.S., Robino A., Robinson J.G., Rose L.M., Rudan I., Schmidt C.O., Schreiner P.J., Scott W.R., Sever P., Shi Y., Sidney S., Sims M., Smith B.H., Smith J.A., Snieder H., Starr J.M., Strauch K., Tan N., Taylor K.D., Teo Y.Y., Tham Y.C., Uitterlinden A.G., van Heemst D., Vuckovic D., Waldenberger M., Wang L., Wang Y., Wang Z., Wei W.B., Williams C., Wilson G., Wojczynski M.K., Yao J., Yu B., Yu C., Yuan J.-M., Zhao W., Zonderman A.B., Becker D.M., Boehnke M., Bowden D.W., Chambers J.C., Deary I.J., Esko T., Farrall M., Franks P.W., Freedman B.I., Froguel P., Gasparini P., Gieger C., Horta B.L., Kamatani Y., Kato N., Kooner J.S., Laakso M., Leander K., Lehtimäki T., Lifelines Cohort, Groningen, The Netherlands (Lifelines Cohort Study), Magnusson P.K.E., Penninx B., Pereira A.C., Rauramaa R., Samani N.J., Scott J., Shu X.-O., van der Harst P., Wagenknecht L.E., Wang Y.X., Wareham N.J., Watkins H., Weir D.R., Wickremasinghe A.R., Zheng W., Elliott P., North K.E., Bouchard C., Evans M.K., Gudnason V., Liu C.-T., Liu Y., Psaty B.M., Ridker P.M., van Dam R.M., Kardia S.L.R., Zhu X., Rotimi C.N., Mook-Kanamori D.O., Fornage M., Kelly T.N., Fox E.R., Hayward C., van Duijn C.M., Tai E.S., Wong T.Y., Liu J., Rotter J.I., Gauderman W.J., Province M.A., Munroe P.B., Rice K., Chasman D.I., Cupples L.A., Rao D.C., Morrison A.C.
Publisher: OXFORD UNIV PRESS INC
Publication year: 2019
Journal: American Journal of Epidemiology
Journal name in source: AMERICAN JOURNAL OF EPIDEMIOLOGY
Journal acronym: AM J EPIDEMIOL
Volume: 188
Issue: 6
First page : 1033
Last page: 1054
Number of pages: 22
ISSN: 0002-9262
DOI: https://doi.org/10.1093/aje/kwz005
Self-archived copy’s web address: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545280/
A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.