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Am J Hum Genet. 2014 Jul 3;95(1):49-65. doi: 10.1016/j.ajhg.2014.06.002. Epub 2014 Jun 26.

Effects of long-term averaging of quantitative blood pressure traits on the detection of genetic associations.

Collaborators (159)

Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L, Najjar SS, Zhao JH, Heath SC, Eyheramendy S, Papadakis K, Voight BF, Scott LJ, Zhang F, Farrall M, Tanaka T, Wallace C, Chambers JC, Khaw KT, Nilsson P, van der Harst P, Polidoro S, Grobbee DE, Onland-Moret NC, Bots ML, Wain LV, Elliott KS, Teumer A, Luan J, Lucas G, Kuusisto J, Burton PR, Hadley D, McArdle WL, Brown M, Dominiczak A, Newhouse SJ, Samani NJ, Webster J, Zeggini E, Beckmann JS, Bergmann S, Lim N, Song K, Vollenweider P, Waeber G, Waterworth DM, Yuan X, Groop L, Orho-Melander M, Allione A, Di Gregorio A, Guarrera S, Panico S, Ricceri F, Romanazzi V, Sacerdote C, Vineis P, Barroso I, Sandhu MS, Luben RN, Crawford GJ, Jousilahti P, Perola M, Boehnke M, Bonnycastle LL, Collins FS, Jackson AU, Mohlke KL, Stringham HM, Valle TT, Willer CJ, Bergman RN, Morken MA, Döring A, Gieger C, Illig T, Meitinger T, Org E, Pfeufer A, Wichmann HE, Kathiresan S, Marrugat J, O'Donnell CJ, Schwartz SM, Siscovick DS, Subirana I, Freimer NB, Hartikainen AL, McCarthy MI, O'Reilly PF, Peltonen L, Pouta A, de Jong PE, Snieder H, van Gilst WH, Clarke R, Goel A, Hamsten A, Peden JF, Seedorf U, Syvänen AC, Tognoni G, Lakatta EG, Sanna S, Scheet P, Schlessinger D, Scuteri A, Dörr M, Ernst F, Felix SB, Homuth G, Lorbeer R, Reffelmann T, Rettig R, Völker U, Galan P, Gut IG, Hercberg S, Lathrop GM, Zeleneka D, Deloukas P, Soranzo N, Williams FM, Zhai G, Salomaa V, Laakso M, Elosua R, Forouhi NG, Völzke H, Uiterwaal CS, van der Schouw YT, Numans ME, Matullo G, Navis G, Berglund G, Bingham SA, Kooner JS, Paterson AD, Connell JM, Bandinelli S, Ferrucci L, Watkins H, Spector TD, Tuomilehto J, Altshuler D, Strachan DP, Laan M, Meneton P, Wareham NJ, Uda M, Jarvelin MR, Mooser V, Melander O, Loos RJ, Elliott P, Abecasis GR, Caulfield M, Munroe PB.

Author information

1
Departments of Internal Medicine and Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: sganesh@umich.edu.
2
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA; Harvard Medical School, Boston MA, 02115, USA.
3
Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA 01702, USA; Department of Mathematics, Boston University, Boston, MA 02215, USA.
4
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Torrance, CA 90502, USA; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
5
Department of Epidemiology, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 Rotterdam, the Netherlands.
6
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
7
Research Center for Human Genetics, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
8
Icelandic Heart Association, 201 Kopavogur, Iceland; Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
9
Departments of Internal Medicine and Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
10
Department of Cardiology, Peking University First Hospital, Beijing 100034, China.
11
Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns-Hopkins University School of Medicine, Baltimore, MD 21205, USA; Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospitals, 1211 Geneva, Switzerland.
12
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA.
13
Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA 01702, USA; Center for Population Studies, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
14
Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
15
Department of Internal Medicine, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 Rotterdam, the Netherlands.
16
Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
17
Icelandic Heart Association, 201 Kopavogur, Iceland.
18
Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns-Hopkins University School of Medicine, Baltimore, MD 21205, USA.
19
Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA 01702, USA; Divisions of Epidemiology and Cardiology, Department of Medicine, Boston University School for Medicine, Boston, MA 02118, USA.
20
Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
21
Medical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
22
Department of Epidemiology, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 Rotterdam, the Netherlands.
23
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
24
Laboratory of Epidemiology and Population Science, National Institute on Aging, Bethesda, MD 20892, USA.
25
Department of Cardiology, Peking University Third Hospital, Beijing 100191, China.
26
Clinical Pharmacology and the Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK; NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London EC1M 6BQ, UK.
27
Human Genetics Center, University of Texas Health Sciences Center at Houston, Houston, TX 77030, USA.
28
Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA 01702, USA; Cardiovascular Epidemiology and Human Genomics Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 02892, USA.
29
Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
30
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
31
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA; Department of Epidemiology, University of Washington, Seattle, WA 98101, USA.
32
Department of Epidemiology, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 Rotterdam, the Netherlands; Netherlands Consortium for Healthy Aging, Netherlands Genomics Initiative, 2593 the Hague, the Netherlands.
33
Department of Medicine, Columbia University, New York, NY 10032, USA.
34
Department of Epidemiology, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 Rotterdam, the Netherlands; Netherlands Consortium for Healthy Aging, Netherlands Genomics Initiative, 2593 the Hague, the Netherlands; Centre for Medical Systems Biology, Netherlands Genomics Initiative, 2593 the Hague, the Netherlands.
35
Research Center for Human Genetics, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
36
Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA 01702, USA; Center for Population Studies, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA; Boston University School of Medicine, Boston, MA 02118, USA.
37
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA; Department of Epidemiology, University of Washington, Seattle, WA 98101, USA; Group Health Research Institute, Group Health Cooperative, Seattle, WA 98101, USA.
38
Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns-Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: aravinda@jhmi.edu.

Abstract

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 × 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.

PMID:
24975945
PMCID:
PMC4085637
DOI:
10.1016/j.ajhg.2014.06.002
[Indexed for MEDLINE]
Free PMC Article

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