000131473 001__ 131473
000131473 005__ 20241125101139.0
000131473 0247_ $$2doi$$a10.1016/j.ajhg.2023.08.009
000131473 0248_ $$2sideral$$a136845
000131473 037__ $$aART-2023-136845
000131473 041__ $$aeng
000131473 100__ $$avan Duijvenboden, Stefan
000131473 245__ $$aIntegration of genetic fine-mapping and multi-omics data reveals candidate effector genes for hypertension
000131473 260__ $$c2023
000131473 5060_ $$aAccess copy available to the general public$$fUnrestricted
000131473 5203_ $$aGenome-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.
000131473 536__ $$9info:eu-repo/grantAgreement/ES/AEI/PID2021-128972OA-I00$$9info:eu-repo/grantAgreement/ES/MICINN/RYC2021-031413-I
000131473 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000131473 590__ $$a8.1$$b2023
000131473 592__ $$a4.516$$b2023
000131473 591__ $$aGENETICS & HEREDITY$$b12 / 191 = 0.063$$c2023$$dQ1$$eT1
000131473 593__ $$aGenetics (clinical)$$c2023$$dQ1
000131473 593__ $$aGenetics$$c2023$$dQ1
000131473 594__ $$a14.7$$b2023
000131473 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000131473 700__ $$0(orcid)0000-0003-4130-5866$$aRamírez, Julia$$uUniversidad de Zaragoza
000131473 700__ $$aYoung, William J.
000131473 700__ $$aOlczak, Kaya J.
000131473 700__ $$aAhmed, Farah
000131473 700__ $$aAlhammadi, Mohammed J.A.Y.
000131473 700__ $$aBell, Christopher G.
000131473 700__ $$aMorris, Andrew P.
000131473 700__ $$aMunroe, Patricia B.
000131473 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000131473 773__ $$g110, 10 (2023), 1718-1734$$pAm. j. hum. genet.$$tAMERICAN JOURNAL OF HUMAN GENETICS$$x0002-9297
000131473 8564_ $$s566756$$uhttps://zaguan.unizar.es/record/131473/files/texto_completo.pdf$$yPostprint$$zinfo:eu-repo/semantics/openAccess
000131473 8564_ $$s1509131$$uhttps://zaguan.unizar.es/record/131473/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint$$zinfo:eu-repo/semantics/openAccess
000131473 909CO $$ooai:zaguan.unizar.es:131473$$particulos$$pdriver
000131473 951__ $$a2024-11-22-12:02:10
000131473 980__ $$aARTICLE