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Get Free AccessBlood pressure (BP) is a heritable, quantitative trait with intraindividual variability and susceptibility to measurement error. Genetic studies of BP generally use single-visit measurements and thus cannot remove variability occurring over months or years. We leveraged the idea that averaging BP measured across time would improve phenotypic accuracy and thereby increase statistical power to detect genetic associations. We studied systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) averaged over multiple years in 46,629 individuals of European ancestry. We identified 39 trait-variant associations across 19 independent loci (p < 5 × 10−8); five associations (in four loci) uniquely identified by our LTA analyses included those of SBP and MAP at 2p23 (rs1275988, near KCNK3), DBP at 2q11.2 (rs7599598, in FER1L5), and PP at 6p21 (rs10948071, near CRIP3) and 7p13 (rs2949837, near IGFBP3). Replication analyses conducted in cohorts with single-visit BP data showed positive replication of associations and a nominal association (p < 0.05). We estimated a 20% gain in statistical power with long-term average (LTA) as compared to single-visit BP association studies. Using LTA analysis, we identified genetic loci influencing BP. LTA might be one way of increasing the power of genetic associations for continuous traits in extant samples for other phenotypes that are measured serially over time.
Santhi K. Ganesh, Daniel I. Chasman, Martin G. Larson, Xiuqing Guo, Germain Verwoert, Joshua C. Bis, Xiangjun Gu, Albert V. Smith, Min‐Lee Yang, Yan Zhang, Georg Ehret, Lynda M. Rose, Shih‐Jen Hwang, George J. Papanicolau, Eric J.G. Sijbrands, Kenneth Rice, Guðný Eiríksdóttir, Vasyl Pihur, Paul M. Ridker, Ramachandran S. Vasan, Christopher Newton‐Cheh, Leslie J. Raffel, Najaf Amin, Jerome I. Rotter, Kiang Liu, Lenore J. Launer, Ming Xu, Mark J. Caulfield, Alanna C. Morrison, Andrew D. Johnson, Dhananjay Vaidya, Abbas Dehghan, Guo Li, Claude Bouchard, Tamara B. Harris, He Zhang, Eric Boerwinkle, David S. Siscovick, Wei Gao, André G. Uitterlinden, Fernando Rivadeneira, Albert Hofman, Cristen J. Willer, Oscar H. Franco, Yong Huo, Jacqueline C.M. Witteman, Patricia B. Munroe, Vilmundur Guðnason, Walter Palmas, Cornelia M. van Duijn, Myriam Fornage, Daniel Levy, Bruce M. Psaty, Aravinda Chakravarti, Christopher Newton‐Cheh, Toby Johnson, Vesela Gateva, Martin D. Tobin, Murielle Bochud, Lachlan Coin, Samer S. Najjar, Jing Hua Zhao, Simon Heath, S. Eyheramendy, Konstantinos A. Papadakis, Benjamin F. Voight, Laura J. Scott, Feng Zhang, Martin Farrall, Toshiko Tanaka, Chris Wallace, John C. Chambers, Kay‐Tee Khaw, Peter Nilsson, Pim van der Harst, Silvia Polidoro, Diederick E. Grobbee, N. Charlotte Onland‐Moret, Michiel L. Bots, Louise V. Wain, Katherine S. Elliott, Alexander Teumer, Jian’an Luan, Gavin Lucas, Johanna Kuusisto, Paul R. Burton, David Hadley, Wendy L. McArdle, Matthew A. Brown, Anna F. Dominiczak, Stephen Newhouse, Nilesh J. Samani, John Webster, Eleftheria Zeggini, J. Beckmann, Sven Bergmann, Noha Lim, Kijoung Song, Péter Vollenweider, Gérard Waeber (2014). Effects of Long-Term Averaging of Quantitative Blood Pressure Traits on the Detection of Genetic Associations. The American Journal of Human Genetics, 95(1), pp. 49-65, DOI: 10.1016/j.ajhg.2014.06.002.
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Type
Article
Year
2014
Authors
100
Datasets
0
Total Files
0
Language
English
Journal
The American Journal of Human Genetics
DOI
10.1016/j.ajhg.2014.06.002
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