A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Publication

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Journal Paper/Review - Feb 15, 2018

Bowden Donald W, Snieder Harold, Smith Jennifer A, Sitlani Colleen M, Sever Peter, Seshadri Sudha, Scott William R, Schreiner Pamela J, Schmidt Carsten O, Sandow Kevin, Salako Babatunde L, Sabanayagam Charumathi, Rudan Igor, Rose Lynda M, Robinson Jennifer G, Robino Antonietta, Ridker Paul M, Starr John M, Strauch Konstantin, Tang Hua, Boehnke Michael, Becker Diane M, Zonderman Alan B, Yuan Jian-Min, Yao Jie, Wojczynski Mary K, Wilson Gregory, Williams Christine, Wei Wen Bin, Wang Ya X, Wang Lihua, Waldenberger Melanie, Uitterlinden André G, Tham Yih Chung, Teo Yik Ying, Taylor Kent D, Rice Treva K, Renström Frida, Raitakari Olli T, Metspalu Andres, Meitinger Thomas, Mahajan Anubha, Mägi Reedik, Louie Tin, Long Jirong, Lohman Kurt K, Loh Marie, Liu Yeheng, Liu Kiang, Liu Jingmin, Liu Jianjun, Liu Ching-Ti, Lin Shiow, Lim Sing Hui, Lifelines Cohort Study, Milani Lili, Momozawa Yukihide, Morris Andrew P, Polasek Ozren, Peyser Patricia A, Peters Annette, Pedersen Nancy L, Pankow James S, Palmer Nicholette D, Palmas Walter R, Padmanabhan Sandosh, Ogunniyi Adesola, North Kari, Norris Jill M, Nasri Ubaydah, Nalls Mike A, Murray Alison D, Munson Peter, Mosley Thomas H, Li Yize, Chasman Daniel I, Hayward Caroline, Fox Ervin R, Kelly Tanika N, Mook-Kanamori Dennis O, Arnett Donna K, Sims Mario, van Dam Rob M, Psaty Bruce M, O'Connell Jeff R, Levy Daniel, Kritchevsky Stephen B, Kardia Sharon L R, Gudnason Vilmundur, Evans Michele K, Cooper Richard S, Bouchard Claude, Fornage Myriam, Rotimi Charles N, Province Michael A, Rao Dabeeru C, Cupples L Adrienne, Morrison Alanna C, Munroe Patricia B, Rice Kenneth, Elliott Paul, Caulfield Mark J, Gauderman W James, Bierut Laura J, Zhu Xiaofeng, Rotter Jerome I, Reiner Alex P, Loos Ruth J F, Wong Tien Yin, Tai E Shyong, van Duijn Cornelia M, Laurie Cathy C, Kamatani Yoichiro, Zheng Wei, Kooner Jaspal S, Kato Norihiro, Jonas Jost B, Hung Yi-Jen, Horta Bernardo Lessa, Gieger Christian, Gasparini Paolo, Froguel Philippe, Freedman Barry I, Franks Paul W, Forrester Terrence, Farrall Martin, Esko Tõnu, Deary Ian J, de Faire Ulf, Chen Yii-Der Ida, Laakso Markku, Lehtimäki Terho, Liang Kae-Woei, Wu Tangchun, Wickremasinghe Ananda R, Weir David R, Watkins Hugh, Wareham Nicholas J, Wagenknecht Lynne E, van der Harst Pim, Shu Xiao-Ou, Scott James, Samani Nilesh J, Rettig Rainer, Redline Susan, Pereira Alexandre C, Oldehinkel Albertine J, Newman Anne B, Magnusson Patrik K E, Chambers John C, Lewis Cora E, Yanek Lisa R, Leander Karin, Kühnel Brigitte, Kasturiratne Anuradhani, Kähönen Mika, Jackson Anne U, Hsu Fang-Chi, Horimoto Andrea R V R, Hartwig Fernando Pires, Harris Sarah E, Goel Anuj, Giulianini Franco, Gao Chuan, Gandin Ilaria, Divers Jasmin, Chen Xu, Chai Jin Fang, Lee Wen-Jane, Lin Keng-Hung, 'an Luan Jian, Wen Wanqing, Weiss Stefan, Ware Erin B, Wang Yajuan, Wang Heming, Varga Tibor V, van der Most Peter J, Takeuchi Fumihiko, Stančáková Alena, Sheu Wayne H H, Scott Robert A, Schupf Nicole, Rauramaa Rainer, Nelson Christopher P, He Meian, McKenzie Colin A, Boissel Mathilde, Amini Marzyeh, Alver Maris, Li Changwei, Musani Solomon K, Marten Jonathan, Vojinovic Dina, Sim Xueling, Cheng Ching-Yu, Lu Yingchang, Franceschini Nora, Guo Xiuqing, Ntalla Ioanna, Schwander Karen, Kraja Aldi T, Brown Michael R, Bentley Amy R, de Las Fuentes Lisa, Winkler Thomas W, Feitosa Mary F, Kilpeläinen Tuomas O, Richard Melissa A, Sofer Tamar, Matoba Nana, Zhou Yanhua, Zhao Wei, Warren Helen R, Tayo Bamidele O, Tajuddin Salman M, Smith Albert Vernon, Rankinen Tuomo, Manning Alisa K, Liu Yongmei, Dorajoo Rajkumar, Bartz Traci M, Aschard Hugues, Aslibekyan Stella, Noordam Raymond, Sung Yun J, Lehne Benjamin, Howard Barbara V, Hofman Albert, Hirata Makoto, Heng Chew-Kiat, Heikkinen Sami, He Jiang, Harris Tamara B, Hagenaars Saskia P, Gupta Preeti, Gu Dongfeng, Gu C Charles, Graff Misa, Gigante Bruna, GIANT Consortium, Gao He, Friedlander Yechiel, Hunt Steven, Irvin Marguerite R, Jia Yucheng, Launer Lenore J, Langenberg Claudia, Langefeld Carl D, Kuusisto Johanna, Kubo Michiaki, Krieger Jose E, Kooperberg Charles, Komulainen Pirjo, Koistinen Heikki A, Koh Woon-Puay, Khor Chiea Chuen, Kerrison Nicola D, Kaufman Joel, Katsuya Tomohiro, Justice Anne E, Joehanes Roby, Franco Oscar H, Forouhi Nita G, Fisher Virginia A, Caizheng Yu, Cade Brian, Cabrera Claudia P, Broeckel Ulrich, Brody Jennifer A, Braund Peter S, Bottinger Erwin P, Boerwinkle Eric, Bielak Lawrence F, Barr R Graham, Aung Tin, Arking Dan, Amin Najaf, Alfred Tamuno, Afaq Saima, Zhao Jing Hua, Campbell Archie, Canouil Mickaël, Chakravarti Aravinda, Faul Jessica D, Evangelou Evangelos, Ehret Georg, Eaton Charles B, Duan Qing, Dörr Marcus, Debette Stephanie, de Silva H Janaka, de Mutsert Renée, Connell John M, Collins Francis S, COGENT-Kidney Consortium, Cocca Massimiliano, Christensen Kaare, Chauhan Ganesh, CHARGE Neurology Working Group, Zhang Weihua

Citation

Bowden D, Snieder H, Smith J, Sitlani C, Sever P, Seshadri S, Scott W, Schreiner P, Schmidt C, Sandow K, Salako B, Sabanayagam C, Rudan I, Rose L, Robinson J, Robino A, Ridker P, Starr J, Strauch K, Tang H, Boehnke M, Becker D, Zonderman A, Yuan J, Yao J, Wojczynski M, Wilson G, Williams C, Wei W, Wang Y, Wang L, Waldenberger M, Uitterlinden A, Tham Y, Teo Y, Taylor K, Rice T, Renström F, Raitakari O, Metspalu A, Meitinger T, Mahajan A, Mägi R, Louie T, Long J, Lohman K, Loh M, Liu Y, Liu K, Liu J, Liu J, Liu C, Lin S, Lim S, Lifelines Cohort Study, Milani L, Momozawa Y, Morris A, Polasek O, Peyser P, Peters A, Pedersen N, Pankow J, Palmer N, Palmas W, Padmanabhan S, Ogunniyi A, North K, Norris J, Nasri U, Nalls M, Murray A, Munson P, Mosley T, Li Y, Chasman D, Hayward C, Fox E, Kelly T, Mook-Kanamori D, Arnett D, Sims M, van Dam R, Psaty B, O'Connell J, Levy D, Kritchevsky S, Kardia S, Gudnason V, Evans M, Cooper R, Bouchard C, Fornage M, Rotimi C, Province M, Rao D, Cupples L, Morrison A, Munroe P, Rice K, Elliott P, Caulfield M, Gauderman W, Bierut L, Zhu X, Rotter J, Reiner A, Loos R, Wong T, Tai E, van Duijn C, Laurie C, Kamatani Y, Zheng W, Kooner J, Kato N, Jonas J, Hung Y, Horta B, Gieger C, Gasparini P, Froguel P, Freedman B, Franks P, Forrester T, Farrall M, Esko T, Deary I, de Faire U, Chen Y, Laakso M, Lehtimäki T, Liang K, Wu T, Wickremasinghe A, Weir D, Watkins H, Wareham N, Wagenknecht L, van der Harst P, Shu X, Scott J, Samani N, Rettig R, Redline S, Pereira A, Oldehinkel A, Newman A, Magnusson P, Chambers J, Lewis C, Yanek L, Leander K, Kühnel B, Kasturiratne A, Kähönen M, Jackson A, Hsu F, Horimoto A, Hartwig F, Harris S, Goel A, Giulianini F, Gao C, Gandin I, Divers J, Chen X, Chai J, Lee W, Lin K, 'an Luan J, Wen W, Weiss S, Ware E, Wang Y, Wang H, Varga T, van der Most P, Takeuchi F, Stančáková A, Sheu W, Scott R, Schupf N, Rauramaa R, Nelson C, He M, McKenzie C, Boissel M, Amini M, Alver M, Li C, Musani S, Marten J, Vojinovic D, Sim X, Cheng C, Lu Y, Franceschini N, Guo X, Ntalla I, Schwander K, Kraja A, Brown M, Bentley A, de Las Fuentes L, Winkler T, Feitosa M, Kilpeläinen T, Richard M, Sofer T, Matoba N, Zhou Y, Zhao W, Warren H, Tayo B, Tajuddin S, Smith A, Rankinen T, Manning A, Liu Y, Dorajoo R, Bartz T, Aschard H, Aslibekyan S, Noordam R, Sung Y, Lehne B, Howard B, Hofman A, Hirata M, Heng C, Heikkinen S, He J, Harris T, Hagenaars S, Gupta P, Gu D, Gu C, Graff M, Gigante B, GIANT Consortium, Gao H, Friedlander Y, Hunt S, Irvin M, Jia Y, Launer L, Langenberg C, Langefeld C, Kuusisto J, Kubo M, Krieger J, Kooperberg C, Komulainen P, Koistinen H, Koh W, Khor C, Kerrison N, Kaufman J, Katsuya T, Justice A, Joehanes R, Franco O, Forouhi N, Fisher V, Caizheng Y, Cade B, Cabrera C, Broeckel U, Brody J, Braund P, Bottinger E, Boerwinkle E, Bielak L, Barr R, Aung T, Arking D, Amin N, Alfred T, Afaq S, Zhao J, Campbell A, Canouil M, Chakravarti A, Faul J, Evangelou E, Ehret G, Eaton C, Duan Q, Dörr M, Debette S, de Silva H, de Mutsert R, Connell J, Collins F, COGENT-Kidney Consortium, Cocca M, Christensen K, Chauhan G, CHARGE Neurology Working Group, Zhang W. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure. Am J Hum Genet 2018; 102:375-400.

Type

Journal Paper/Review (English)

Journal

Am J Hum Genet 2018; 102

Publication Date

Feb 15, 2018

Issn Electronic

1537-6605

Pages

375-400

Brief description/objective

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 ∼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 × 10) 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 × 10). 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).