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
2020
GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer
Zhou W, Brumpton B, Kabil O, Gudmundsson J, Thorleifsson G, Weinstock J, Zawistowski M, Nielsen JB, Chaker L, Medici M, Teumer A, Naitza S, Sanna S, Schultheiss UT, Cappola A, Karjalainen J, Kurki M, Oneka M, Taylor P, Fritsche LG, Graham SE, Wolford BN, Overton W, Rasheed H, Haug EB, Gabrielsen ME, Skogholt AH, Surakka I, Davey Smith G, Pandit A, Roychowdhury T, Hornsby WE, Jonasson JG, Senter L, Liyanarachchi S, Ringel MD, Xu L, Kiemeney LA, He H, Netea-Maier RT, Mayordomo JI, Plantinga TS, Hrafnkelsson J, Hjartarson H, Sturgis EM, Palotie A, Daly M, Citterio CE, Arvan P, Brummett CM, Boehnke M, de la Chapelle A, Stefansson K, Hveem K, Willer CJ, Åsvold BO. GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer. Nature Communications 2020, 11: 3981. PMID: 32769997, PMCID: PMC7414135, DOI: 10.1038/s41467-020-17718-z.Peer-Reviewed Original ResearchConceptsPleiotropic effectsGenome-wide significant lociPhenome-wide association analysisSignificant lociGenetic markersAssociation analysisUK BiobankNormal developmentFunctional experimentsIndex variantsGenetic contributionGWASTwo-sample Mendelian randomizationPolygenic scoresVariantsMendelian randomizationLociG67Independent studiesThyroid cancerMetabolismBiobankHormoneThyroglobulin secretion