Genome-wide association study identifies eight loci associated with blood pressure

Title: Genome-wide association study identifies eight loci associated with blood pressure
Authors: 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, K-T
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
Doering, 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, A-L
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
Syvanen, A-C
Tognoni, G
Lakatta, EG
Sanna, S
Scheet, P
Schlessinger, D
Scuteri, A
Doerr, M
Ernst, F
Felix, SB
Homuth, G
Lorbeer, R
Reffelmann, T
Rettig, R
Voelker, U
Galan, P
Gut, IG
Hercberg, S
Lathrop, GM
Zelenika, D
Deloukas, P
Soranzo, N
Williams, FM
Zhai, G
Salomaa, V
Laakso, M
Elosua, R
Forouhi, NG
Volzke, H
Uiterwaal, CS
Van der Schouw, YT
Numans, ME
Matullo, G
Navis, G
Berglund, G
Bingham, SA
Kooner, JS
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, M-R
Mooser, V
Melander, O
Loos, RJF
Elliott, P
Abecasis, GR
Caulfield, M
Munroe, PB
Item Type: Journal Article
Abstract: Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10−24), CYP1A2 (P = 1 × 10−23), FGF5 (P = 1 × 10−21), SH2B3 (P = 3 × 10−18), MTHFR (P = 2 × 10−13), c10orf107 (P = 1 × 10−9), ZNF652 (P = 5 × 10−9) and PLCD3 (P = 1 × 10−8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
Issue Date: 10-May-2009
Date of Acceptance: 27-Feb-2009
URI: http://hdl.handle.net/10044/1/72539
DOI: https://doi.org/10.1038/ng.361
ISSN: 1061-4036
Publisher: Nature Research
Start Page: 666
End Page: 676
Journal / Book Title: Nature Genetics
Volume: 41
Issue: 6
Copyright Statement: © 2009 Springer-Nature. The final publication is available at Springer via https://doi.org/10.1038/ng.361
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: G0801056B
G0801056
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
METHYLENETETRAHYDROFOLATE REDUCTASE GENE
LOW-RENIN HYPERTENSION
COMMON VARIANTS
CELL-DIFFERENTIATION
BARTTERS-SYNDROME
PUBLIC-HEALTH
RISK
POLYMORPHISM
POPULATION
MUTATIONS
Blood Pressure
Cardiovascular Diseases
Chromosome Mapping
Cytochrome P-450 CYP1A2
DNA-Binding Proteins
Diastole
Europe
European Continental Ancestry Group
Fibroblast Growth Factor 5
Genetic Variation
Genome-Wide Association Study
Humans
India
Methylenetetrahydrofolate Reductase (NADPH2)
Open Reading Frames
Phospholipase C delta
Polymorphism, Single Nucleotide
Proteins
Steroid 17-alpha-Hydroxylase
Systole
Wellcome Trust Case Control Consortium
Humans
Cardiovascular Diseases
Cytochrome P-450 CYP1A2
Steroid 17-alpha-Hydroxylase
Methylenetetrahydrofolate Reductase (NADPH2)
Proteins
DNA-Binding Proteins
Chromosome Mapping
Blood Pressure
Diastole
Systole
Polymorphism, Single Nucleotide
Open Reading Frames
European Continental Ancestry Group
India
Europe
Fibroblast Growth Factor 5
Phospholipase C delta
Genetic Variation
Genome-Wide Association Study
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
METHYLENETETRAHYDROFOLATE REDUCTASE GENE
LOW-RENIN HYPERTENSION
COMMON VARIANTS
CELL-DIFFERENTIATION
BARTTERS-SYNDROME
PUBLIC-HEALTH
RISK
POLYMORPHISM
POPULATION
MUTATIONS
Developmental Biology
11 Medical and Health Sciences
06 Biological Sciences
Publication Status: Published
Online Publication Date: 2009-05-10
Appears in Collections:National Heart and Lung Institute
Epidemiology, Public Health and Primary Care



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