Dataset Information

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure.

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.

SUBMITTER: Sung YJ

PROVIDER: S-EPMC6644157 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure.

Sung Yun Ju YJ de las Fuentes Lisa L Winkler Thomas W TW Chasman Daniel I DI Bentley Amy R AR Kraja Aldi T AT Ntalla Ioanna I Warren Helen R HR Guo Xiuqing X Schwander Karen K Manning Alisa K AK Brown Michael R MR Aschard Hugues H Feitosa Mary F MF Franceschini Nora N Lu Yingchang Y Cheng Ching-Yu CY Sim Xueling X Vojinovic Dina D Marten Jonathan J Musani Solomon K SK Kilpeläinen Tuomas O TO Richard Melissa A MA Aslibekyan Stella S Bartz Traci M TM Dorajoo Rajkumar R Li Changwei C Liu Yongmei Y Rankinen Tuomo T Smith Albert Vernon AV Tajuddin Salman M SM Tayo Bamidele O BO Zhao Wei W Zhou Yanhua Y Matoba Nana N Sofer Tamar T Alver Maris M Amini Marzyeh M Boissel Mathilde M Chai Jin Fang JF Chen Xu X Divers Jasmin J Gandin Ilaria I Gao Chuan C Giulianini Franco F Goel Anuj A Harris Sarah E SE Hartwig Fernando P FP He Meian M Horimoto Andrea R V R ARVR Hsu Fang-Chi FC Jackson Anne U AU Kammerer Candace M CM Kasturiratne Anuradhani A Komulainen Pirjo P Kühnel Brigitte B Leander Karin K Lee Wen-Jane WJ Lin Keng-Hung KH Luan Jian'an J Lyytikäinen Leo-Pekka LP McKenzie Colin A CA Nelson Christopher P CP Noordam Raymond R Scott Robert A RA Sheu Wayne H H WHH Stančáková Alena A Takeuchi Fumihiko F van der Most Peter J PJ Varga Tibor V TV Waken Robert J RJ Wang Heming H Wang Yajuan Y Ware Erin B EB Weiss Stefan S Wen Wanqing W Yanek Lisa R LR Zhang Weihua W Zhao Jing Hua JH Afaq Saima S Alfred Tamuno T Amin Najaf N Arking Dan E DE Aung Tin T Barr R Graham RG Bielak Lawrence F LF Boerwinkle Eric E Bottinger Erwin P EP Braund Peter S PS Brody Jennifer A JA Broeckel Ulrich U Cade Brian B Campbell Archie A Canouil Mickaël M Chakravarti Aravinda A Cocca Massimiliano M Collins Francis S FS Connell John M JM de Mutsert Renée R de Silva H Janaka HJ Dörr Marcus M Duan Qing Q Eaton Charles B CB Ehret Georg G Evangelou Evangelos E Faul Jessica D JD Forouhi Nita G NG Franco Oscar H OH Friedlander Yechiel Y Gao He H Gigante Bruna B Gu C Charles CC Gupta Preeti P Hagenaars Saskia P SP Harris Tamara B TB He Jiang J Heikkinen Sami S Heng Chew-Kiat CK Hofman Albert A Howard Barbara V BV Hunt Steven C SC Irvin Marguerite R MR Jia Yucheng Y Katsuya Tomohiro T Kaufman Joel J Kerrison Nicola D ND Khor Chiea Chuen CC Koh Woon-Puay WP Koistinen Heikki A HA Kooperberg Charles B CB Krieger Jose E JE Kubo Michiaki M Kutalik Zoltan Z Kuusisto Johanna J Lakka Timo A TA Langefeld Carl D CD Langenberg Claudia C Launer Lenore J LJ Lee Joseph H JH Lehne Benjamin B Levy Daniel D Lewis Cora E CE Li Yize Y Lim Sing Hui SH Liu Ching-Ti CT Liu Jianjun J Liu Jingmin J Liu Yeheng Y Loh Marie M Lohman Kurt K KK Louie Tin T Mägi Reedik R Matsuda Koichi K Meitinger Thomas T Metspalu Andres A Milani Lili L Momozawa Yukihide Y Mosley Thomas H TH Nalls Mike A MA Nasri Ubaydah U O'Connell Jeff R JR Ogunniyi Adesola A Palmas Walter R WR Palmer Nicholette D ND Pankow James S JS Pedersen Nancy L NL Peters Annette A Peyser Patricia A PA Polasek Ozren O Porteous David D Raitakari Olli T OT Renström Frida F Rice Treva K TK Ridker Paul M PM Robino Antonietta A Robinson Jennifer G JG Rose Lynda M LM Rudan Igor I Sabanayagam Charumathi C Salako Babatunde L BL Sandow Kevin K Schmidt Carsten O CO Schreiner Pamela J PJ Scott William R WR Sever Peter P Sims Mario M Sitlani Colleen M CM Smith Blair H BH Smith Jennifer A JA Snieder Harold H Starr John M JM Strauch Konstantin K Tang Hua H Taylor Kent D KD Teo Yik Ying YY Tham Yih Chung YC Uitterlinden André G AG Waldenberger Melanie M Wang Lihua L Wang Ya Xing YX Wei Wen Bin WB Wilson Gregory G Wojczynski Mary K MK Xiang Yong-Bing YB Yao Jie J Yuan Jian-Min JM Zonderman Alan B AB Becker Diane M DM Boehnke Michael M Bowden Donald W DW Chambers John C JC Chen Yii-Der Ida YI Weir David R DR de Faire Ulf U Deary Ian J IJ Esko Tõnu T Farrall Martin M Forrester Terrence T Freedman Barry I BI Froguel Philippe P Gasparini Paolo P Gieger Christian C Horta Bernardo Lessa BL Hung Yi-Jen YJ Jonas Jost Bruno JB Kato Norihiro N Kooner Jaspal S JS Laakso Markku M Lehtimäki Terho T Liang Kae-Woei KW Magnusson Patrik K E PKE Oldehinkel Albertine J AJ Pereira Alexandre C AC Perls Thomas T Rauramaa Rainer R Redline Susan S Rettig Rainer R Samani Nilesh J NJ Scott James J Shu Xiao-Ou XO van der Harst Pim P Wagenknecht Lynne E LE Wareham Nicholas J NJ Watkins Hugh H Wickremasinghe Ananda R AR Wu Tangchun T Kamatani Yoichiro Y Laurie Cathy C CC Bouchard Claude C Cooper Richard S RS Evans Michele K MK Gudnason Vilmundur V Hixson James J Kardia Sharon L R SLR Kritchevsky Stephen B SB Psaty Bruce M BM van Dam Rob M RM Arnett Donna K DK Mook-Kanamori Dennis O DO Fornage Myriam M Fox Ervin R ER Hayward Caroline C van Duijn Cornelia M CM Tai E Shyong ES Wong Tien Yin TY Loos Ruth J F RJF Reiner Alex P AP Rotimi Charles N CN Bierut Laura J LJ Zhu Xiaofeng X Cupples L Adrienne LA Province Michael A MA Rotter Jerome I JI Franks Paul W PW Rice Kenneth K Elliott Paul P Caulfield Mark J MJ Gauderman W James WJ Munroe Patricia B PB Rao Dabeeru C DC Morrison Alanna C AC

Human molecular genetics 20190801 15

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 ...[more]

PMID: 31127295

Similar Datasets

Project description:BackgroundPulse pressure (PP) and mean arterial pressure (MAP) are well-established markers of cardiovascular risk. In this study, we aimed to assess the temporal trend and associated factors of PP and MAP in Chinese children and adolescents.MethodsFrom the China Health and Nutrition Survey 1991-2015, a total of 11,123 children and adolescents aged 7-17 years were included. Stratified analyses and generalized estimating equation (GEE) were conducted to compare the trends of PP and MAP by age and sex over two decades, along with the calculation of average relative increase (ARI). Moreover, multivariable linear regression was used to estimate the associated factors of PP and MAP.ResultsDuring 1991-2015, upward trends were observed in both PP and MAP levels, with ARI of 0.30 and 0.34%, respectively. PP was higher in boys [PP1991 33.9 mmHg (95%CI, 33.40-34.33) to PP2015 35.4 mmHg (34.74-36.15)] than in girls [PP1991 33.3 mmHg (32.83-33.72) to PP2015 34.3 mmHg (33.59-34.99)]. PP was also higher in participants aged 13-17 years [PP1991 36.1 mmHg (35.63-36.62) to PP2015 38.3 mmHg (37.35-39.21)] than in those aged 7-12 years [PP1991 31.5 mmHg (31.09-31.88) to PP2015 33.7 mmHg (33.16-34.30)]. Similar results were found in MAP. Participants with high economic status, general obesity and central obesity, were more likely to have wider PP (β higheconomicstatus = 0.60, 95% CI, 0.19-1.02; β generalobesity = 1.38, 0.87-1.89; β centralobesity = 1.34, 0.70-1.97; all P-values < 0.001) and higher MAP (β higheconomicstatus = 0.82, 0.38-1.26; β generalobesity = 2.88, 2.33-3.42; β centralobesity = 3.14, 2.47-3.80; all P-values < 0.001). Body mass index (BMI) and waist circumference (WC) were positively correlated with PP (β BMI = 0.18, 0.13-0.24; β WC = 0.10, 0.08-0.12; both P-values < 0.001) and MAP (β BMI = 0.43, 0.37-0.49; β WC = 0.20, 0.18-0.22; both P-values < 0.001). In addition, rural setting and glucose level were positively associated with PP (both P < 0.05), while north region residency, uric acid, and total cholesterol were found to be positively associated with MAP (all P < 0.05).ConclusionPP and MAP levels have been increasing dramatically in Chinese children and adolescents over the last two decades. Age, sex, economic status, geographic factors, anthropometric and cardiometabolic factor were positively associated with PP and MAP in pediatric population.

Dataset Information

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure.

Publications

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets