University of Oulu

Surendran, P., Feofanova, E.V., Lahrouchi, N. et al. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals. Nat Genet 52, 1314–1332 (2020). https://doi.org/10.1038/s41588-020-00713-x

Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

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Author: Surendran, Praveen1,2,3,4,5; Feofanova, Elena, V6; Lahrouchi, Najim7,8,9;
Ntalla, Ioanna10; Karthikeyan, Savita1; Cook, James11; Chen, Lingyan1; Mifsud, Borbala10,12; Yao, Chen13,14; Kraja, Aldi T.15,16; Cartwright, James H.10; Hellwege, Jacklyn N.17; Giri, Ayush17,18; Tragante, Vinicius19,20; Thorleifsson, Gudmar20; Liu, Dajiang J.21; Prins, Bram P.1; Stewart, Isobel D.22; Cabrera, Claudia P.10,23; Eales, James M.24; Akbarov, Artur24; Auer, Paul L.25; Bielak, Lawrence F.26; Bis, Joshua C.27; Braithwaite, Vickie S.22,28,29; Brody, Jennifer A.27; Daw, E. Warwick15,16; Warren, Helen R.10,23; Drenos, Fotios30,31; Nielsen, Sune Fallgaard32; Faul, Jessica D.33; Fauman, Eric B.34; Fava, Cristiano35,36; Ferreira, Teresa37; Foley, Christopher N.1,38; Franceschini, Nora39; Gao, He40,41; Giannakopoulou, Olga10,42,43; Giulianini, Franco44; Gudbjartsson, Daniel F.20,45; Guo, Xiuqing46; Harris, Sarah E.47,48; Havulinna, Aki S.48,49; Helgadottir, Anna20; Huffman, Jennifer E.50; Hwang, Shih-Jen51,52,53; Kanoni, Stavroula10,54; Kontto, Jukka49; Larson, Martin G.52,53,55; Li-Gao, Ruifang56; Lindstrom, Jaana49; Lotta, Luca A.22; Lu, Yingchang57,58; Luan, Jian'an22; Mahajan, Anubha59,60; Malerba, Giovanni61; Masca, Nicholas G. D.62,63; Mei, Hao64; Menni, Cristina65; Mook-Kanamori, Dennis O.56,66; Mosen-Ansorena, David40; Muller-Nurasyid, Martina67,68,69; Pare, Guillaume70; Paul, Dirk S.1,2,71,72; Perola, Markus49,73; Poveda, Alaitz74; Rauramaa, Rainer75,76; Richard, Melissa77; Richardson, Tom G.78; Sepulveda, Nuno79,80; Sim, Xueling81,82,83; Smith, Albert, V81,84,85; Smith, Jennifer A.26,33; Staley, James R.1,78; Stanakova, Alena86,87; Sulem, Patrick20; Theriault, Sebastien88,89; Thorsteinsdottir, Unnur20,85; Trompet, Stella90,91; Varga, Tibor V.74; Edwards, Digna R. Velez92; Veronesi, Giovanni93; Weiss, Stefan94,95,96; Willems, Sara M.22; Yao, Jie46; Young, Robin97; Yu, Bing98; Zhang, Weihua40,41,99; Zhao, Jing-Hua1,22,71,72; Zhao, Wei26,100; Zhao, Wei26,100; Evangelou, Evangelos40,101; Aeschbacher, Stefanie102; Asllanaj, Eralda103,104; Blankenberg, Stefan96,105,106,107; Bonnycastle, Lori L.108; Bork-Jensen, Jette109; Brandslund, Ivan110,111; Braund, Peter S.62,63; Burgess, Stephen1,38,71,72; Cho, Kelly112,113,114; Christensen, Cramer115; Connell, John116; de Mutsert, Renee56; Dominiczak, Anna F.117; Dorr, Marcus96,118; Eiriksdottir, Gudny84; Farmaki, Aliki-Eleni119,120; Gaziano, J. Michael112,113,114; Grarup, Niels109; Grove, Megan L.6; Hallmans, Goran121; Hansen, Torben109; Have, Christian T.109; Heiss, Gerardo39; Jorgensen, Marit E.122; Jousilahti, Pekka49; Kajantie, Eero49,123,124,125,126,127; Kamat, Mihir1,71,72; Karajamaki, AnneMari128,129; Karpe, Fredrik60,130; Koistinen, Heikki A.49,131,132,133; Kovesdy, Csaba P.134; Kuulasmaa, Kari49; Laatikainen, Tiina49,87,135; Lannfelt, Lars136; Lee, I-Te137,138,139,140; Lee, Wen-Jane141,142; Linneberg, Allan143,144; Martin, Lisa W.145; Moitry, Marie146; Nadkarni, Girish57; Neville, Matt J.60,130; Palmer, Colin N. A.147; Papanicolaou, George J.148; Pedersen, Oluf109; Peters, James1,3,4,149; Poulter, Neil150; Rasheed, Asif151; Rasmussen, Katrine L.32; Rayner, N. William59,60; Magi, Reedik152; Renstrom, Frida74,121; Rettig, Rainer96,153; Rossouw, Jacques154; Schreiner, Pamela J.155; Sever, Peter S.156; Sigurdsson, Emil L.157,158; Skaaby, Tea159; Sun, Yan, V160; Sundstrom, Johan161; Thorgeirsson, Gudmundur20,85,162; Esko, Tonu152,163; Trabetti, Elisabetta61; Tsao, Philip S.164; Tuomi, Tiinamaija165,166,167,168; Turner, Stephen T.169; Tzoulaki, Ioanna40,101; Vaartjes, Ilonca170,171; Vergnaud, Anne-Claire40; Willer, Cristen J.172,173,174; Wilson, Peter W. F.175,176; Witte, Daniel R.177,178,179; Yonova-Doing, Ekaterina1; Zhang, He172; Aliya, Naheed180; Almgren, Peter181; Amouyel, Philippe182,183,184,185; Asselbergs, Folkert W.10,183,186; Barnes, Michael R.10,23; Blakemore, Alexandra, I30,187; Boehnke, Michael81,82; Bots, Michiel L.170,171; Bottinger, Erwin P.57; Buring, Julie E.44,188; Chambers, John C.40,41,99,189,190; Chen, Yii-Der Ida46; Chowdhury, Rajiv1,191; Conen, David88,192; Correa, Adolfo193; Smith, George Davey78; de Boer, Rudolf A.194; Deary, Ian J.47,195; Dedoussis, George119; Deloukas, Panos10,23,54,196; Di Angelantonio, Emanuele1,2,3,4,71,72,197; Elliott, Paul40,41,198,199,200; Felix, Stephan B.96,118; Ferrieres, Jean201,202; Ford, Ian203; Fornage, Myriam77,98; Franks, Paul W.74,121,97,204; Franks, Stephen205; Frossard, Philippe151; Gambaro, Giovanni206; Gaunt, Tom R.78; Groop, Leif167,207; Gudnason, Vilmundur84,85; Harris, Tamara B.208; Hayward, Caroline50; Hennig, Branwen J.29,209; Herzig, Karl-Heinz210,211; Ingelsson, Erik212,213,214,215; Tuomilehto, Jaakko49,216,217,218; Jarvelin, Marjo-Riitta30,40,41,219,220; Jukema, J. Wouter91,221; Kardia, Sharon L. R.26; Kee, Frank222; Kooner, Jaspal S.41,99,156,190; Kooperberg, Charles223; Launer, Lenore J.208; Lind, Lars161; Loos, Ruth J. F.57,224; Majumder, Abdulla Al Shafi225; Laakso, Markku87,135; McCarthy, Mark, I59,60,130,226,227; Melander, Olle36; Mohlke, Karen L.228; Murray, Alison D.229; Nordestgaard, Borge Gronne32; Orho-Melander, Marju36; Packard, Chris J.230; Padmanabhan, Sandosh231; Palmas, Walter232; Polasek, Ozren233; Porteous, David J.234,235; Prentice, Andrew M.29,236; Province, Michael A.15,16; Relton, Caroline L.78; Rice, Kenneth237; Ridker, Paul M.44,188; Rolandsson, Olov121; Rosendaal, Frits R.56; Rotter, Jerome, I46; Rudan, Igor238; Salomaa, Veikko49; Samani, Nilesh J.62,63; Sattar, Naveed117; Sheu, Wayne H-H137,138,239,240; Smith, Blair H.241; Soranzo, Nicole197,242,243; Spector, Timothy D.65; Starr, John M.47,244; Sebert, Sylvain220; Taylor, Kent D.46; Lakka, Timo A.75,76,245; Timpson, Nicholas J.78; Tobin, Martin D.63,246; van der Harst, Pim194,247,248,249; van der Meer, Peter194; Ramachandran, Vasan S.52,53,250; Verweij, Niek251; Virtamo, Jarmo49; Volker, Uwe94,95,96; Weir, David R.33; Zeggini, Eleftheria252,253,254,255; Charchar, Fadi J.62,256,257; Wareham, Nicholas J.22; Langenberg, Claudia22; Tomaszewski, Maciej24,258; Butterworth, Adam S.1,2,3,4,71,72,197; Caulfield, Mark J.10,23; Danesh, John1,2,3,4,71,72,197,242; Edwards, Todd L.17; Holm, Hilma20; Hung, Adriana M.259; Lindgren, Cecilia M.7,37,249; Liu, Chunyu260; Manning, Alisa K.114,261; Morris, Andrew P.11,249,262,263; Morrison, Alanna C.6; O'Donnell, Christopher J.264; Psaty, Bruce M.27,265,266,267; Saleheen, Danish1,151,268; Stefansson, Kari20,85; Boerwinkle, Eric6,51; Chasman, Daniel, I44,188; Levy, Daniel52,53,269; Newton-Cheh, Christopher7,8; Munroe, Patricia B.10,23; Howson, Joanna M. M.1,71,72,269,270
Organizations: 1Univ Cambridge, British Heart Fdn, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England.
2Univ Cambridge, British Heart Fdn, Ctr Res Excellence, Cambridge, England.
3Wellcome Genome Campus, Hlth Data Res UK Cambridge, Cambridge, England.
4Univ Cambridge, Cambridge, England.
5Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
6Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA.
7Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
8Massachusetts Gen Hosp, Ctr Genom Med, Cardiovasc Res Ctr, Boston, MA 02114 USA.
9Univ Amsterdam, Heart Ctr, Dept Clin & Expt Cardiol, Amsterdam Cardiovasc Sci Amsterdam,Amsterdam UMC, Amsterdam, Netherlands.
10Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.
11Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
12Hamad Bin Khalifa Univ, Coll Hlth & Life Sci, Doha, Qatar.
13Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
14NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
15Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
16Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA.
17Vanderbilt Univ, Med Ctr, Div Epidemiol,Dept Med,Inst Med & Publ Hlth, Vanderbilt Genet Inst,Tennessee Valley Healthcare, Nashville, TN USA.
18Vanderbilt Univ, Div Quantitat Sci, Dept Obstet & Gynecol, Vanderbilt Genet Inst,Med Ctr,Tennessee Valley He, Nashville, TN USA.
19Univ Utrecht, Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
20Amgen Inc, deCODE Genet, Reykjavik, Iceland.
21Penn State Coll Med, Inst Personalized Med, Hershey, PA USA.
22Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge, England.
23Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Ctr, London, England.
24Univ Manchester, Fac Med Biol & Hlth, Div Cardiovasc Sci, Manchester, Lancs, England.
25Univ Wisconsin, Joseph J Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA.
26Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
27Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
28Univ Cambridge, MRC Nutr & Bone Hlth Grp, Cambridge, England.
29London Sch Hyg & Trop Med, MRC Unit Gambia, Banjul, Gambia.
30Brunel Univ London, Coll Hlth & Life Sci, Dept Life Sci, London, England.
31UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England.
32Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark.
33Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA.
34Pfizer, Internal Med Res Unit, Cambridge, MA USA.
35Univ Verona, Dept Med, Verona, Italy.
36Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden.
37Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford, England.
38Univ Cambridge, MRC Biostat Unit, Cambridge, England.
39Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
40Imperial Coll London, MRC Ctr Environm & Hlth, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
41Imperial Coll London, Natl Inst Hlth Res NIHR, Imperial Biomed Res Ctr, London, England.
42Queen Mary Univ London, Ctr Genom Hlth, London, England.
43UCL, Div Psychiat, London, England.
44Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
45Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland.
46Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, Lundquist Inst Biomed Innovat, Torrance, CA 90509 USA.
47Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
48Univ Edinburgh, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.
49Finnish Inst Hlth & Welf, Dept Publ Hlth Solut, Helsinki, Finland.
50Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
51NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
52Boston Univ, Framingham, MA USA.
53Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
54Queen Mary Univ London, Ctr Genom Hlth, Life Sci, London, England.
55Boston Univ, Biostat Dept, Sch Publ Hlth, Boston, MA USA.
56Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands.
57Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med Mt Sinai, New York, NY 10029 USA.
58Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr, Dept Med,Sch Med,Div Epidemiol, Nashville, TN USA.
59Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.
60Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
61Univ Verona, Dept Neurosci Biomed & Movement Sci, Verona, Italy.
62Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.
63Natl Inst Hlth Res Leicester Biomed Res Ctr, Leicester, Leics, England.
64Univ Mississippi, Sch Populat Hlth, Dept Data Sci, Med Ctr, Jackson, MS USA.
65Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
66Leiden Univ, Dept Publ Hlth & Primary Care, Med Ctr, Leiden, Netherlands.
67Helmholtz Zentrum Munchen, Inst Genet Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany.
68Ludwig Maximilians Univ Munchen, Dept Med 1, Munich, Germany.
69LMU, Fac Med, IBE, Chair Genet Epidemiol, Munich, Germany.
70McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada.
71Univ Cambridge, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England.
72Cambridge Univ Hosp, Cambridge, England.
73Univ Helsinki, Fac Med, Clin & Mol Metab Res Program CAMM, Helsinki, Finland.
74Lund Univ, Skane Univ Hosp Malmo, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
75Kuopio Res Inst Exercise Med, Kuopio, Finland.
76Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland.
77Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Inst Mol Med, Houston, TX 77030 USA.
78Univ Bristol, Bristol Med Sch, Populat Hlth Sci, MRC Integrat Epidemiol Unit IEU, Bristol, Avon, England.
79London Sch Hyg & Trop Med, Fac Trop & Infect Dis, Dept Infect Biol, London, England.
80Univ Lisbon, Ctr Stat & Applicat, Lisbon, Portugal.
81Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
82Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
83Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
84Iceland Heart Assoc, Kopavogur, Iceland.
85Univ Iceland, Fac Med, Reykjavik, Iceland.
86Univ Eastern Finland, Kuopio, Finland.
87Kuopio Univ Hosp, Kuopio, Finland.
88McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
89Laval Univ, Dept Mol Biol Med Biochem & Pathol, Quebec City, PQ, Canada.
90Leiden Univ, Dept Gerontol & Geriatr, Med Ctr, Leiden, Netherlands.
91Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
92Vanderbilt Univ, Vanderbilt Genet Inst, Vanderbilt Epidemiol Ctr, Dept Obstet & Gynecol,Med Ctr,Tennessee Valley Hl, Nashville, TN USA.
93Univ Insubria, Res Ctr Epidemiol & Prevent Med, Dept Med & Surg, Varese, Italy.
94Univ Med, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
95Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany.
96DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
97Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
98Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.
99Ealing Gen Hosp, Dept Cardiol, Southall, Middx, England.
100Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
101Univ Ioannina, Dept Hyg & Epidemiol, Med Sch, Ioannina, Greece.
102Univ Hosp, Div Cardiol, Basel, Switzerland.
103Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
104Univ Med Ctr, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.
105Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany.
106Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany.
107German Ctr Cardiovasc Res DZHK, Partner Site Hamburg Kiel Lubeck, Hamburg, Germany.
108NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA.
109Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Fac Hlth & Med Sci, Copenhagen, Denmark.
110Lillebaelt Hosp, Dept Clin Biochem, Vejle, Denmark.
111Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark.
112VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA USA.
113Brigham & Womens Hosp, Dept Med, Div Aging, 75 Francis St, Boston, MA 02115 USA.
114Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
115Lillebaelt Hosp, Med Dept, Vejle, Denmark.
116Univ Dundee, Ninewells Hosp & Med Sch, Dundee, Scotland.
117Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
118Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.
119Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece.
120UCL, Inst Cardiovasc Sci, Dept Populat Sci & Expt Med, London, England.
121Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
122Steno Diabet Ctr, Gentofte, Denmark.
123Oulu Univ Hosp, PEDEGO Res Unit, MRC Oulu, Oulu, Finland.
124Univ Oulu, Oulu, Finland.
125Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
126Univ Helsinki, Hosp Children & Adolescents, Cent Hosp, Helsinki, Finland.
127Univ Helsinki, Helsinki, Finland.
128Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland.
129Vaasa Hlth Care Ctr, Diabet Ctr, Vaasa, Finland.
130Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
131Univ Helsinki, Dept Med, Helsinki, Finland.
132Univ Helsinki, Cent Hosp, Helsinki, Finland.
133Minerva Fdn, Helsinki, Finland.
134Memphis VA Med Ctr, Nephrol Sect, Memphis, TN USA.
135Univ Eastern Finland, Dept Med, Kuopio, Finland.
136Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden.
137Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrinol & Metab, Taichung, Taiwan.
138Natl Yang Ming Univ, Sch Med, Taipei, Taiwan.
139Chung Shan Med Univ, Sch Med, Taichung, Taiwan.
140Tunghai Univ, Coll Sci, Taichung, Taiwan.
141Taichung Vet Gen Hosp, Dept Med Res, Taichung, Taiwan.
142Tunghai Univ, Dept Social Work, Taichung, Taiwan.
143Bispebjerg & Frederiksberg Hosp, Ctr Clin Res & Prevent, Copenhagen, Denmark.
144Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
145George Washington Univ, Sch Med & Hlth Sci, Washington, DC USA.
146Univ Strasbourg, Strasbourg Univ Hosp, Dept Publ Hlth, Strasbourg, France.
147Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee, Scotland.
148NHLBI, Epidemiol Branch, Bldg 10, Bethesda, MD 20892 USA.
149Imperial Coll London, Dept Immunol & Inflammat, London, England.
150Imperial Coll London, Int Ctr Circulatory Hlth, London, England.
151Ctr Noncommunicable Dis, Karachi, Pakistan.
152Univ Tartu, Inst Genom, Tartu, Estonia.
153Univ Med Greifswald, Inst Physiol, Karlsburg, Germany.
154NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA.
155Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
156Imperial Coll London, Natl Heart & Lung Inst, London, England.
157Univ Iceland, Dept Family Med, Reykjavik, Iceland.
158Dev Ctr Primary Hlth Care Iceland, Reykjavik, Iceland.
159Bispebjerg & Frederiksberg Hosp, Ctr Clin Res & Dis Prevent, Copenhagen, Denmark.
160Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Dept Biomed Informat,Sch Med, Atlanta, GA 30322 USA.
161Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
162Natl Univ Hosp Iceland, Dept Internal Med, Div Cardiol, Landspitali, Reykjavik, Iceland.
163Broad Inst, Med & Populat Genet, Cambridge, MA USA.
164Stanford Univ, Div Cardiovasc Med, Sch Med, VA Palo Alto Hlth Care Syst, Stanford, CA USA.
165Folkhalsan Res Ctr, Helsinki, Finland.
166Helsinki Univ Cent Hosp, Dept Endocrinol, Helsinki, Finland.
167Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
168Univ Helsinki, Sweden Inst Mol Med Helsinki FIMM, Helsinki, Finland.
169Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA.
170Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
171Univ Utrecht, Univ Med Ctr Utrecht, Ctr Circulatory Hlth, Utrecht, Netherlands.
172Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
173Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
174Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
175Atlanta VAMC, Atlanta, GA USA.
176Emory Clin Cardiovasc Res Inst, Atlanta, GA USA.
177Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark.
178Danish Diabet Acad, Odense, Denmark.
179Steno Diabet Ctr Aarhus, Aarhus, Denmark.
180Int Ctr Diarrhoeal Dis Res Bangladesh Icddr B, Dhaka, Bangladesh.
181Lund Univ, Dept Med, Malmo, Sweden.
182Univ Lille, U1167 RID AGE Facteurs Risque & Terminants Mol Cu, Lille, France.
183INSERM, U1167, Lille, France.
184CHU Lille, U1167, Lille, France.
185Inst Pasteur, U1167, Lille, France.
186UCL, Inst Hlth Informat, Hlth Data Res UK, London, England.
187Imperial Coll London, Sect Invest Med, Hammersmith Hosp Campus,Du Cane Rd, London, England.
188Harvard Med Sch, Boston, MA 02115 USA.
189Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore.
190Imperial Coll Healthcare NHS Trust, London, England.
191Ctr Noncommunicable Dis Res CNCR, Dhaka, Bangladesh.
192Cardiovasc Res Inst Basel, Basel, Switzerland.
193Univ Mississippi, Med Ctr, Dept Med, Jackson Heart Study, Jackson, MS 39216 USA.
194Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
195Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland.
196King Abdulaziz Univ, Princess Jawhara Brah Ctr Excellence Res Heredita, Jeddah, Saudi Arabia.
197Univ Cambridge, Natl Inst Hlth Res NIHR, Blood & Transplant Res Unit BTRU Donor Hlth & Gen, Cambridge, England.
198Imperial Coll London, Hlth Data Res UK London, London, England.
199Imperial Coll London, Dementia Res Inst, UKDRI, London, England.
200Imperial Coll London, British Heart Fdn BHF Ctr Res Excellence, London, England.
201Toulouse Univ Hosp, Dept Cardiol, Toulouse, France.
202Toulouse Univ Hosp, INSERM UMR 1027, Dept Epidemiol, Toulouse, France.
203Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
204Univ Oxford, Oxford Ctr Diabet, Radcliff Dept Med, Oxford, England.
205Imperial Coll London, Inst Reprod & Dev Biol, London, England.
206Univ Verona, Dept Med, Div Nephrol, Verona, Italy.
207Univ Helsinki, Inst Mol Med Helsinki FIMM, Helsinki, Finland.
208NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
209Wellcome Trust Res Labs, London, England.
210Univ Oulu, Univ Hosp Oulu, Med Res Ctr MRC, Inst Biomed, Oulu, Finland.
211Poznan Univ Med Sci, Dept Gastroenterol & Metab, Poznan, Poland.
212Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA USA.
213Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden.
214Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
215Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
216Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.
217King Abdulaziz Univ, Saudi Diabet Res Grp, Jeddah, Saudi Arabia.
218Natl Inst Publ Hlth, Madrid, Spain.
219Oulu Univ Hosp, Unit Primary Care, Oulu, Finland.
220Univ Oulu, Fac Med, Ctr Life Course Hlth Res, Oulu, Finland.
221Netherlands Heart Inst, Utrecht, Netherlands.
222Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
223Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
224Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
225Natl Inst Cardiovasc Dis, Dhaka, Bangladesh.
226Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
227Genentech Inc, 460 Point San Bruno Blvd, San Francisco, CA 94080 USA.
228Univ Aberdeen, Aberdeen Biomed Imaging Ctr, Inst Med Sci, Aberdeen, Scotland.
229Univ Glasgow, Glasgow, Lanark, Scotland.
230Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
231Columbia Univ, Dept Med, Med Ctr, New York, NY USA.
232Univ Split, Dept Publ Hlth, Sch Med, Split, Croatia.
233Univ Edinburgh, Western Gen Hosp, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
234Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Dept Psychol, Edinburgh, Midlothian, Scotland.
235London Sch Hyg & Trop Med, MRC Int Nutr Grp, Keppel St, London, England.
236Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
237Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
238Natl Def Med Ctr, Sch Med, Taipei, Taiwan.
239Natl Chung Hsing Univ, Inst Med Technol, Taichung, Taiwan.
240Univ Dundee, Ninewells Hosp & Med Sch, Div Populat Hlth & Genom, Dundee, Scotland.
241Wellcome Sanger Inst, Dept Human Genet, Wellcome Genome Campus, Cambridge, England.
242Univ Cambridge, Dept Haematol, Cambridge, England.
243Univ Edinburgh, Alzheimer Scotland Res Ctr, Edinburgh, Midlothian, Scotland.
244Univ Eastern Finland, Inst Biomed Physiol, Kuopio, Finland.
245Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
246Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
247ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.
248Boston Univ, Sch Med, Boston, MA 02118 USA.
249Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA.
250Univ Med Ctr Groningen, Groningen, Netherlands.
251Wellcome Sanger Inst, Wellcome Genome Campus, Cambridge, England.
252Helmholtz Zentrum Munchen, Inst Translat Genom, German Res Ctr Environm Hlth, Neuherberg, Germany.
253Tech Univ Munich, TUM Sch Med, Munich, Germany.
254Klinikum Rechts Der Isar, Munich, Germany.
255Federat Univ Australia, Hlth Innovat & Transformat Ctr, Ballarat, Vic, Australia.
256Univ Melbourne, Dept Physiol, Melbourne, Vic, Australia.
257Manchester Univ NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Div Med, Manchester, Lancs, England.
258Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Kidney Dis,Dept Med, VA Tennessee Valley Healthcare Syst,Div Nephrol &, Nashville, TN USA.
259Univ Oxford, Wellcome Ctr Human Genet, Oxford, England.
260Massachusetts Gen Hosp, Mongan Inst, Clin & Translat Epidemiol Unit, Boston, MA USA.
261Univ Manchester, Ctr Genet & Genom Versus Arthrit, Ctr Musculoskeletal Res, Manchester, Lancs, England.
262Harvard Med Sch, Brigham & Womens Hosp, Sect Cardiol, VA Boston Healthcare, Boston, MA 02115 USA.
263Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
264Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
265Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
266Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
267Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
268Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
269Novo Nordisk Res Ctr Oxford, Dept Genet, Oxford, England.
270Novo Nordisk Ltd, Novo Nordisk Res Ctr Oxford, Oxford, England.
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 3.6 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021082343904
Language: English
Published: Springer Nature, 2020
Publish Date: 2021-08-23
Description:

Abstract

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 x 10(⁻⁸)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.

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A Publisher Correction to this article was published on 16 March 2021.

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Series: Nature genetics
ISSN: 1061-4036
ISSN-E: 1546-1718
ISSN-L: 1061-4036
Volume: 52
Issue: 12
Pages: 1314 - 1332
DOI: 10.1038/s41588-020-00713-x
OADOI: https://oadoi.org/10.1038/s41588-020-00713-x
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
Subjects:
Funding: P. Surendran is supported by a Rutherford Fund Fellowship from the Medical Research Council (grant no. MR/S003746/1). N.L. is supported by the Foundation "De Drie Lichten' in the Netherlands and the Netherlands Cardiovascular Research Initiative, an initiative supported by the Dutch Heart Foundation (CVON2012-10 PREDICT and CVON2018-30 PREDICT2). S. Karthikeyan and B.P. are funded by a BHF Programme Grant Genetic Epidemiology of Cancer (MAGEC) Training Program (T32CA160056, PI X.-O.S.). N.F. is supported by the National Institute of Health awards HL140385, MD012765 and DK117445. E.Y.-D. was funded by the Isaac Newton Trust/Wellcome Trust ISSF/University of Cambridge Joint Research Grants Scheme. R.C. is funded by a Medical Research Council-Newton Project Grant to study genetic risk factors of cardiovascular disease among Southeast Asians and a UK Research and Innovation-Global Challenges Research Fund Project Grant (CAPABLE) to study risk factors of non-communicable diseases in Bangladesh. F.W.A. is supported by UCL Hospitals NIHR Biomedical Research Centre. P.D. was supported by the British Heart Foundation (BHF) grant RG/14/5/30893. R.J.F.L. is funded by grants R01DK110113, U01HG007417, R01DK101855 and R01DK107786. C.H. is supported by MRC University Unit Programme grants MC_UU_00007/10 (QTL in Health and Disease) and MC_PC_U127592696. M.I.M* was a Wellcome Senior Investigator (098381; 212259) and an NIHR Senior Investigator Biomedical Research Centre (BRC) and by the Wellcome Trust (090532, 106130, 098381, 203141 and 212259). The views expressed by C.Y., S.H., J.R. and G.J.P. are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the US Department of Health and Human Services. T.F.* is supported by the NIHR Biomedical Research Centre in Oxford. M.J. is supported by PrevMetSyn/SALVE, H2020 DynaHEALTH action (grant agreement 633595), EU H2020-HCO-2004 iHEALTH Action (grant agreement 643774). K.-H.H. is supported by PrevMetSyn/SALVE, H2020 DynaHEALTH action (grant agreement 633595) and EU H2020-HCO-2004 iHEALTH Action (grant agreement 643774). N.S. is supported by the British Heart Foundation Research Excellence Award Health Data Research UK. N.F. is supported by NIH awards R01-DK117445, R01-MD012765 and R21-HL140385. G.D.S., T.R.G. and C.L.R. work in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council award from the Fonds de Recherche du Quebec-Sante (FRQS). M.T. is supported by the BHF (PG/17/35/33001 and PG/19/16/34270) and Kidney Research UK (RP_017_20180302). V.S.R. is supported in part by the Evans Medical Foundation and the Jay and Louis Coffman Endowment from the Department of Medicine, Boston University School of Medicine. J.D.* holds a British Heart Foundation Professorship and a National Institute for Health Research Senior Investigator Award. C.M.L.* is supported by the Li Ka Shing Foundation, WT-SSI/John Fell funds and by the NIHR Biomedical Research Centre, by Widenlife and the National Institutes of Health (5P50HD028138-27). J.M.M.H.* was funded by the NIHR (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust).; r *The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Full acknowledgements and full lists of consortia members are provided in the Supplementary Note.
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
(643774) iHealth-T2D - Family-based intervention to improve healthy lifestyle and prevent Type 2 Diabetes amongst South Asians with central obesity and prediabetes
Copyright information: © The Author(s), under exclusive licence to Springer Nature America, Inc. 2020, corrected publication 2021. This is a post-peer-review, pre-copyedit version of an article published in Nat Genet. The final authenticated version is available online at https://doi.org/10.1038/s41588-020-00713-x.