Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
(2020) In Nature Genetics 52(12). p.1314-1332- Abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin... (More)
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. (Less)
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- author
- author collaboration
- organization
-
- Cardiovascular Research - Hypertension (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- EpiHealth: Epidemiology for Health
- Diabetes - Cardiovascular Disease (research group)
- Genetic and Molecular Epidemiology (research group)
- Diabetic Complications (research group)
- Translational Muscle Research (research group)
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Genetics
- volume
- 52
- issue
- 12
- pages
- 19 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85096546970
- pmid:33230300
- ISSN
- 1546-1718
- DOI
- 10.1038/s41588-020-00713-x
- language
- English
- LU publication?
- yes
- additional info
- Export Date: 9 December 2020
- id
- ab3cf679-db71-435f-9907-67f295345e04
- date added to LUP
- 2020-12-09 11:06:18
- date last changed
- 2024-05-02 21:28:43
@article{ab3cf679-db71-435f-9907-67f295345e04, abstract = {{Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.}}, author = {{Surendran, Praveen and Fava, Cristiano and Melander, Olle and Orho-Melander, Marju and Poveda, Alaitz and V. Varga, Tibor and Renström, Frida and Franks, Paul and Tuomi, Tiinamaija and Almgren, Peter and Groop, Leif and Howson, Joanna M. M.}}, issn = {{1546-1718}}, language = {{eng}}, number = {{12}}, pages = {{1314--1332}}, publisher = {{Nature Publishing Group}}, series = {{Nature Genetics}}, title = {{Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals}}, url = {{http://dx.doi.org/10.1038/s41588-020-00713-x}}, doi = {{10.1038/s41588-020-00713-x}}, volume = {{52}}, year = {{2020}}, }