BACKGROUND: Our aim was to identify genetic variants associated with blood pressure (BP) in childhood and adolescence. METHODS AND RESULTS: Genome-wide association study data from participating European ancestry cohorts of the Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium was meta-analyzed across 3 epochs; prepuberty (4-7 years), puberty (8-12 years), and postpuberty (13-20 years). Two novel loci were identified as having genome-wide associations with systolic BP across specific age epochs: rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor chromatin immunoprecipitation and 5'-C-phosphate-G-3' methylation site) during prepuberty (P=2.86×10(-8)) and rs872256 during puberty (P=8.67×10(-9)). Several single-nucleotide polymorphism clusters were also associated with childhood BP at P<5×10(-3). Using a P value threshold of <5×10(-3), we found some overlap in variants across the different age epochs within our study and between several single-nucleotide polymorphisms in any of the 3 epochs and adult BP-related single-nucleotide polymorphisms. CONCLUSIONS: Our results suggest that genetic determinants of BP act from childhood, develop over the lifecourse, and show some evidence of age-specific effects.
BACKGROUND: Our aim was to identify genetic variants associated with blood pressure (BP) in childhood and adolescence. METHODS AND RESULTS: Genome-wide association study data from participating European ancestry cohorts of the Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium was meta-analyzed across 3 epochs; prepuberty (4-7 years), puberty (8-12 years), and postpuberty (13-20 years). Two novel loci were identified as having genome-wide associations with systolic BP across specific age epochs: rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor chromatin immunoprecipitation and 5'-C-phosphate-G-3' methylation site) during prepuberty (P=2.86×10(-8)) and rs872256 during puberty (P=8.67×10(-9)). Several single-nucleotide polymorphism clusters were also associated with childhood BP at P<5×10(-3). Using a P value threshold of <5×10(-3), we found some overlap in variants across the different age epochs within our study and between several single-nucleotide polymorphisms in any of the 3 epochs and adult BP-related single-nucleotide polymorphisms. CONCLUSIONS: Our results suggest that genetic determinants of BP act from childhood, develop over the lifecourse, and show some evidence of age-specific effects.
Authors: Wolfgang Lieb; Henning Jansen; Christina Loley; Michael J Pencina; Christopher P Nelson; Christopher Newton-Cheh; Sekar Kathiresan; Muredach P Reilly; Themistocles L Assimes; Eric Boerwinkle; Alistair S Hall; Christian Hengstenberg; Reijo Laaksonen; Ruth McPherson; Unnur Thorsteinsdottir; Andreas Ziegler; Annette Peters; John R Thompson; Inke R König; Jeanette Erdmann; Nilesh J Samani; Ramachandran S Vasan; Heribert Schunkert Journal: Hypertension Date: 2013-03-11 Impact factor: 10.190
Authors: Ilana Talior-Volodarsky; Kim A Connelly; Pamma D Arora; Donald Gullberg; Christopher A McCulloch Journal: Cardiovasc Res Date: 2012-08-06 Impact factor: 10.787
Authors: B Xi; Y Shen; X Zhao; G R Chandak; H Cheng; D Hou; Y Li; J Ott; Y Zhang; X Wang; J Mi Journal: J Hum Hypertens Date: 2013-06-13 Impact factor: 3.012
Authors: Amy Milsted; Adam C Underwood; Jeff Dunmire; Helen L DelPuerto; Almir S Martins; Daniel L Ely; Monte E Turner Journal: J Hypertens Date: 2010-01 Impact factor: 4.844
Authors: Folkert W Asselbergs; Yiran Guo; Erik P A van Iperen; Suthesh Sivapalaratnam; Vinicius Tragante; Matthew B Lanktree; Leslie A Lange; Berta Almoguera; Yolande E Appelman; John Barnard; Jens Baumert; Amber L Beitelshees; Tushar R Bhangale; Yii-Der Ida Chen; Tom R Gaunt; Yan Gong; Jemma C Hopewell; Toby Johnson; Marcus E Kleber; Taimour Y Langaee; Mingyao Li; Yun R Li; Kiang Liu; Caitrin W McDonough; Matthijs F L Meijs; Rita P S Middelberg; Kiran Musunuru; Christopher P Nelson; Jeffery R O'Connell; Sandosh Padmanabhan; James S Pankow; Nathan Pankratz; Suzanne Rafelt; Ramakrishnan Rajagopalan; Simon P R Romaine; Nicholas J Schork; Jonathan Shaffer; Haiqing Shen; Erin N Smith; Sam E Tischfield; Peter J van der Most; Jana V van Vliet-Ostaptchouk; Niek Verweij; Kelly A Volcik; Li Zhang; Kent R Bailey; Kristian M Bailey; Florianne Bauer; Jolanda M A Boer; Peter S Braund; Amber Burt; Paul R Burton; Sarah G Buxbaum; Wei Chen; Rhonda M Cooper-Dehoff; L Adrienne Cupples; Jonas S deJong; Christian Delles; David Duggan; Myriam Fornage; Clement E Furlong; Nicole Glazer; John G Gums; Claire Hastie; Michael V Holmes; Thomas Illig; Susan A Kirkland; Mika Kivimaki; Ronald Klein; Barbara E Klein; Charles Kooperberg; Kandice Kottke-Marchant; Meena Kumari; Andrea Z LaCroix; Laya Mallela; Gurunathan Murugesan; Jose Ordovas; Willem H Ouwehand; Wendy S Post; Richa Saxena; Hubert Scharnagl; Pamela J Schreiner; Tina Shah; Denis C Shields; Daichi Shimbo; Sathanur R Srinivasan; Ronald P Stolk; Daniel I Swerdlow; Herman A Taylor; Eric J Topol; Elina Toskala; Joost L van Pelt; Jessica van Setten; Salim Yusuf; John C Whittaker; A H Zwinderman; Sonia S Anand; Anthony J Balmforth; Gerald S Berenson; Connie R Bezzina; Bernhard O Boehm; Eric Boerwinkle; Juan P Casas; Mark J Caulfield; Robert Clarke; John M Connell; Karen J Cruickshanks; Karina W Davidson; Ian N M Day; Paul I W de Bakker; Pieter A Doevendans; Anna F Dominiczak; Alistair S Hall; Catharina A Hartman; Christian Hengstenberg; Hans L Hillege; Marten H Hofker; Steve E Humphries; Gail P Jarvik; Julie A Johnson; Bernhard M Kaess; Sekar Kathiresan; Wolfgang Koenig; Debbie A Lawlor; Winfried März; Olle Melander; Braxton D Mitchell; Grant W Montgomery; Patricia B Munroe; Sarah S Murray; Stephen J Newhouse; N Charlotte Onland-Moret; Neil Poulter; Bruce Psaty; Susan Redline; Stephen S Rich; Jerome I Rotter; Heribert Schunkert; Peter Sever; Alan R Shuldiner; Roy L Silverstein; Alice Stanton; Barbara Thorand; Mieke D Trip; Michael Y Tsai; Pim van der Harst; Ellen van der Schoot; Yvonne T van der Schouw; W M Monique Verschuren; Hugh Watkins; Arthur A M Wilde; Bruce H R Wolffenbuttel; John B Whitfield; G Kees Hovingh; Christie M Ballantyne; Cisca Wijmenga; Muredach P Reilly; Nicholas G Martin; James G Wilson; Daniel J Rader; Nilesh J Samani; Alex P Reiner; Robert A Hegele; John J P Kastelein; Aroon D Hingorani; Philippa J Talmud; Hakon Hakonarson; Clara C Elbers; Brendan J Keating; Fotios Drenos Journal: Am J Hum Genet Date: 2012-10-11 Impact factor: 11.025
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Authors: Jochen Steppan; Huilei Wang; Yehudit Bergman; Marcel J Rauer; Siqi Tan; Sandeep Jandu; Kavitha Nandakumar; Sebastian Barreto-Ortiz; Robert N Cole; Tatiana N Boronina; Wanqu Zhu; Marc K Halushka; Steven S An; Dan E Berkowitz; Lakshmi Santhanam Journal: Am J Physiol Heart Circ Physiol Date: 2019-04-19 Impact factor: 4.733
Authors: Daiane Hemerich; Jiayi Pei; Magdalena Harakalova; Jessica van Setten; Sander Boymans; Bas J Boukens; Igor R Efimov; Michelle Michels; Jolanda van der Velden; Aryan Vink; Caroline Cheng; Pim van der Harst; Jason H Moore; Michal Mokry; Vinicius Tragante; Folkert W Asselbergs Journal: Circ Genom Precis Med Date: 2019-02
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Authors: Farah Ammous; Wei Zhao; Scott M Ratliff; Minjung Kho; Lulu Shang; Alana C Jones; Ninad S Chaudhary; Hemant K Tiwari; Marguerite R Irvin; Donna K Arnett; Thomas H Mosley; Lawrence F Bielak; Sharon L R Kardia; Xiang Zhou; Jennifer Smith Journal: Epigenetics Date: 2020-10-26 Impact factor: 4.528