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Hum Mol Genet. 2019 Apr 10. pii: ddz070. doi: 10.1093/hmg/ddz070. [Epub ahead of print]

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

Sung YJ1, de Las Fuentes L1,2, Winkler TW3, Chasman DI4, Bentley AR5, Kraja AT6, Ntalla I7, Warren HR7,8, Guo X9, Schwander K1, Manning AK10,11, Brown MR12, Aschard H13,14, Feitosa MF6, Franceschini N15, Lu Y16, Cheng CY17,18,19, Sim X20, Vojinovic D21, Marten J22, Musani SK23, Kilpeläinen TO24,25, Richard MA26, Aslibekyan S27, Bartz TM28, Dorajoo R29, Li C30, Liu Y31, Rankinen T32, Smith AV33,34, Tajuddin SM35, Tayo BO36, Zhao W37, Zhou Y38, Matoba N39, Sofer T40,41, Alver M42, Amini M43, Boissel M44, Chai JF20, Chen X45, Divers J46, Gandin I47, Gao C48, Giulianini F4, Goel A49,50, Harris SE51,52, Hartwig FP53,54, He M55, Horimoto ARVR56, Hsu FC46, Jackson AU57, Kammerer CM58, Kasturiratne A59, Komulainen P60, Kühnel B61,62, Leander K63, Lee WJ64, Lin KH65, Luan J66, Lyytikäinen LP67,68, McKenzie CA69, Nelson CP70,71, Noordam R72, Scott RA66, Sheu WHH73,74,75,76, Stančáková A77, Takeuchi F78, van der Most PJ43, Varga TV79, Waken RJ1, Wang H40,41, Wang Y80, Ware EB37,81, Weiss S82,83, Wen W84, Yanek LR85, Zhang W86,87, Zhao JH66, Afaq S86, Alfred T16, Amin N21, Arking DE88, Aung T17,18,19, Barr RG89, Bielak LF37, Boerwinkle E12,90, Bottinger EP16, Braund PS70,71, Brody JA91, Broeckel U92, Cade B41, Campbell A93, Canouil M44, Chakravarti A88, Cocca M47, Collins FS94, Connell JM95, de Mutsert R96, de Silva HJ97, Dörr M83,98, Duan Q99, Eaton CB100, Ehret G88,101, Evangelou E86,102, Faul JD81, Forouhi NG66, Franco OH21, Friedlander Y103, Gao H86, Gigante B63, Gu CC1, Gupta P17, Hagenaars SP51,104, Harris TB105, He J106,107, Heikkinen S77,108, Heng CK109,110, Hofman A21, Howard BV111,112, Hunt SC113,114, Irvin MR115, Jia Y9, Katsuya T116,117, Kaufman J118, Kerrison ND66, Khor CC29,119, Koh WP20,120, Koistinen HA121,122,123, Kooperberg CB124, Krieger JE56, Kubo M125, Kutalik Z126,127, Kuusisto J77, Lakka TA60,108,128, Langefeld CD46, Langenberg C66, Launer LJ105, Lee JH129, Lehne B86, Levy D130,131, Lewis CE132, Li Y1; Lifelines Cohort Study, Lim SH17, Liu CT38, Liu J20,29, Liu J133, Liu Y9, Loh M86,134, Lohman KK46, Louie T135, Mägi R42, Matsuda K136, Meitinger T137,138, Metspalu A42, Milani L2, Momozawa Y139, Mosley TH Jr140, Nalls MA141, Nasri U9, O'Connell JR142,143, Ogunniyi A144, Palmas WR145, Palmer ND146, Pankow JS147, Pedersen NL45, Peters A61,148, Peyser PA37, Polasek O149,150,151, Porteous D93, Raitakari OT152,153, Renström F79,154, Rice TK1, Ridker PM4, Robino A155, Robinson JG156, Rose LM4, Rudan I157, Sabanayagam C17,18, Salako BL144, Sandow K9, Schmidt CO83,158, Schreiner PJ147, Scott WR86,159, Sever P160, Sims M23, Sitlani CM91, Smith BH161, Smith JA37,81, Snieder H43, Starr JM51,162, Strauch K163,164, Tang H165, Taylor KD9, Teo YY20,29,166,167,168, Tham YC17, Uitterlinden AG169, Waldenberger M60,61,65, Wang L6, Wang YX170, Wei WB171, Wilson G172, Wojczynski MK6, Xiang YB173, Yao J9, Yuan JM174,175, Zonderman AB176, Becker DM85, Boehnke M56, Bowden DW146, Chambers JC86,87, Chen YI9, Weir DR81, de Faire U62, Deary IJ51,104, Esko T42,177, Farrall M49,50, Forrester T68, Freedman BI178, Froguel P44,179, Gasparini P47,114, Gieger C60,61,180, Horta BL53, Hung YJ181, Jonas JB171,182, Kato N78, Kooner JS87,159, Laakso M77, Lehtimäki T66,67, Liang KW74,183,184, Magnusson PKE45, Oldehinkel AJ185, Pereira AC55,186, Perls T187, Rauramaa R59, Redline S41, Rettig R83,188, Samani NJ70,71, Scott J159, Shu XO84, van der Harst P189, Wagenknecht LE190, Wareham NJ65, Watkins H49,50, Wickremasinghe AR58, Wu T69, Kamatani Y39, Laurie CC135, Bouchard C32, Cooper RS36, Evans MK35, Gudnason V33,34, Hixson J12, Kardia SLR37, Kritchevsky SB191, Psaty BM192,193, van Dam RM20,194, Arnett DK195, Mook-Kanamori DO96,196, Fornage M26, Fox ER197, Hayward C22, van Duijn CM21, Tai ES20,120,194, Wong TY17,18,19, Loos RJF16,198, Reiner AP124, Rotimi CN5, Bierut LJ199, Zhu X80, Cupples LA38, Province MA6, Rotter JI9, Franks PW79,200,201, Rice K135, Elliott P86, Caulfield MJ7,8, Gauderman WJ202, Munroe PB7,8, Rao DC1, Morrison AC12.

Author information

1
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
2
Cardiovascular Division, Department of Medicine, Washington University, St. Louis, MO, USA.
3
Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
4
Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
5
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
6
Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
7
Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
8
NIHR Barts Cardiovascular Biomedical Research Centre, Queen Mary University of London, London, London, UK.
9
Division of Genomic Outcomes, Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
10
Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA.
11
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
12
Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
13
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
14
Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur, Paris, France.
15
Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA.
16
Icahn School of Medicine at Mount Sinai, The Charles Bronfman Institute for Personalized Medicine, New York, NY, USA.
17
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
18
Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore.
19
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
20
Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, Singapore.
21
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
22
Medical Research Council Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
23
Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
24
Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
25
Department of Environmental Medicine and Public Health, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
26
Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
27
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
28
Cardiovascular Health Research Unit, Biostatistics and Medicine, University of Washington, Seattle, WA, USA.
29
Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore.
30
Epidemiology and Biostatistics, University of Georgia at Athens College of Public Health, Athens, GA, USA.
31
Public Health Sciences, Epidemiology and Prevention, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
32
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
33
Icelandic Heart Association, Kopavogur, Iceland.
34
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
35
Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
36
Department of Public Health Sciences, Loyola University Chicago, Maywood, IL, USA.
37
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
38
Biostatistics, Boston University School of Public Health, Boston, MA, USA.
39
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
40
Department of Medicine, Harvard Medical School, Boston, MA, USA.
41
Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.
42
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
43
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen RB, The Netherlands.
44
CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, France.
45
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Stockholm, Sweden.
46
Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
47
Department of Medical Sciences, University of Trieste, Trieste, Italy.
48
Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, NC, USA.
49
Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK.
50
Wellcome Centre for Human Genetics, University of Oxford, Oxford, Oxfordshire, UK.
51
Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK.
52
Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
53
Postgraduate Programme in Epidemiology, Federal University of Pelotas, Pelotas, RS, Brazil.
54
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
55
Lab Genetics and Molecular Cardiology, Cardiology, Heart Institute, University of Sao Paulo, Sao Paulo, CA, USA.
56
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
57
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
58
Department of Public Health, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
59
Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
60
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
61
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
62
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
63
Medical Research, Taichung Veterans General Hospital, Department of Social Work, Tunghai University, Taichung, Taiwan.
64
Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan.
65
MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
66
Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
67
Department of Clinical Chemistry, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
68
Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Jamaica.
69
School of Public Health, Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, Tongi Medical College, Huazhong University of Science and Technology, Wuhan, China.
70
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
71
NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
72
Internal Medicine, Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
73
Endocrinology and Metabolism, Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
74
School of Medicine, National Yang-ming University, Taipei, Taiwan.
75
School of Medicine, National Defense Medical Center, Taipei, Taiwan.
76
Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan.
77
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
78
Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
79
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden.
80
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
81
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
82
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Ernst Moritz Arndt University Greifswald, Greifswald, Germany.
83
DZHK (German Centre for Cardiovascular Health), Partner Site Greifswald, Greifswald, Germany.
84
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
85
General Internal Medicine, GeneSTAR Research Program, Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
86
MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
87
Department of Cardiology, Ealing Hospital, Middlesex, UK.
88
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
89
Departments of Medicine and Epidemiology, Columbia University Medical Center, New York, NY, USA.
90
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
91
Cardiovascular Health Research Unit, Medicine, University of Washington, Seattle, WA, USA.
92
Section of Genomic Pediatrics, Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
93
Centre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK.
94
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
95
Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, UK.
96
Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
97
Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
98
Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
99
Department of Genetics, University of North Carolina, Chapel Hill, USA.
100
Department of Family Medicine and Epidemiology, Alpert Medical School of Brown University, Providence, RI, USA.
101
Cardiology, Department of Specialties of Medicine, Geneva University Hospital, Geneva, Switzerland.
102
Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
103
Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
104
Psychology, The University of Edinburgh, Edinburgh, UK.
105
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
106
Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
107
Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
108
Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, Finland.
109
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
110
Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore.
111
MedStar Health Research Institute, Hyattsville, MD, USA.
112
Center for Clinical and Translational Sciences and Department of Medicine, Georgetown-Howard Universities, Washington, DC, USA.
113
Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
114
Department of Genetic Medicine, Weill Cornell Medicine, Doha, Qatar.
115
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
116
Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Japan.
117
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Japan.
118
Epidemiology, Occupational and Environmental Medicine Program, University of Washington, Seattle, WA, USA.
119
Department of Biochemistry, National University of Singapore, Singapore, Singapore.
120
Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore.
121
Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.
122
Department of Medicine and Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
123
Minerva Foundation Institute for Medical Research, Biomedicum 2U, Helsinki Finland.
124
Fred Hutchinson Cancer Research Center, University of Washington School of Public Health, Seattle, WA, USA.
125
RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
126
Institute of Social Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
127
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
128
Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
129
Sergievsky Center, College of Physicians and Surgeons, Columbia University Mailman School of Public Health, New York, NY, USA.
130
NHLBI Framingham Heart Study, Framingham, MA, USA.
131
The Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
132
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
133
WHI CCC, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
134
Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore.
135
Department of Biostatistics, University of Washington, Seattle, WA, USA.
136
Laboratory for Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Minato-ku, Japan.
137
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
138
Institute of Human Genetics, Technische Universität München, Munich, Germany.
139
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
140
Geriatrics, Medicine, University of Mississippi, Jackson, MS, USA.
141
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
142
Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.
143
Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
144
Department of Medicine, University of Ibadan, Ibadan, Nigeria.
145
Internal Medicine, Columbia University, New York, NY, USA.
146
Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
147
Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.
148
DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Neuherberg, Germany.
149
Department of Public Health, Department of Medicine, University of Split, Split, Croatia.
150
Psychiatric Hospital 'Sveti Ivan', Zagreb, Croatia.
151
Gen-info Ltd, Zagreb, Croatia.
152
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
153
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
154
Department of Biobank Research, Umeå University, Umeå, Västerbotten, Sweden.
155
Institute for Maternal and Child Health-IRCCS 'Burlo Garofolo', Trieste, Italy.
156
Department of Epidemiology and Medicine, University of Iowa, Iowa City, IA, USA.
157
Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
158
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
159
National Heart and Lung Institute, Imperial College London, London, UK.
160
International Centre for Circulatory Health, Imperial College London, London, UK.
161
Division of Population Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
162
Alzheimer Scotland Dementia Research Centre, The University of Edinburgh, Edinburgh, UK.
163
Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
164
Genetic Epidemiology, IBE, Faculty of Medicine, LMU, Munich, Germany.
165
Department of Genetics, Stanford University, Stanford, CA, USA.
166
Life Sciences Institute, National University of Singapore, Singapore, Singapore.
167
NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, Singapore.
168
Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore.
169
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
170
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
171
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
172
Jackson Heart Study, School of Public Health, Jackson State University, Jackson, MS, USA.
173
State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
174
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
175
Division of Cancer Control and Population Sciences, UPMC Hillman Cancer, University of Pittsburgh, Pittsburgh, PA, USA.
176
Behavioral Epidemiology Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
177
Broad Institute of the Massachusetts Institute of Technology and Harvard University, Boston, MA, USA.
178
Nephrology, Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
179
Department of Genomics of Common Disease, Imperial College London, London, UK.
180
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
181
Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taipei, Taiwan.
182
Department of Ophthalmology, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany.
183
Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.
184
Department of Medicine, China Medical University, Taichung, Taiwan.
185
Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen RB, The Netherlands.
186
Department of Genetics, Harvard Medical School, Boston, MA, USA.
187
Geriatrics Section, Boston University Medical Center, Boston, MA, USA.
188
Institute of Physiology, University of Medicine Greifswald, Greifswald, Germany.
189
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen RB, The Netherlands.
190
Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
191
Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
192
Cardiovascular Health Research Unit, Epidemiology, Medicine and Health Services, University of Washington, Seattle, WA, USA.
193
Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
194
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
195
Dean's Office, University of Kentucky College of Public Health, Lexington, KY, USA.
196
Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands.
197
Cardiology, Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
198
Icahn School of Medicine at Mount Sinai, The Mindich Child Health and Development Institute, New York, NY, USA.
199
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
200
Harvard T. H. Chan School of Public Health, Department of Nutrition, Harvard University, Boston, MA, USA.
201
Department of Public Health & Clinical Medicine, Umeå University, Umeå, Västerbotten, Sweden.
202
Biostatistics, Preventive Medicine, University of Southern California, Los Angeles, CA, USA.

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.

PMID:
31127295
PMCID:
PMC6644157
[Available on 2020-08-01]
DOI:
10.1093/hmg/ddz070

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