@article{discovery1516363, month = {October}, pages = {1151--1161}, journal = {Nature Genetics}, note = {Copyright {\copyright} 2016 Nature America, Inc. All rights reserved.}, publisher = {NATURE PUBLISHING GROUP}, year = {2016}, volume = {48}, number = {10}, title = {Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension}, author = {Surendran, P and Drenos, F and Young, R and Warren, H and Cook, JP and Manning, AK and Grarup, N and Sim, X and Barnes, DR and Witkowska, K and Staley, JR and Tragante, V and Tukiainen, T and Yaghootkar, H and Masca, N and Freitag, DF and Ferreira, T and Giannakopoulou, O and Tinker, A and Harakalova, M and Mihailov, E and Liu, C and Kraja, AT and Nielsen, SF and Rasheed, A and Samue, M and Zhao, W and Bonnycastle, LL and Jackson, AU and Narisu, N and Swift, AJ and Southam, L and Marten, J and Huyghe, JR and Stancakova, A and Fava, C and Ohlsson, T and Matchan, A and Stirrups, KE and Bork-Jensen, J and Gjesing, AP and Kontto, J and Perola, M and Shaw-Hawkins, S and Havulinna, AS and Zhang, H and Donnelly, LA and Groves, CJ and Rayner, NW and Neville, MJ and Robertson, NR and Yiorkas, AM and Herzig, K-H and Kajantie, E and Zhang, W and Willems, SM and Lannfelt, L and Malerba, G and Soranzo, N and Trabetti, E and Verweij, N and Evangelou, E and Moayyeri, A and Vergnaud, A-C and Nelson, CP and Poveda, A and Varga, TV and Caslake, M and de Craen, AJM and Trompet, S and Luan, J and Scott, RA and Harris, SE and Liewald, DCM and Marioni, R and Menni, C and Farmaki, A-E and Hallmans, G and Renstrom, F and Huffman, JE and Hassinen, M and Burgess, S and Vasan, RS and Felix, JF and Uria-Nickelsen, M and Malarstign, A and Reilly, DF and Hoek, M and Vogt, TF and Lin, H and Lieb, W and Traylor, M and Markus, HS and Highland, HM and Justice, AE and Marouli, E and Lindstrom, J and Uusitupa, M and Komulainen, P and Lakka, TA and Rauramaa, R and Polasek, O and Rudan, I and Rolandsson, O and Franks, PW and Dedoussis, G and Spector, TD and Jousilahti, P and Mannisto, S and Deary, IJ and Starr, JM and Langenberg, C and Wareham, NJ and Brown, MJ and Dominiczak, AF and Connell, JM and Jukema, JW and Sattar, N and Ford, I and Packard, CJ and Esko, T and Magi, R and Metspalu, A and de Boer, RA and van der Meer, P and van der Harst, P and Gambaro, G and Ingelsson, E and Lind, L and de Bakker, PIW and Numans, ME and Brandslund, I and Christensen, C and Petersen, ERB and Korpi-Hyovalti, E and Oksa, H and Chambers, JC and Kooner, JS and Blakemore, AIF and Franks, S and Jarvelin, M-R and Husemoen, LL and Linneberg, A and Skaaby, T and Thuesen, B and Karpe, F and Tuomilehto, J and Doney, ASF and Morris, AD and Palmer, CNA and Holmen, OL and Hveem, K and Willer, CJ and Tuomi, T and Groop, L and Karajamaki, A and Palotie, A and Ripatti, S and Salomaa, V and Alam, DS and Majmnder, AAS and Di Angelantonio, E and Chowdhury, R and McCarthy, MI and Poulter, N and Stanton, AV and Sever, P and Amouyel, P and Arveiler, D and Blankenberg, S and Ferrieres, J and Kee, F and Kuulasmaa, K and Muller-Nurasyid, M and Veronesi, G and Virtamo, J and Deloukas, P and Elliott, P and Zeggini, E and Kathiresan, S and Melander, O and Kuusisto, J and Laakso, M and Padmanabhan, S and Porteous, DJ and Hayward, C and Scotland, G and Collins, FS and Mohlke, KL and Hansen, T and Pedersen, O and Boehnke, M and Stringham, HM and Frossard, P and Newton-Cheh, C and Tobin, MD and Nordestgaard, BG and Caulfield, MJ and Mahajan, A and Morris, AP and Tomaszewski, M and Samani, NJ and Saleheen, D and Asselbergs, FW and Lindgren, CM and Danesh, J and Wain, LV and Butterworth, AS and Howson, JMM and Munroe, PB}, url = {http://dx.doi.org/10.1038/ng.3654}, abstract = {High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used {\texttt{\char126}}155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects ({\ensuremath{>}}1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.}, issn = {1061-4036}, keywords = {Science \& Technology, Life Sciences \& Biomedicine, Genetics \& Heredity, Genome-wide Association, Gene-centric Array, Cardiovascular-disease, Aging Research, Plasma-levels, Risk-factors, Loci, Charge, Heart, Identification} }