Genome-wide association study identifies eight loci associated with blood pressure
Christopher Newton-Cheh and colleagues report a genome-wide association study for blood pressure traits as part of the Global BPgen consortium. They report eight loci with replicated association to systolic and/or diastolic blood pressure, with each also showing association to hypertension. Elevated...
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| Published in | Nature genetics Vol. 41; no. 6; pp. 666 - 676 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.06.2009
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Christopher Newton-Cheh and colleagues report a genome-wide association study for blood pressure traits as part of the Global BPgen consortium. They report eight loci with replicated association to systolic and/or diastolic blood pressure, with each also showing association to hypertension.
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. |
|---|---|
| AbstractList | 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. 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 x [10.sup.-24]), CYP1A2 (P = 1 x [10.sup.-23]), FGF5 (P = 1 x [10.sup.-21]), SH2B3 (P = 3 x [10.sup.-18]), MTHFR (P = 2 x [10.sup.-13]), c10orf107 (P = 1 x [10.sup.-9]), ZNF652 (P = 5 x [10.sup.-9]) and PLCD3 (P = 1 x [10.sup.-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. 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 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 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. 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^sup -24^), CYP1A2 (P = 1 × 10^sup -23^), FGF5 (P = 1 × 10^sup -21^), SH2B3 (P = 3 × 10^sup -18^), MTHFR (P = 2 × 10^sup -13^), c10orf107 (P = 1 × 10^sup -9^), ZNF652 (P = 5 × 10^sup -9^) and PLCD3 (P = 1 × 10^sup -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. [PUBLICATION 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.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. 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. 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 [less] 71,225 European ancestry, N [less] 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 [math] 10 super(-24)), CYP1A2 (P = 1 [math] 10 super(-23)), FGF5 (P = 1 [math] 10 super(- 21)), SH2B3 (P = 3 [math] 10 super(-18)), MTHFR (P = 2 [math] 10 super(-13)), c10orf107 (P = 1 [math] 10 super(-9)), ZNF652 (P = 5 [math] 10 super(-9)) and PLCD3 (P = 1 [math] 10 super(-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. Christopher Newton-Cheh and colleagues report a genome-wide association study for blood pressure traits as part of the Global BPgen consortium. They report eight loci with replicated association to systolic and/or diastolic blood pressure, with each also showing association to hypertension. 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. |
| Audience | Academic |
| Author | Döring, Angela Seedorf, Udo Coin, Lachlan Mohlke, Karen L Luan, Jian'an Jousilahti, Pekka Freimer, Nelson B Onland-Moret, N Charlotte Stringham, Heather M Kooner, Jaspal S Lakatta, Edward G Sanna, Serena Lorbeer, Roberto McCarthy, Mark I Peden, John F Elosua, Roberto Pfeufer, Arne O'Reilly, Paul F Farrall, Martin Khaw, Kay-Tee Munroe, Patricia B Papadakis, Konstantinos Elliott, Paul Dörr, Marcus Samani, Nilesh J Ricceri, Fulvio Subirana, Isaac van der Schouw, Yvonne T van Gilst, Wiek H Numans, Mattijs E Rettig, Rainer Laan, Maris Strachan, David P Vollenweider, Peter Sacerdote, Carlotta Burton, Paul R Marrugat, Jaume Forouhi, Nita G Panico, Salvatore Soranzo, Nicole Wichmann, H Erich van der Harst, Pim Crawford, Gabriel J Johnson, Toby Sandhu, Manjinder S Zelenika, Diana Orho-Melander, Marju O'Donnell, Christopher J Gateva, Vesela Tobin, Martin D Barroso, Inês Matullo, Giuseppe Newhouse, Stephen J Bingham, Sheila A Bochud, Murielle Berglund, Göran Voight, Benjamin F Caulfield, Mark Chambers, John C Newton-Cheh, Christopher Perola, Markus Willer, |
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organization: National Heart and Lung Institute, Imperial College London – sequence: 141 givenname: Stefania surname: Bandinelli fullname: Bandinelli, Stefania organization: Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze (ASF) – sequence: 143 givenname: Hugh surname: Watkins fullname: Watkins, Hugh organization: Department of Cardiovascular Medicine, University of Oxford, The Wellcome Trust Centre for Human Genetics – sequence: 145 givenname: Jaakko surname: Tuomilehto fullname: Tuomilehto, Jaakko organization: Department of Epidemiology and Health Promotion, Diabetes Unit, National Public Health Institute, Department of Public Health, University of Helsinki, South Ostrobothnia Central Hospital – sequence: 146 givenname: David surname: Altshuler fullname: Altshuler, David organization: Center for Human Genetic Research, Massachusetts General Hospital, Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Department of Medicine and Department of Genetics, Harvard Medical School, Diabetes Unit, Massachusetts General Hospital – sequence: 148 givenname: Maris surname: Laan fullname: Laan, Maris organization: Institute of Molecular and Cell Biology, University of Tartu – sequence: 149 givenname: Pierre surname: Meneton fullname: Meneton, Pierre organization: U872 Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine Paris Descartes – sequence: 152 givenname: Marjo-Riitta surname: Jarvelin fullname: Jarvelin, Marjo-Riitta organization: Department of Epidemiology and Public Health, Imperial College London, St. Mary's Campus, Norfolk Place, Department of Child and Adolescent Health, National Public Health Institute (KTL), Institute of Health Sciences and Biocenter Oulu, University of Oulu – sequence: 153 givenname: Vincent surname: Mooser fullname: Mooser, Vincent organization: Genetics Division, GlaxoSmithKline, King of Prussia – sequence: 154 givenname: Olle surname: Melander fullname: Melander, Olle organization: Department of Clinical Sciences, Lund University, Malmö University Hospital – sequence: 156 givenname: Paul surname: Elliott fullname: Elliott, Paul organization: Department of Epidemiology and Public Health, Imperial College London, St. Mary's Campus, Norfolk Place – sequence: 158 givenname: Mark surname: Caulfield fullname: Caulfield, Mark email: m.j.caulfield@qmul.ac.uk organization: Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, The Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London – sequence: 159 givenname: Patricia B surname: Munroe fullname: Munroe, Patricia B email: p.b.munroe@qmul.ac.uk organization: Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, The Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21543377$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/19430483$$D View this record in MEDLINE/PubMed https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-129032$$DView record from Swedish Publication Index https://lup.lub.lu.se/record/1424819$$DView record from Swedish Publication Index oai:portal.research.lu.se:publications/9c29cb8d-579b-41f9-9ca3-4b39d24519a7$$DView record from Swedish Publication Index http://kipublications.ki.se/Default.aspx?queryparsed=id:118831963$$DView record from Swedish Publication Index |
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| Contributor | Ferrier, I Nicol Caesar, Sian Breen, Gerome Evans, David Holmans, Peter A Morris, Andrew P Nimmo, Elaine R Jones, Richard W Jolley, Jennifer D Williamson, Richard Cant, Barbara Leung, Hin-Tak Boorman, James P Attwood, Antony P Nutland, Sarah Thompson, John R McCarthy, Mark I Onnie, Clive M Prowse, Christopher V Moskvina, Valentina Barrett, Jennifer H St Clair, David Farmer, Anne Bredin, Francesca O'Donovan, Michael C Young, Allan H Lewis, Cathryn M Koch, Kerstin Deloukas, Panos Cardon, Lon R Donnelly, Peter Clayton, David G Elkin, Amanda Samani, Nilesh J Satsangi, Jack Lees, Charles W Hall, Alistair S Marchini, Jonathan L Strachan, David P Todd, John A Winzer, Thilo Everson, Ursula Grozeva, Detelina Iles, Mark M Taylor, Niall C Burton, Paul R Duncanson, Audrey Parkes, Miles Balmforth, Anthony J Fisher, Sheila A Easton, Doug Mangino, Massimo Stevens, Suzanne Pembrey, Marcus Meech, Elizabeth Green, Elaine K Ouwehand, Willem H Gordon-Smith, Katherine Stevens, Helen E Tobin, Martin D Collier, David A Yuldasheva, Nadira Dixon, Richard J Fraser, Christi |
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| Copyright | Springer Nature America, Inc. 2009 2009 INIST-CNRS COPYRIGHT 2009 Nature Publishing Group Copyright Nature Publishing Group Jun 2009 |
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| Snippet | Christopher Newton-Cheh and colleagues report a genome-wide association study for blood pressure traits as part of the Global BPgen consortium. They report... Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood... |
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| SubjectTerms | Adaptor Proteins, Signal Transducing Agriculture Animal Genetics and Genomics Annan klinisk medicin Biological and medical sciences Biomedical and Life Sciences Biomedicine Blood pressure Blood Pressure - genetics Cancer Research Cardiac and Cardiovascular Systems Cardiology and Cardiovascular Disease Cardiovascular disease Cardiovascular diseases Cardiovascular Diseases - genetics Cardiovascular Diseases - physiopathology Chromosome Mapping Clinical Medicine Cytochrome P-450 CYP1A2 - genetics Data analysis Diastole - genetics DNA-Binding Proteins - genetics Endocrinology and Diabetes Endokrinologi och diabetes Europe Fibroblast Growth Factor 5 - genetics Fundamental and applied biological sciences. Psychology Gene Function Gene loci Genetic aspects Genetic variance Genetic Variation Genetics of eukaryotes. Biological and molecular evolution Genome-Wide Association Study Genomics Human Genetics Humans Hypertension India Intracellular Signaling Peptides and Proteins Kardiologi Kardiologi och kardiovaskulära sjukdomar Klinisk medicin Medical and Health Sciences MEDICIN Medicin och hälsovetenskap MEDICINE Meta-analysis Methylenetetrahydrofolate Reductase (NADPH2) - genetics Open Reading Frames - genetics Other Clinical Medicine Phospholipase C delta - genetics Physiological aspects Polymorphism, Single Nucleotide Proteins - genetics Risk factors Single nucleotide polymorphisms Statistics Steroid 17-alpha-Hydroxylase - genetics Studies Systole - genetics White People - genetics |
| Title | Genome-wide association study identifies eight loci associated with blood pressure |
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