Citation: American Journal of Epidemiology. 2019 Jan 29.Journal: American journal of epidemiology.Published: ; 2019ISSN: 0002-9262.Full author list: de Vries PS; Brown MR; Bentley AR; Sung YJ; Winkler TW; Ntalla I; Schwander K; Kraja AT; Guo X; Franceschini N; Cheng CY; Sim X; Vojinovic D; Huffman JE; Musani SK; Li C; Feitosa MF; Richard MA; Noordam R; Aschard H; Bartz TM; Bielak LF; Deng X; Dorajoo R; Lohman KK; Manning AK; Rankinen T; Smith AV; Tajuddin SM; Evangelou E; Graff M; Alver M; Boissel M; Chai JF; Chen X; Divers J; Gandin I; Gao C; Goel A; Hagemeijer Y; Harris SE; Hartwig FP; He M; Horimoto ARVR; Hsu FC; Jackson AU; Kasturiratne A; Komulainen P; Kuhnel B; Laguzzi F; Lee JH; Luan J; Lyytikainen LP; Matoba N; Nolte IM; Pietzner M; Riaz M; Said MA; Scott RA; Sofer T; Stancakova A; Takeuchi F; Tayo BO; van der Most PJ; Varga TV; Wang Y; Ware EB; Wen W; Yanek LR; Zhang W; Zhao JH; Afaq S; Amin N; Amini M; Arking DE; Aung T; Ballantyne C; Boerwinkle E; Broeckel U; Campbell A; Canouil M; Charumathi S; Chen YI; Connell JM; de Faire U; de Las Fuentes L; de Mutsert R; de Silva HJ; Ding J; Dominiczak AF; Duan Q; Eaton CB; Eppinga RN; Faul JD; Fisher V; Forrester T; Franco OH; Friedlander Y; Ghanbari M; Giulianini F; Grabe HJ; Grove ML; Gu CC; Harris TB; Heikkinen S; Heng CK; Hirata M; Hixson JE; Howard BV; Ikram MA; InterAct Consortium; Jacobs DR Jr; Johnson C; Jonas JB; Kammerer CM; Katsuya T; Khor CC; Kilpelainen TO; Koh WP; Koistinen HA; Kolcic I; Kooperberg C; Krieger JE; Kritchevsky SB; Kubo M; Kuusisto J; Lakka TA; Langefeld CD; Langenberg C; Launer LJ; Lehne B; Lemaitre RN; Li Y; Liang J; Liu J; Liu K; Loh M; Louie T; Magi R; Manichaikul AW; McKenzie CA; Meitinger T; Metspalu A; Milaneschi Y; Milani L; Mohlke KL; Mosley TH Jr; Mukamal KJ; Nalls MA; Nauck M; Nelson CP; Sotoodehnia N; O'Connell JR; Palmer ND; Pazoki R; Pedersen NL; Peters A; Peyser PA; Polasek O; Poulter N; Raffel LJ; Raitakari OT; Reiner AP; Rice TK; Rich SS; Robino A; Robinson JG; Rose LM; Rudan I; Schmidt CO; Schreiner PJ; Scott WR; Sever P; Shi Y; Sidney S; Sims M; Smith BH; Smith JA; Snieder H; Starr JM; Strauch K; Tan N; Taylor KD; Teo YY; Tham YC; Uitterlinden AG; van Heemst D; Vuckovic D; Waldenberger M; Wang L; Wang Y; Wang Z; Wei WB; Williams C; Wilson G Sr; Wojczynski MK; Yao J; Yu B; Yu C; Yuan JM; Zhao W; Zonderman AB; Becker DM; Boehnke M; Bowden DW; Chambers JC; Deary IJ; Esko T; Farrall M; Franks PW; Freedman BI; Froguel P; Gasparini P; Gieger C; Horta BL; Kamatani Y; Kato N; Kooner JS; Laakso M; Leander K; Lehtimaki T; Lifelines Cohort, Groningen, The Netherlands (Lifelines Cohort Study); Magnusson PKE; Penninx B; Pereira AC; Rauramaa R; Samani NJ; Scott J; Shu XO; van der Harst P; Wagenknecht LE; Wang YX; Wareham NJ; Watkins H; Weir DR; Wickremasinghe AR; Zheng W; Elliott P; North KE; Bouchard C; Evans MK; Gudnason V; Liu CT; Liu Y; Psaty BM; Ridker PM; van Dam RM; Kardia SLR; Zhu X; Rotimi CN; Mook-Kanamori DO; Fornage M; Kelly TN; Fox ER; Hayward C; van Duijn CM; Tai ES; Wong TY; Liu J; Rotter JI; Gauderman WJ; Province MA; Munroe PB; Rice K; Chasman DI; Cupples LA; Rao DC; Morrison AC.UI/PMID: 30698716.Subject(s): IN PROCESS -- NOT YET INDEXEDInstitution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline article type(s): Journal ArticleDigital Object Identifier: https://dx.doi.org/10.1093/aje/kwz005 (Click here)Abbreviated citation: Am J Epidemiol. 2019 Jan 29.Local Holdings: Available online from MWHC library: 1996 - present, Available in print through MWHC library: 1996 - 2006.Abstract: An individual'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 multi-ancestry 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 five ancestry groups. Genetic main and interaction effects were jointly assessed by 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 Stage 1 and Stage 2, 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 (PCSK5, VEGFB, and A1CF) with a putative role in lipid metabolism based on existing evidence from cellular and experimental models.