2024
Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis
Ghouse J, Sveinbjörnsson G, Vujkovic M, Seidelin A, Gellert-Kristensen H, Ahlberg G, Tragante V, Rand S, Brancale J, Vilarinho S, Lundegaard P, Sørensen E, Erikstrup C, Bruun M, Jensen B, Brunak S, Banasik K, Ullum H, Verweij N, Lotta L, Baras A, Mirshahi T, Carey D, Kaplan D, Lynch J, Morgan T, Schwantes-An T, Dochtermann D, Pyarajan S, Tsao P, Laisk T, Mägi R, Kozlitina J, Tybjærg-Hansen A, Jones D, Knowlton K, Nadauld L, Ferkingstad E, Björnsson E, Ulfarsson M, Sturluson Á, Sulem P, Pedersen O, Ostrowski S, Gudbjartsson D, Stefansson K, Olesen M, Chang K, Holm H, Bundgaard H, Stender S. Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis. Nature Genetics 2024, 56: 827-837. PMID: 38632349, PMCID: PMC11096111, DOI: 10.1038/s41588-024-01720-y.Peer-Reviewed Original ResearchMeSH KeywordsAlanine TransaminaseCarcinoma, HepatocellularCase-Control StudiesCohort StudiesFemaleGamma-GlutamyltransferaseGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyHumansLipaseLiver CirrhosisLiver NeoplasmsMaleMembrane ProteinsMultifactorial InheritancePolymorphism, Single NucleotideRisk FactorsConceptsMulti-ancestry genome-wide association studyPolygenic risk scoresRare variant analysisVariant analysisGenome-wide association studiesRare coding variantsHepatocellular carcinomaLow alanine aminotransferaseRisk associationAlcohol intakePrioritized genesGenetic architectureNear genesAlanine aminotransferaseRisk scoreHepatic lipid metabolismAssociation studiesLiver cirrhosisGenetic underpinningsPNPLA3 p.Cirrhosis to hepatocellular carcinomaRisk of cirrhosisLiver function testsLipid metabolismGenes
2021
GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension
Drzewiecki K, Choi J, Brancale J, Leney-Greene MA, Sari S, Dalgiç B, Aksu A, Şahin G, Ozen A, Baris S, Karakoc-Aydiner E, Jain D, Kleiner D, Schmalz M, Radhakrishnan K, Zhang J, Hoebe K, Su HC, Pereira JP, Lenardo MJ, Lifton RP, Vilarinho S. GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension. Journal Of Experimental Medicine 2021, 218: e20201745. PMID: 33956074, PMCID: PMC8105721, DOI: 10.1084/jem.20201745.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsPortal hypertensionEndothelial cell homeostasisHepatic endothelial cellsEndothelial cellsLiver diseaseUnexplained portal hypertensionGlobal health problemSinusoidal endothelial cellsCell homeostasisSingle-cell RNA-sequencing analysisHypertensionMouse modelHealth problemsMice resultsGimap5RNA sequence analysisMajor contributorCritical regulatorDiseaseCellsDamaging mutationsHomeostasisDecompensationMorbidity
2019
Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood
Khera AV, Chaffin M, Wade KH, Zahid S, Brancale J, Xia R, Distefano M, Senol-Cosar O, Haas ME, Bick A, Aragam KG, Lander ES, Smith GD, Mason-Suares H, Fornage M, Lebo M, Timpson NJ, Kaplan LM, Kathiresan S. Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood. Cell 2019, 177: 587-596.e9. PMID: 31002795, PMCID: PMC6661115, DOI: 10.1016/j.cell.2019.03.028.Peer-Reviewed Original ResearchConceptsSevere obesityLongitudinal birth cohortYears of ageUnhealthy lifestyle choicesMiddle-aged adultsGlobal health threatObesity trajectoriesClinical preventionBirth cohortObesityHealth threatPolygenic predictorsInherited susceptibilityLifestyle choicesEarly childhoodCommon variantsBirthAgeCommon DNA variantsPredictorsMinimal differencesSusceptibilityMechanistic assessmentDecileBirthweight
2017
Effect of Sofosbuvir-Based Hepatitis C Virus Therapy on Kidney Function in Patients with CKD
Sise ME, Backman E, Ortiz GA, Hundemer GL, Ufere NN, Chute DF, Brancale J, Xu D, Wisocky J, Lin MV, Kim AY, Thadhani R, Chung RT. Effect of Sofosbuvir-Based Hepatitis C Virus Therapy on Kidney Function in Patients with CKD. Clinical Journal Of The American Society Of Nephrology 2017, 12: 1615-1623. PMID: 28882857, PMCID: PMC5628711, DOI: 10.2215/cjn.02510317.Peer-Reviewed Original ResearchConceptsSustained virologic responseAdverse eventsVirologic responseAntiviral therapyOverall sustained virologic responsePrior solid organ transplantHepatitis C virus (HCV) therapyEffect of sofosbuvirEfficacy of sofosbuvirHepatitis C cureRetrospective observational cohortC virus infectionSerious adverse eventsSolid organ transplantsC virus therapyCohort of patientsLarge health care systemPost-treatment followHepatitis C virusHealth care systemBaseline eGFRTreatment discontinuationObservational cohortKidney functionRegression models