Abstract
Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
| Original language | English |
|---|---|
| Pages (from-to) | 2615-2633 |
| Number of pages | 19 |
| Journal | Human molecular genetics |
| Volume | 28 |
| Issue number | 15 |
| DOIs | |
| State | Published - Aug 1 2019 |
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In: Human molecular genetics, Vol. 28, No. 15, 01.08.2019, p. 2615-2633.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
AU - Sung, Yun Ju
AU - De Las Fuentes, Lisa
AU - Winkler, Thomas W.
AU - Chasman, Daniel I.
AU - Bentley, Amy R.
AU - Kraja, Aldi T.
AU - Ntalla, Ioanna
AU - Warren, Helen R.
AU - Guo, Xiuqing
AU - Schwander, Karen
AU - Manning, Alisa K.
AU - Brown, Michael R.
AU - Aschard, Hugues
AU - Feitosa, Mary F.
AU - Franceschini, Nora
AU - Lu, Yingchang
AU - Cheng, Ching Yu
AU - Sim, Xueling
AU - Vojinovic, Dina
AU - Marten, Jonathan
AU - Musani, Solomon K.
AU - Kilpeläinen, Tuomas O.
AU - Richard, Melissa A.
AU - Aslibekyan, Stella
AU - Bartz, Traci M.
AU - Dorajoo, Rajkumar
AU - Li, Changwei
AU - Liu, Yongmei
AU - Rankinen, Tuomo
AU - Smith, Albert Vernon
AU - Tajuddin, Salman M.
AU - Tayo, Bamidele O.
AU - Zhao, Wei
AU - Zhou, Yanhua
AU - Matoba, Nana
AU - Sofer, Tamar
AU - Alver, Maris
AU - Amini, Marzyeh
AU - Boissel, Mathilde
AU - Chai, Jin Fang
AU - Chen, Xu
AU - Divers, Jasmin
AU - Gandin, Ilaria
AU - Gao, Chuan
AU - Giulianini, Franco
AU - Goel, Anuj
AU - Harris, Sarah E.
AU - Hartwig, Fernando P.
AU - He, Meian
AU - Horimoto, Andrea R.V.R.
AU - Hsu, Fang Chi
AU - Jackson, Anne U.
AU - Kammerer, Candace M.
AU - Kasturiratne, Anuradhani
AU - Komulainen, Pirjo
AU - Kühnel, Brigitte
AU - Leander, Karin
AU - Lee, Wen Jane
AU - Lin, Keng Hung
AU - Luan, Jian'an
AU - Lyytikäinen, Leo Pekka
AU - McKenzie, Colin A.
AU - Nelson, Christopher P.
AU - Noordam, Raymond
AU - Scott, Robert A.
AU - Sheu, Wayne H.H.
AU - Stančáková, Alena
AU - Takeuchi, Fumihiko
AU - Van Der Most, Peter J.
AU - Varga, Tibor V.
AU - Waken, Robert J.
AU - Wang, Heming
AU - Wang, Yajuan
AU - Ware, Erin B.
AU - Weiss, Stefan
AU - Wen, Wanqing
AU - Yanek, Lisa R.
AU - Zhang, Weihua
AU - Zhao, Jing Hua
AU - Afaq, Saima
AU - Alfred, Tamuno
AU - Amin, Najaf
AU - Arking, Dan E.
AU - Aung, Tin
AU - Barr, R. Graham
AU - Bielak, Lawrence F.
AU - Boerwinkle, Eric
AU - Bottinger, Erwin P.
AU - Braund, Peter S.
AU - Brody, Jennifer A.
AU - Broeckel, Ulrich
AU - Cade, Brian
AU - Campbell, Archie
AU - Canouil, Mickaël
AU - Chakravarti, Aravinda
AU - Cocca, Massimiliano
AU - Collins, Francis S.
AU - Connell, John M.
AU - De Mutsert, Renée
AU - De Silva, H. Janaka
AU - Dörr, Marcus
AU - Duan, Qing
AU - Eaton, Charles B.
AU - Ehret, Georg
AU - Evangelou, Evangelos
AU - Faul, Jessica D.
AU - Forouhi, Nita G.
AU - Franco, Oscar H.
AU - Friedlander, Yechiel
AU - Gao, He
AU - Gigante, Bruna
AU - Gu, C. Charles
AU - Gupta, Preeti
AU - Hagenaars, Saskia P.
AU - Harris, Tamara B.
AU - He, Jiang
AU - Heikkinen, Sami
AU - Heng, Chew Kiat
AU - Hofman, Albert
AU - Howard, Barbara V.
AU - Hunt, Steven C.
AU - Irvin, Marguerite R.
AU - Jia, Yucheng
AU - Katsuya, Tomohiro
AU - Kaufman, Joel
AU - Kerrison, Nicola D.
AU - Khor, Chiea Chuen
AU - Koh, Woon Puay
AU - Koistinen, Heikki A.
AU - Kooperberg, Charles B.
AU - Krieger, Jose E.
AU - Kubo, Michiaki
AU - Kutalik, Zoltan
AU - Kuusisto, Johanna
AU - Lakka, Timo A.
AU - Langefeld, Carl D.
AU - Langenberg, Claudia
AU - Launer, Lenore J.
AU - Lee, Joseph H.
AU - Lehne, Benjamin
AU - Levy, Daniel
AU - Lewis, Cora E.
AU - Li, Yize
AU - Lim, Sing Hui
AU - Liu, Ching Ti
AU - Liu, Jianjun
AU - Liu, Jingmin
AU - Liu, Yeheng
AU - Loh, Marie
AU - Lohman, Kurt K.
AU - Louie, Tin
AU - Mägi, Reedik
AU - Matsuda, Koichi
AU - Meitinger, Thomas
AU - Metspalu, Andres
AU - Milani, Lili
AU - Momozawa, Yukihide
AU - Thomas, Thomas H.
AU - Nalls, Mike A.
AU - Nasri, Ubaydah
AU - O'Connell, Jeff R.
AU - Ogunniyi, Adesola
AU - Palmas, Walter R.
AU - Palmer, Nicholette D.
AU - Pankow, James S.
AU - Pedersen, Nancy L.
AU - Peters, Annette
AU - Peyser, Patricia A.
AU - Polasek, Ozren
AU - Porteous, David
AU - Raitakari, Olli T.
AU - Renström, Frida
AU - Rice, Treva K.
AU - Ridker, Paul M.
AU - Robino, Antonietta
AU - Robinson, Jennifer G.
AU - Rose, Lynda M.
AU - Rudan, Igor
AU - Sabanayagam, Charumathi
AU - Salako, Babatunde L.
AU - Sandow, Kevin
AU - Schmidt, Carsten O.
AU - Schreiner, Pamela J.
AU - Scott, William R.
AU - Sever, Peter
AU - Sims, Mario
AU - Sitlani, Colleen M.
AU - Smith, Blair H.
AU - Smith, Jennifer A.
AU - Snieder, Harold
AU - Starr, John M.
AU - Strauch, Konstantin
AU - Tang, Hua
AU - Taylor, Kent D.
AU - Teo, Yik Ying
AU - Tham, Yih Chung
AU - Uitterlinden, André G.
AU - Waldenberger, Melanie
AU - Wang, Lihua
AU - Wang, Ya Xing
AU - Wei, Wen Bin
AU - Wilson, Gregory
AU - Wojczynski, Mary K.
AU - Xiang, Yong Bing
AU - Yao, Jie
AU - Yuan, Jian Min
AU - Zonderman, Alan B.
AU - Becker, Diane M.
AU - Boehnke, Michael
AU - Bowden, Donald W.
AU - Chambers, John C.
AU - Chen, Yii Der Ida
AU - Weir, David R.
AU - De Faire, Ulf
AU - Deary, Ian J.
AU - Esko, Tõnu
AU - Farrall, Martin
AU - Forrester, Terrence
AU - Freedman, Barry I.
AU - Froguel, Philippe
AU - Gasparini, Paolo
AU - Gieger, Christian
AU - Horta, Bernardo Lessa
AU - Hung, Yi Jen
AU - Jonas, Jost Bruno
AU - Kato, Norihiro
AU - Kooner, Jaspal S.
AU - Laakso, Markku
AU - Lehtimäki, Terho
AU - Liang, Kae Woei
AU - Magnusson, Patrik K.E.
AU - Oldehinkel, Albertine J.
AU - Pereira, Alexandre C.
AU - Perls, Thomas
AU - Rauramaa, Rainer
AU - Redline, Susan
AU - Rettig, Rainer
AU - Samani, Nilesh J.
AU - Scott, James
AU - Shu, Xiao Ou
AU - Van Der Harst, Pim
AU - Wagenknecht, Lynne E.
AU - Wareham, Nicholas J.
AU - Watkins, Hugh
AU - Wickremasinghe, Ananda R.
AU - Wu, Tangchun
AU - Kamatani, Yoichiro
AU - Laurie, Cathy C.
AU - Bouchard, Claude
AU - Cooper, Richard S.
AU - Evans, Michele K.
AU - Gudnason, Vilmundur
AU - Hixson, James
AU - Kardia, Sharon L.R.
AU - Kritchevsky, Stephen B.
AU - Psaty, Bruce M.
AU - Van Dam, Rob M.
AU - Arnett, Donna K.
AU - Mook-Kanamori, Dennis O.
AU - Fornage, Myriam
AU - Fox, Ervin R.
AU - Hayward, Caroline
AU - Van Duijn, Cornelia M.
AU - Tai, E. Shyong
AU - Wong, Tien Yin
AU - Loos, Ruth J.F.
AU - Reiner, Alex P.
AU - Rotimi, Charles N.
AU - Bierut, Laura J.
AU - Zhu, Xiaofeng
AU - Cupples, L. Adrienne
AU - Province, Michael A.
AU - Rotter, Jerome I.
AU - Franks, Paul W.
AU - Rice, Kenneth
AU - Elliott, Paul
AU - Caulfield, Mark J.
AU - Gauderman, W. James
AU - Munroe, Patricia B.
AU - Rao, Dabeeru C.
AU - Morrison, Alanna C.
N1 - Publisher Copyright: © 2019 The Author(s). Published by Oxford University Press. All rights reserved.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
AB - Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
UR - http://www.scopus.com/inward/record.url?scp=85078574203&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddz070
DO - 10.1093/hmg/ddz070
M3 - Article
C2 - 31127295
AN - SCOPUS:85078574203
SN - 0964-6906
VL - 28
SP - 2615
EP - 2633
JO - Human molecular genetics
JF - Human molecular genetics
IS - 15
ER -