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Effects of Long-Term Averaging of Quantitative Blood Pressure Traits on the Detection of Genetic Associations
Ganesh, Santhi K.1,2; Chasman, Daniel I.3,4; Larson, Martin G.5,6; Guo, Xiuqing7,8; Verwoert, Germain9,10; Bis, Joshua C.11; Gu, Xiangjun12; Smith, Albert V.13,14; Yang, Min-Lee1,2; Zhang, Yan15; Ehret, Georg16,17; Rose, Lynda M.3; Hwang, Shih-Jen5,18; Papanicolau, George J.19; Sijbrands, Eric J.10; Rice, Kenneth20; Eiriksdottir, Gudny13; Pihur, Vasyl16; Ridker, Paul M.3,4; Vasan, Ramachandran S.5,21,22; Newton-Cheh, Christopher23,24; Raffel, Leslie J.25; Amin, Najaf9; Rotter, Jerome I.7,8; Liu, Kiang26; Launer, Lenore J.27; Xu, Ming28; Caulfield, Mark29,30; Morrison, Alanna C.31; Johnson, Andrew D.5,32; Vaidya, Dhananjay33; Dehghan, Abbas9; Li, Guo11; Bouchard, Claude34; Harris, Tamara B.27; Zhang, He1,2; Boerwinkle, Eric31; Siscovick, David S.11,35; Gao, Wei28; Uitterlinden, Andre G.9,10,36; Rivadeneira, Fernando9,10; Hofman, Albert9; Willer, Cristen J.1,2; Franco, Oscar H.9; Huo, Yong15; Witteman, Jacqueline C. M.9; Munroe, Patricia B.29,30; Gudnason, Vilmundur13,14; Palmas, Walter37; van Duijn, Cornelia9,36,38; Fornage, Myriam12,39; Levy, Daniel5,18,40; Psaty, Bruce M.11,35,41; Chakravarti, Aravinda16; Global Blood Pressure Genetics Con
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Blood 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 x 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 IGEBP3). 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.

Subject Area临床医学
WOS HeadingsScience & Technology
WOS Research AreaGenetics & Heredity
WOS SubjectGenetics & Heredity
WOS IDWOS:000338904100004
Citation statistics
Cited Times:43[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Affiliation1.Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA
2.Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA
3.Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA
4.Harvard Univ, Sch Med, Boston, MA 02115 USA
5.NHLBI, Framingham Heart Study, Framingham, MA 01702 USA
6.Boston Univ, Dept Math, Boston, MA 02215 USA
7.Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA
8.Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA
9.Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3015 Rotterdam, Netherlands
10.Erasmus Univ, Med Ctr, Dept Internal Med, NL-3015 Rotterdam, Netherlands
11.Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA
12.Univ Texas Hlth Sci Ctr Houston, Res Ctr Human Genet, Brown Fdn Inst Mol Med, Houston, TX 77030 USA
13.Iceland Heart Assoc, IS-201 Kopavogur, Iceland
14.Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland
15.Peking Univ, Dept Cardiol, Hosp 1, Beijing 100034, Peoples R China
16.Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Sch Med, Baltimore, MD 21205 USA
17.Univ Hosp Geneva, Dept Specialties Internal Med, CH-1211 Geneva, Switzerland
18.NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA
19.NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA
20.Univ Washington, Dept Biostat, Seattle, WA 98195 USA
21.Boston Univ, Sch Med, Div Epidemiol, Boston, MA 02118 USA
22.Boston Univ, Sch Med, Div Cardiol, Dept Med, Boston, MA 02118 USA
23.Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA
24.Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA
25.Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA
26.Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA
27.Johns Hopkins Univ, Dept Med, Baltimore, MD 21287 USA
28.Columbia Univ, Dept Med, New York, NY 10032 USA
29.Boston Univ, Sch Med, Boston, MA 02118 USA
30.NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA
31.Peking Univ, Hosp 3, Dept Cardiol, Beijing 100191, Peoples R China
32.Queen Mary Univ London, Clin Pharmacol & Genome Ctr, William Harvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England
33.Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, London EC1M 6BQ, England
34.Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA
35.NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Bethesda, MD 20892 USA
36.Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA 70808 USA
37.Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA
38.Netherlands Genom Initiat, Netherlands Consortium Healthy Aging, NL-2593 The Hague, Netherlands
39.Netherlands Genom Initiat, Ctr Med Syst Biol, NL-2593 The Hague, Netherlands
40.Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX 77030 USA
41.Grp Hlth Cooperat Puget Sound, Group Hlth Res Inst, Seattle, WA 98101 USA
Recommended Citation
GB/T 7714
Ganesh, Santhi K.,Chasman, Daniel I.,Larson, Martin G.,et al. Effects of Long-Term Averaging of Quantitative Blood Pressure Traits on the Detection of Genetic Associations[J]. AMERICAN JOURNAL OF HUMAN GENETICS,2014,95(1):49-65.
APA Ganesh, Santhi K..,Chasman, Daniel I..,Larson, Martin G..,Guo, Xiuqing.,Verwoert, Germain.,...&Global Blood Pressure Genetics Con.(2014).Effects of Long-Term Averaging of Quantitative Blood Pressure Traits on the Detection of Genetic Associations.AMERICAN JOURNAL OF HUMAN GENETICS,95(1),49-65.
MLA Ganesh, Santhi K.,et al."Effects of Long-Term Averaging of Quantitative Blood Pressure Traits on the Detection of Genetic Associations".AMERICAN JOURNAL OF HUMAN GENETICS 95.1(2014):49-65.
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