2023
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 randomization
2021
Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm
Roychowdhury T, Lu H, Hornsby WE, Crone B, Wang GT, Guo DC, Sendamarai AK, Devineni P, Lin M, Zhou W, Graham SE, Wolford BN, Surakka I, Wang Z, Chang L, Zhang J, Mathis M, Brummett CM, Melendez TL, Shea MJ, Kim KM, Deeb GM, Patel HJ, Eliason J, Eagle KA, Yang B, Ganesh SK, Brumpton B, Åsvold BO, Skogholt AH, Hveem K, Program V, Pyarajan S, Klarin D, Tsao PS, Damrauer SM, Leal SM, Milewicz DM, Chen YE, Garcia-Barrio MT, Willer CJ. Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm. American Journal Of Human Genetics 2021, 108: 1578-1589. PMID: 34265237, PMCID: PMC8456156, DOI: 10.1016/j.ajhg.2021.06.016.Peer-Reviewed Original ResearchMeSH KeywordsAortaAortic Aneurysm, ThoracicBcl-2-Associated X ProteinCase-Control StudiesCaspase 3Diabetes Mellitus, Type 2Endothelial CellsGene Expression RegulationGenome, HumanGenome-Wide Association StudyHumansIntronsMichiganMuscle, Smooth, VascularMutationProto-Oncogene Proteins c-bcl-2Quantitative Trait LociTranscription Factor 7-Like 2 ProteinConceptsGenome-wide significant associationDifferent causal variantsGenome-wide scanCommon variantsVascular smooth muscle cell apoptosisSmooth muscle cell apoptosisMuscle cell apoptosisRegulatory variantsGenomics initiativesSingle geneThird intronCausal variantsMichigan Genomics InitiativeHeritable diseaseType 2 diabetesCell apoptosisGenetic associationAdditional independent cohortsTCF7L2Aortic aneurysmLociHigh expressionTAAGenetic risk factorsFunctional relationship