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 R. V. R.; Hsu, Fang-Chi; Jackson, Anne U.; Kasturiratne, Anuradhani; Komulainen, Pirjo; Kühnel, Brigitte; Laguzzi, Federica; Lee, Joseph H.; Luan, Jian'an; Lyytikainen, Leo-Pekka; Matoba, Nana; Nolte, Ilja M.; Pietzner, Maik; Riaz, Muhammad; Said, M. Abdullah; Scott, Robert A.; Sofer, Tamar; Stancakova, 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, Mickael; Charumathi, Sabanayagam; Chen, Yii-Der Ida; Connell, John M.; de Faire, Ulf; de las Fuentes, Lisa; de Mutsert, Renee; 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; Jacobs, David R.; Johnson, Craig; Jonas, Jost Bruno; Kammerer, Candace M.; Katsuya, Tomohiro; Khor, Chiea Chuen; Kilpelainen, 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; Magi, 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, Andre G.; van Heemst, Diana; Vuckovic, Dragana; Waldenberger, Melanie; Wang, Lihua; Wang, Yujie; Wang, Zhe; Wei, Wen Bin; 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, Tonu; 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; Lehtimaki, Terho; Magnusson, Patrik K. E.; 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 L. R.; 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. und Morrison, Alanna C.
(2019):
Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.
In: American Journal of Epidemiology, Bd. 188, Nr. 6: S. 1033-1054
Volltext auf 'Open Access LMU' nicht verfügbar.
Abstract
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.
- Dokument bearbeiten
