Large-Scale Multi-Omics Studies Provide New Insights into Blood Pressure Regulation

Autor:	Kamali, Zoha, Keaton, Jacob M., Javanmard, Shaghayegh Haghjooy, Edwards, Todd L., Snieder, Harold, Vaez, Ahmad, Boomsma, Dorret, de Geus, Eco J.C., Hottenga, Jouke Jan, Willemsen, Gonneke, van Dongen, Jenny, Pool, René, Jansen, Rick, Penninx, Brenda WJH
Přispěvatelé:	APH - Methodology, APH - Mental Health, Amsterdam Reproduction & Development, Biological Psychology, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Life Course Epidemiology (LCE)
Jazyk:	angličtina
Rok vydání:	2022
Předmět:	Epigenomics Blood Pressure/genetics epigenome Blood Pressure Catalysis Epigenesis Genetic Inorganic Chemistry SDG 3 - Good Health and Well-being Genetic Humans Physical and Theoretical Chemistry Molecular Biology genome Spectroscopy blood pressure gene expression functional enrichment Organic Chemistry General Medicine Genomics Epigenomics/methods Computer Science Applications Genomics/methods Transcriptome Epigenesis Genome-Wide Association Study
Zdroj:	International Journal of Molecular Sciences, 23(14):7557. Multidisciplinary Digital Publishing Institute (MDPI) International Journal of Molecular Sciences; Volume 23; Issue 14; Pages: 7557 International Journal of Molecular Sciences, 23(14):7557. MDPI AG Kamali, Z, Keaton, J M, Javanmard, S H, Edwards, T L, Snieder, H, Vaez, A, International Consortium of Blood Pressure, Million Veteran Program, eQTLGen Consortium, BIOS Consortium, Boomsma, D, de Geus, E J C, Hottenga, J J, Willemsen, G, van Dongen, J, Pool, R, Jansen, R & Penninx, B WJH 2022, ' Large-Scale Multi-Omics Studies Provide New Insights into Blood Pressure Regulation ', International Journal of Molecular Sciences, vol. 23, no. 14, 7557 . https://doi.org/10.3390/ijms23147557
ISSN:	1422-0067 1661-6596
DOI:	10.3390/ijms23147557
Popis:	Recent genome-wide association studies uncovered part of blood pressure’s heritability. However, there is still a vast gap between genetics and biology that needs to be bridged. Here, we followed up blood pressure genome-wide summary statistics of over 750,000 individuals, leveraging comprehensive epigenomic and transcriptomic data from blood with a follow-up in cardiovascular tissues to prioritise likely causal genes and underlying blood pressure mechanisms. We first prioritised genes based on coding consequences, multilayer molecular associations, blood pressure-associated expression levels, and coregulation evidence. Next, we followed up the prioritised genes in multilayer studies of genomics, epigenomics, and transcriptomics, functional enrichment, and their potential suitability as drug targets. Our analyses yielded 1880 likely causal genes for blood pressure, tens of which are targets of the available licensed drugs. We identified 34 novel genes for blood pressure, supported by more than one source of biological evidence. Twenty-eight (82%) of these new genes were successfully replicated by transcriptome-wide association analyses in a large independent cohort (n = ~220,000). We also found a substantial mediating role for epigenetic regulation of the prioritised genes. Our results provide new insights into genetic regulation of blood pressure in terms of likely causal genes and involved biological pathways offering opportunities for future translation into clinical practice.
Databáze:	OpenAIRE
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