Title: | A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure |
Authors: | SUNG, Yun J.; WINKLER, Thomas W.; FUENTES, Lisa de las; BENTLEY, Amy R.; BROWN, Michael R.; KRAJA, Aldi T.; SCHWANDER, Karen; NTALLA, Ioanna; GUO, Xiuqing; FRANCESCHINI, Nora; LU, Yingchang; CHENG, Ching-Yu; SIM, Xueling; VOJINOVIC, Dina; MARTEN, Jonathan; MUSANI, Solomon K.; LI, Changwei; FEITOSA, Mary F.; KILPELAINEN, Tuomas O.; RICHARD, Melissa A.; NOORDAM, Raymond; ASLIBEKYAN, Stella; ASCHARD, Hugues; BARTZ, Traci M.; DORAJOO, Rajkumar; LIU, Yongmei; MANNING, Alisa K.; RANKINEN, Tuomo; SMITH, Albert Vernon; TAJUDDIN, Salman M.; TAYO, Bamidele O.; WARREN, Helen R.; ZHAO, Wei; ZHOU, Yanhua; MATOBA, Nana; SOFER, Tamar; ALVER, Maris; AMINI, Marzyeh; BOISSEL, Mathilde; CHAI, Jin Fang; CHEN, Xu; DIVERS, Jasmin; GANDIN, Ilaria; GAO, Chuan; GIULIANINI, Franco; GOEL, Anuj; HARRIS, Sarah E.; HARTWIG, Fernando Pires; HORIMOTO, Andrea R. V. R.; HSU, Fang-Chi; JACKSON, Anne U.; KAHONEN, Mika; KASTURIRATNE, Anuradhani; KUHNEL, Brigitte; LEANDER, Karin; LEE, Wen-Jane; LIN, Keng-Hung; LUAN, Jian' an; MCKENZIE, Colin A.; He Meian; NELSON, Christopher P.; RAURAMAA, Rainer; SCHUPF, Nicole; SCOTT, Robert A.; SHEU, Wayne H. H.; STANCAKOVA, Alena; TAKEUCHI, Fumihiko; MOST, Peter J. van der; VARGA, Tibor V.; WANG, Heming; WANG, Yajuan; WARE, Erin B.; WEISS, Stefan; WEN, Wanqing; YANEK, Lisa R.; ZHANG, Weihua; ZHAO, Jing Hua; AFAQ, Saima; ALFRED, Tamuno; AMIN, Najaf; ARKING, Dan; AUNG, Tin; BARR, R. Graham; BIELAK, Lawrence F.; BOERWINKLE, Eric; BOTTINGER, Erwin P.; BRAUND, Peter S.; BRODY, Jennifer A.; BROECKEL, Ulrich; CABRERA, Claudia P.; CADE, Brian; Yu Caizheng; CAMPBELL, Archie; CANOUIL, Mickael; CHAKRAVARTI, Aravinda; CHAUHAN, Ganesh; CHRISTENSEN, Kaare; COCCA, Massimiliano; COLLINS, Francis S.; CONNELL, John M.; MUTSERT, Renee de; SILVA, H. Janaka de; DEBETTE, Stephanie; DORR, Marcus; DUAN, Qing; EATON, Charles B.; EHRET, Georg; EVANGELOU, Evangelos; FAUL, Jessica D.; FISHER, Virginia A.; FOROUHI, Nita G.; FRANCO, Oscar H.; FRIEDLANDER, Yechiel; GAO, He; GIGANTE, Bruna; GRAFF, Misa; GU, C. Charles; GU, Dongfeng; GUPTA, Preeti; HAGENAARS, Saskia P.; HARRIS, Tamara B.; HE, Jiang; HEIKKINEN, Sami; HENG, Chew-Kiat; HIRATA, Makoto; HOFMAN, Albert; HOWARD, Barbara V.; HUNT, Steven; IRVIN, Marguerite R.; JIA, Yucheng; JOEHANES, Roby; JUSTICE, Anne E.; KATSUYA, Tomohiro; KAUFMAN, Joel; KERRISON, Nicola D.; KHOR, Chiea Chuen; KOH, Woon-Puay; KOISTINEN, Heikki A.; KOMULAINEN, Pirjo; KOOPERBERG, Charles; KRIEGER, Jose E.; KUBO, Michiaki; KUUSISTO, Johanna; LANGEFELD, Carl D.; LANGENBERG, Claudia; LAUNER, Lenore J.; LEHNE, Benjamin; LEWIS, Cora E.; LI, Yize; LIM, Sing Hui; LIN, Shiow; LIU, Ching-Ti; LIU, Jianjun; LIU, Jingmin; LIU, Kiang; LIU, Yeheng; LOH, Marie; LOHMAN, Kurt K.; LONG, Jirong; LOUIE, Tin; MAGI, Reedik; MAHAJAN, Anubha; MEITINGER, Thomas; METSPALU, Andres; MILANI, Lili; MOMOZAWA, Yukihide; MORRIS, Andrew P.; MOSLEY JR., Thomas H.; MUNSON, Peter; MURRAY, Alison D.; NALLS, Mike A.; NASRI, Ubaydah; NORRIS, Jill M.; NORTH, Kari; OGUNNIYI, Adesola; PADMANABHAN, Sandosh; PALMAS, Walter R.; PALMER, Nicholette D.; PANKOW, James S.; PEDERSEN, Nancy L.; PETERS, Annette; PEYSER, Patricia A.; POLASEK, Ozren; RAITAKARI, Olli T.; RENSTROM, Frida; RICE, Treva K.; RIDKER, Paul M.; ROBINO, Antonietta; ROBINSON, Jennifer G.; ROSE, Lynda M.; RUDAN, Igor; SABANAYAGAM, Charumathi; SALAKO, Babatunde L.; SANDOW, Kevin; SCHMIDT, Carsten O.; SCHREINER, Pamela J.; SCOTT, William R.; SESHADRI, Sudha; SEVER, Peter; SITLANI, Colleen M.; SMITH, Jennifer A.; SNIEDER, Harold; STARR, John M.; STRAUCH, Konstantin; TANG, Hua; TAYLOR, Kent D.; TEO, Yik Ying; THAM, Yih Chung; ULTTERLINDEN, Andre G.; WALDENBERGER, Melanie; WANG, Lihua; WANG, Ya X.; WEI, Wen Bin; WILLIAMS, Christine; WILSON, Gregory; WOJCZYNSKI, Mary K.; YAO, Jie; YUAN, Jian-Min; ZONDERMAN, Alan B.; BECKER, Diane M.; BOEHNKE, Michael; BOWDEN, Donald W.; CHAMBERS, John C.; CHEN, Yii-Der Ida; FAIRE, Ulf de; DEARY, Ian J.; ESKO, Tonu; FARRALL, Martin; FORRESTER, Terrence; FRANKS, Paul W.; FREEDMAN, Barry I.; FROGUEL, Philippe; GASPARINI, Paolo; GIEGER, Christian; HORTA, Bernardo Lessa; HUNG, Yi-Jen; JONAS, Jost B.; KATO, Norihiro; KOONER, Jaspal S.; LAAKSO, Markku; LEHTIMAKI, Terho; LIANG, Kae-Woei; MAGNUSSON, Patrik K. E.; NEWMAN, Anne B.; OLDEHINKEL, Albertine J.; PEREIRA, Alexandre C.; REDLINE, Susan; RETTIG, Rainer; SAMANI, Nilesh J.; SCOTT, James; SHU, Xiao-Ou; HARST, Pim van der; WAGENKNECHT, Lynne E.; WAREHAM, Nicholas J.; WATKINS, Hugh; WEIR, David R.; WICKREMASINGHE, Ananda R.; WU, Tangchun; ZHENG, Wei; KAMATANI, Yoichiro; LAURIE, Cathy C.; BOUCHARD, Claude; COOPER, Richard S.; EVANS, Michele K.; GUDNASON, Vilmundur; KARDIA, Sharon L. R.; KRITCHEVSKY, Stephen B.; LEVY, Daniel; O'CONNELL, Jeff R.; PSATY, Bruce M.; DAM, Rob M. van; SIMS, Mario; ARNETT, Donna K.; MOOK-KANAMORI, Dennis O.; KELLY, Tanika N.; FOX, Ervin R.; HAYWARD, Caroline; FORNAGE, Myriam; ROTIMI, Charles N.; PROVINCE, Michael A.; DUIJN, Cornelia M. van; TAI, E. Shyong; WONG, Tien Yin; LOOS, Ruth J. F.; REINER, Alex P.; ROTTER, Jerome I.; ZHU, Xiaofeng; BIERUT, Laura J.; GAUDERMAN, W. James; CAULFIELD, Mark J.; ELLIOTT, Paul; RICE, Kenneth; MUNROE, Patricia B.; MORRISON, Alanna C.; CUPPLES, L. Adrienne; RAO, Dabeeru C.; CHASMAN, Daniel I. |
Citation: | AMERICAN JOURNAL OF HUMAN GENETICS, v.102, n.3, p.375-400, 2018 |
Abstract: | Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined similar to 18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 x 10(-8)) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 x 10(-8)). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling MSRA, EBF2). |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MCP Departamento de Cardio-Pneumologia - FM/MCP Artigos e Materiais de Revistas Científicas - HC/InCor Instituto do Coração - HC/InCor Artigos e Materiais de Revistas Científicas - LIM/13 LIM/13 - Laboratório de Genética e Cardiologia Molecular Artigos e Materiais de Revistas Científicas - ODS/03 ODS/03 - Saúde e bem-estar |
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