Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target
Roychowdhury T, Klarin D, Levin M, Spin J, Rhee Y, Deng A, Headley C, Tsao N, Gellatly C, Zuber V, Shen F, Hornsby W, Laursen I, Verma S, Locke A, Einarsson G, Thorleifsson G, Graham S, Dikilitas O, Pattee J, Judy R, Pauls-Verges F, Nielsen J, Wolford B, Brumpton B, Dilmé J, Peypoch O, Juscafresa L, Edwards T, Li D, Banasik K, Brunak S, Jacobsen R, Garcia-Barrio M, Zhang J, Rasmussen L, Lee R, Handa A, Wanhainen A, Mani K, Lindholt J, Obel L, Strauss E, Oszkinis G, Nelson C, Saxby K, van Herwaarden J, van der Laan S, van Setten J, Camacho M, Davis F, Wasikowski R, Tsoi L, Gudjonsson J, Eliason J, Coleman D, Henke P, Ganesh S, Chen Y, Guan W, Pankow J, Pankratz N, Pedersen O, Erikstrup C, Tang W, Hveem K, Gudbjartsson D, Gretarsdottir S, Thorsteinsdottir U, Holm H, Stefansson K, Ferreira M, Baras A, Kullo I, Ritchie M, Christensen A, Iversen K, Eldrup N, Sillesen H, Ostrowski S, Bundgaard H, Ullum H, Burgess S, Gill D, Gallagher K, Sabater-Lleal M, Surakka I, Jones G, Bown M, Tsao P, Willer C, Damrauer S. Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target. Nature Genetics 2023, 55: 1831-1842. PMID: 37845353, PMCID: PMC10632148, DOI: 10.1038/s41588-023-01510-y.Peer-Reviewed Original ResearchConceptsAbdominal aortic aneurysmDevelopment of AAAAortic aneurysmNonhigh-density lipoprotein cholesterolLipid metabolismExtracellular matrix dysregulationClinical risk factorsPreclinical mouse modelsGrowth factor β signalingLipoprotein cholesterolMatrix dysregulationIndependent associationRisk factorsPCSK9 lossDiscovery cohortPolygenic risk scoresRisk lociAAA pathogenesisMouse modelRisk scoreTherapeutic targetAAA riskΒ signalingCommon diseaseMendelian randomizationGenome-wide association study of thoracic aortic aneurysm and dissection in the Million Veteran Program
Klarin D, Devineni P, Sendamarai A, Angueira A, Graham S, Shen Y, Levin M, Pirruccello J, Surakka I, Karnam P, Roychowdhury T, Li Y, Wang M, Aragam K, Paruchuri K, Zuber V, Shakt G, Tsao N, Judy R, Vy H, Verma S, Rader D, Do R, Bavaria J, Nadkarni G, Ritchie M, Burgess S, Guo D, Ellinor P, LeMaire S, Milewicz D, Willer C, Natarajan P, Tsao P, Pyarajan S, Damrauer S. Genome-wide association study of thoracic aortic aneurysm and dissection in the Million Veteran Program. Nature Genetics 2023, 55: 1106-1115. PMID: 37308786, PMCID: PMC10335930, DOI: 10.1038/s41588-023-01420-z.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesMillion Veteran ProgramProtein-altering variantsHuman genetic evidenceGenetic architectureComplex traitsGenetic evidenceDNA sequencesRisk lociMendelian formsRisk genesCell typesGenetic determinantsVeteran ProgramCurrent understandingGenesLociTraitsTAADReplicationSequenceVariants