Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.

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title = "Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.",
abstract = "Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.",
author = "Vinicius Tragante and Barnes, {Michael R} and Ganesh, {Santhi K} and Lanktree, {Matthew B} and Wei Guo and Nora Franceschini and Smith, {Erin N} and Toby Johnson and Holmes, {Michael V} and Sandosh Padmanabhan and Karczewski, {Konrad J} and Berta Almoguera and John Barnard and Jens Baumert and Chang, {Yen-Pei Christy} and Elbers, {Clara C} and Martin Farrall and Fischer, {Mary E} and Gaunt, {Tom R} and Gho, {Johannes M I H} and Christian Gieger and Anuj Goel and Yan Gong and Aaron Isaacs and Kleber, {Marcus E} and Leach, {Irene Mateo} and McDonough, {Caitrin W} and Meijs, {Matthijs F L} and Olle Melander and Nelson, {Christopher P} and Nolte, {Ilja M} and Nathan Pankratz and Price, {Tom S} and Jonathan Shaffer and Sonia Shah and Maciej Tomaszewski and {van der Most}, {Peter J} and {Van Iperen}, {Erik P A} and Vonk, {Judith M} and Kate Witkowska and Wong, {Caroline O L} and Li Zhang and Beitelshees, {Amber L} and Berenson, {Gerald S} and Bhatt, {Deepak L} and Morris Brown and Amber Burt and Cooper-Dehoff, {Rhonda M} and Connell, {John M} and Cruickshanks, {Karen J} and Curtis, {Sean P} and George Davey-Smith and Christian Delles and Gansevoort, {Ron T} and Xiuqing Guo and Shen Haiqing and Hastie, {Claire E} and Hofker, {Marten H} and Hovingh, {G Kees} and Kim, {Daniel S} and Kirkland, {Susan A} and Klein, {Barbara E} and Ronald Klein and Li, {Yun R} and Steffi Maiwald and Christopher Newton-Cheh and O'Brien, {Eoin T} and Onland-Moret, {N Charlotte} and Walter Palmas and Afshin Parsa and Penninx, {Brenda W} and Mary Pettinger and Vasan, {Ramachandran S} and Ranchalis, {Jane E} and {M Ridker}, Paul and Rose, {Lynda M} and Peter Sever and Daichi Shimbo and Laura Steele and Stolk, {Ronald P} and Barbara Thorand and Trip, {Mieke D} and {van Duijn}, {Cornelia M} and Verschuren, {W Monique} and Cisca Wijmenga and Sharon Wyatt and Young, {J Hunter} and Zwinderman, {Aeilko H} and Bezzina, {Connie R} and Eric Boerwinkle and Casas, {Juan P} and Caulfield, {Mark J} and Aravinda Chakravarti and Chasman, {Daniel I} and Davidson, {Karina W} and Doevendans, {Pieter A} and Dominiczak, {Anna F} and Fitzgerald, {Garret A} and Gums, {John G} and Myriam Fornage and Hakon Hakonarson and Indrani Halder and Hillege, {Hans L} and Thomas Illig and Jarvik, {Gail P} and Johnson, {Julie A} and Kastelein, {John J P} and Wolfgang Koenig and Meena Kumari and Winfried M{\"a}rz and Murray, {Sarah S} and O'Connell, {Jeffery R} and Oldehinkel, {Albertine J} and Pankow, {James S} and Rader, {Daniel J} and Susan Redline and Reilly, {Muredach P} and Schadt, {Eric E} and Kandice Kottke-Marchant and Harold Snieder and Michael Snyder and Stanton, {Alice V} and Tobin, {Martin D} and Uitterlinden, {Andr{\'e} G} and {van der Harst}, Pim and {van der Schouw}, {Yvonne T} and Samani, {Nilesh J} and Hugh Watkins and Johnson, {Andrew D} and Reiner, {Alex P} and Xiaofeng Zhu and {de Bakker}, {Paul I W} and Daniel Levy and Asselbergs, {Folkert W} and Munroe, {Patricia B} and Keating, {Brendan J}",
year = "2014",
doi = "10.1016/j.ajhg.2013.12.016",
language = "English",
volume = "94",
pages = "349--360",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "3",