The EPIC-Norfolk Study
Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids.
Nature genetics 2018 ; 51: 636-648.
Bentley AR, Sung YJ, Brown MR, Winkler TW, Kraja AT, Ntalla I, Schwander K, Chasman DI, Deng X, Cheng CY, Vojinovic D, Huffman JE, Musani SK, Feitosa MF, Richard MA, Noordam R, Aschard H, Bartz TM, Ding J, Dorajoo R, Manning AK, Rankinen T, Smith AV, Tajuddin SM, Zhao W, Graff M, Alver M, Boissel M, Chai JF, Chen X, Divers J, Evangelou E, Goel A, Hagemeijer Y, Harris SE, Hartwig FP, Horimoto ARVR, Hsu FC, Hung YJ, Jackson AU, Kasturiratne A, Komulainen P, Kühnel B, Leander K, Lin KH, Luan J, Lyytikäinen LP, Matoba N, Nolte IM, Riaz M, Robino A, Said MA, Schupf N, Scott RA, Sofer T, Stančáková A, Takeuchi F, Tayo BO, van der Most PJ, Varga TV, Wang Y, Ware EB, Xiang YB, Yanek LR, Zhang W, Zhao JH, Adeyemo A, Afaq S, Amin N, Amini M, Arking DE, Aung T, Barr RG, Bielak LF, Boerwinkle E, Bottinger EP, Broeckel U, Brown M, Campbell A, Canouil M, Charumathi S, Chen YI, Christensen K, Concas MP, Connell JM, de Las Fuentes L, de Silva HJ, de Vries PS, Duan Q, Eaton CB, Eppinga RN, Faul JD, Forouhi NG, Forrester T, Friedlander Y, Gandin I, Ghanbari M, Gharib SA, Gigante B, Giulianini F, Grabe HJ, Harris TB, Heikkinen S, Heng CK, Hirata M, Hixson JE, Ikram MA, Joehanes R, Jonas JB, Justice AE, Katsuya T, Khor CC, Kilpeläinen TO, Koh WP, Kolcic I, Kooperberg C, Krieger JE, Kritchevsky SB, Kubo M, Kuusisto J, Lakka TA, Langefeld CD, Langenberg C, Launer LJ, Lehne B, Lewis CE, Liang J, Liu CT, Lohman KK, Louie T, Mägi R, Mahajan A, McKenzie CA, Meitinger T, Metspalu A, Milaneschi Y, Milani L, Mohlke KL, Momozawa Y, Morris AP, Murray AD, Nalls MA, Nauck M, Nelson CP, North KE, O'Connell JR, Palmer ND, Pedersen NL, Peters A, Peyser PA, Polasek O, Poulter N, Raitakari OT, Reiner AP, Renstrom F, Rice TK, Rich SS, Robinson JG, Rose LM, Rosendaal FR, Rudan I, Schmidt CO, Schreiner PJ, Scott WR, Sever P, Sidney S, Sims M, Smith JA, Snieder H, Starr JM, Strauch K, Stringham HM, Tan NYQ, Tang H, Taylor KD, Teo YY, Tham YC, Tiemeier H, Turner ST, Uitterlinden AG, van Heemst D, Waldenberger M, Wang H, Wang L, Wang L, Wei WB, Wilson G, Wojczynski MK, Young K, Yuan JM, Zonderman AB, Becker DM, Boehnke M, Bowden DW, Chambers JC, Cooper RS, de Faire U, Deary IJ, Elliott P, Esko T, Farrall M, Franks PW, Freedman BI, Froguel P, Gasparini P, Gieger C, Horta BL, Kamatani Y, Kato N, Kooner JS, Laakso M, Laurie CC, Lee IT, Lehtimäki T, Magnusson PKE, Oldehinkel AJ, Penninx BWJH, Pereira AC, Rauramaa R, Redline S, Samani NJ, Scott J, Shu XO, van der Harst P, Wagenknecht LE, Wang YX, Wareham NJ, Watkins H, Weir DR, Wickremasinghe AR, Zeggini E, Zheng W, Bouchard C, Evans MK, Gudnason V, Kardia SLR, Psaty BM, Ridker PM, van Dam RM, Mook-Kanamori DO, Fornage M, Province MA, Kelly TN, Fox ER, Hayward C, van Duijn CM, Tai ES, Wong TY, Loos RJF, Franceschini N, Rotter JI, Bierut LJ, Gauderman WJ, Rice K, Munroe PB, Morrison AC, Rao DC, Rotimi CN, and Cupples LA
DOI : 10.1038/s41588-019-0378-y
PubMed ID : 30926973
PMCID : PMC6467258
Abstract
The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.