- Main
Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- de Vries, Paul S;
- Brown, Michael R;
- Bentley, Amy R;
- Sung, Yun J;
- Winkler, Thomas W;
- Ntalla, Ioanna;
- Schwander, Karen;
- Kraja, Aldi T;
- Guo, Xiuqing;
- Franceschini, Nora;
- Cheng, Ching-Yu;
- Sim, Xueling;
- Vojinovic, Dina;
- Huffman, Jennifer E;
- Musani, Solomon K;
- Li, Changwei;
- Feitosa, Mary F;
- Richard, Melissa A;
- Noordam, Raymond;
- Aschard, Hugues;
- Bartz, Traci M;
- Bielak, Lawrence F;
- Deng, Xuan;
- Dorajoo, Rajkumar;
- Lohman, Kurt K;
- Manning, Alisa K;
- Rankinen, Tuomo;
- Smith, Albert V;
- Tajuddin, Salman M;
- Evangelou, Evangelos;
- Graff, Mariaelisa;
- Alver, Maris;
- Boissel, Mathilde;
- Chai, Jin Fang;
- Chen, Xu;
- Divers, Jasmin;
- Gandin, Ilaria;
- Gao, Chuan;
- Goel, Anuj;
- Hagemeijer, Yanick;
- Harris, Sarah E;
- Hartwig, Fernando P;
- He, Meian;
- Horimoto, Andrea RVR;
- Hsu, Fang-Chi;
- Jackson, Anne U;
- Kasturiratne, Anuradhani;
- Komulainen, Pirjo;
- Kühnel, Brigitte;
- Laguzzi, Federica;
- Lee, Joseph H;
- Luan, Jian'an;
- Lyytikäinen, Leo-Pekka;
- Matoba, Nana;
- Nolte, Ilja M;
- Pietzner, Maik;
- Riaz, Muhammad;
- Said, M Abdullah;
- Scott, Robert A;
- Sofer, Tamar;
- Stančáková, Alena;
- Takeuchi, Fumihiko;
- Tayo, Bamidele O;
- van der Most, Peter J;
- Varga, Tibor V;
- Wang, Yajuan;
- Ware, Erin B;
- Wen, Wanqing;
- Yanek, Lisa R;
- Zhang, Weihua;
- Zhao, Jing Hua;
- Afaq, Saima;
- Amin, Najaf;
- Amini, Marzyeh;
- Arking, Dan E;
- Aung, Tin;
- Ballantyne, Christie;
- Boerwinkle, Eric;
- Broeckel, Ulrich;
- Campbell, Archie;
- Canouil, Mickaël;
- Charumathi, Sabanayagam;
- Chen, Yii-Der Ida;
- Connell, John M;
- de Faire, Ulf;
- de las Fuentes, Lisa;
- de Mutsert, Renée;
- de Silva, H Janaka;
- Ding, Jingzhong;
- Dominiczak, Anna F;
- Duan, Qing;
- Eaton, Charles B;
- Eppinga, Ruben N;
- Faul, Jessica D;
- Fisher, Virginia;
- Forrester, Terrence;
- Franco, Oscar H;
- Friedlander, Yechiel;
- Ghanbari, Mohsen;
- Giulianini, Franco;
- Grabe, Hans J;
- Grove, Megan L;
- Gu, C Charles;
- Harris, Tamara B;
- Heikkinen, Sami;
- Heng, Chew-Kiat;
- Hirata, Makoto;
- Hixson, James E;
- Howard, Barbara V;
- Ikram, M Arfan;
- Consortium, InterAct;
- Jacobs, David R;
- Johnson, Craig;
- Jonas, Jost Bruno;
- Kammerer, Candace M;
- Katsuya, Tomohiro;
- Khor, Chiea Chuen;
- Kilpeläinen, Tuomas O;
- Koh, Woon-Puay;
- Koistinen, Heikki A;
- Kolcic, Ivana;
- Kooperberg, Charles;
- Krieger, Jose E;
- Kritchevsky, Steve B;
- Kubo, Michiaki;
- Kuusisto, Johanna;
- Lakka, Timo A;
- Langefeld, Carl D;
- Langenberg, Claudia;
- Launer, Lenore J;
- Lehne, Benjamin;
- Lemaitre, Rozenn N;
- Li, Yize;
- Liang, Jingjing;
- Liu, Jianjun;
- Liu, Kiang;
- Loh, Marie;
- Louie, Tin;
- Mägi, Reedik;
- Manichaikul, Ani W;
- McKenzie, Colin A;
- Meitinger, Thomas;
- Metspalu, Andres;
- Milaneschi, Yuri;
- Milani, Lili;
- Mohlke, Karen L;
- Mosley, Thomas H;
- Mukamal, Kenneth J;
- Nalls, Mike A;
- Nauck, Matthias;
- Nelson, Christopher P;
- Sotoodehnia, Nona;
- O'Connell, Jeff R;
- Palmer, Nicholette D;
- Pazoki, Raha;
- Pedersen, Nancy L;
- Peters, Annette;
- Peyser, Patricia A;
- Polasek, Ozren;
- Poulter, Neil;
- Raffel, Leslie J;
- Raitakari, Olli T;
- Reiner, Alex P;
- Rice, Treva K;
- Rich, Stephen S;
- Robino, Antonietta;
- Robinson, Jennifer G;
- Rose, Lynda M;
- Rudan, Igor;
- Schmidt, Carsten O;
- Schreiner, Pamela J;
- Scott, William R;
- Sever, Peter;
- Shi, Yuan;
- Sidney, Stephen;
- Sims, Mario;
- Smith, Blair H;
- Smith, Jennifer A;
- Snieder, Harold;
- Starr, John M;
- Strauch, Konstantin;
- Tan, Nicholas;
- Taylor, Kent D;
- Teo, Yik Ying;
- Tham, Yih Chung;
- Uitterlinden, André G;
- van Heemst, Diana;
- Vuckovic, Dragana;
- Waldenberger, Melanie;
- Wang, Lihua;
- Wang, Yujie;
- Wang, Zhe;
- Bin Wei, Wen;
- Williams, Christine;
- Wilson, Gregory;
- Wojczynski, Mary K;
- Yao, Jie;
- Yu, Bing;
- Yu, Caizheng;
- Yuan, Jian-Min;
- Zhao, Wei;
- Zonderman, Alan B;
- Becker, Diane M;
- Boehnke, Michael;
- Bowden, Donald W;
- Chambers, John C;
- Deary, Ian J;
- Esko, Tõnu;
- Farrall, Martin;
- Franks, Paul W;
- Freedman, Barry I;
- Froguel, Philippe;
- Gasparini, Paolo;
- Gieger, Christian;
- Horta, Bernardo L;
- Kamatani, Yoichiro;
- Kato, Norihiro;
- Kooner, Jaspal S;
- Laakso, Markku;
- Leander, Karin;
- Lehtimäki, Terho;
- Groningen, The Netherlands Lifelines Cohort;
- Magnusson, Patrik KE;
- Penninx, Brenda;
- Pereira, Alexandre C;
- Rauramaa, Rainer;
- Samani, Nilesh J;
- Scott, James;
- Shu, Xiao-Ou;
- van der Harst, Pim;
- Wagenknecht, Lynne E;
- Wang, Ya Xing;
- Wareham, Nicholas J;
- Watkins, Hugh;
- Weir, David R;
- Wickremasinghe, Ananda R;
- Zheng, Wei;
- Elliott, Paul;
- North, Kari E;
- Bouchard, Claude;
- Evans, Michele K;
- Gudnason, Vilmundur;
- Liu, Ching-Ti;
- Liu, Yongmei;
- Psaty, Bruce M;
- Ridker, Paul M;
- van Dam, Rob M;
- Kardia, Sharon LR;
- Zhu, Xiaofeng;
- Rotimi, Charles N;
- Mook-Kanamori, Dennis O;
- Fornage, Myriam;
- Kelly, Tanika N;
- Fox, Ervin R;
- Hayward, Caroline;
- van Duijn, Cornelia M;
- Tai, E Shyong;
- Wong, Tien Yin;
- Liu, Jingmin;
- Rotter, Jerome I;
- Gauderman, W James;
- Province, Michael A;
- Munroe, Patricia B;
- Rice, Kenneth;
- Chasman, Daniel I;
- Cupples, L Adrienne;
- Rao, Dabeeru C;
- Morrison, Alanna C
- et al.
Published Web Location
https://doi.org/10.1093/aje/kwz005Abstract
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 × 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 × 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.
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