131473 20241125101139.0 doi 10.1016/j.ajhg.2023.08.009 sideral 136845 ART-2023-136845 eng van Duijvenboden, Stefan Integration of genetic fine-mapping and multi-omics data reveals candidate effector genes for hypertension 2023 Access copy available to the general public Unrestricted Genome-wide association studies of blood pressure (BP) have identified >1,000 loci, but the effector genes and biological pathways at these loci are mostly unknown. Using published association summary statistics, we conducted annotation-informed fine-mapping incorporating tissue-specific chromatin segmentation and colocalization to identify causal variants and candidate effector genes for systolic BP, diastolic BP, and pulse pressure. We observed 532 distinct signals associated with ≥2 BP traits and 84 with all three. For >20% of signals, a single variant accounted for >75% posterior probability, 65 were missense variants in known (SLC39A8, ADRB2, and DBH) and previously unreported BP candidate genes (NRIP1 and MMP14). In disease-relevant tissues, we colocalized >80 and >400 distinct signals for each BP trait with cis-eQTLs and regulatory regions from promoter capture Hi-C, respectively. Integrating mouse, human disorder, gene expression and tissue abundance data, and literature review, we provide consolidated evidence for 436 BP candidate genes for future functional validation and discover several potential drug targets. info:eu-repo/grantAgreement/ES/AEI/PID2021-128972OA-I00 info:eu-repo/grantAgreement/ES/MICINN/RYC2021-031413-I info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 8.1 2023 GENETICS & HEREDITY 12 / 191 = 0.063 2023 Q1 T1 4.516 2023 Genetics (clinical) 2023 Q1 Genetics 2023 Q1 14.7 2023 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Ramírez, Julia Universidad de Zaragoza (orcid)0000-0003-4130-5866 Young, William J. Olczak, Kaya J. Ahmed, Farah Alhammadi, Mohammed J.A.Y. Bell, Christopher G. Morris, Andrew P. Munroe, Patricia B. 5008 800 Universidad de Zaragoza Dpto. Ingeniería Electrón.Com. Área Teoría Señal y Comunicac. 110, 10 (2023), 1718-1734 Am. j. hum. genet. AMERICAN JOURNAL OF HUMAN GENETICS 0002-9297 566756 http://zaguan.unizar.es/record/131473/files/texto_completo.pdf Postprint info:eu-repo/date/embargoEnd/2024-03-07 1509131 http://zaguan.unizar.es/record/131473/files/texto_completo.jpg?subformat=icon icon Postprint info:eu-repo/date/embargoEnd/2024-03-07 oai:zaguan.unizar.es:131473 articulos driver 2024-11-22-12:02:10 ARTICLE