2025
Examining socioeconomic differences in sepsis risk and mediation by modifiable factors: a Mendelian randomization study
Stensrud V, Rogne T, Flatby H, Mohus R, Gustad L, Nilsen T. Examining socioeconomic differences in sepsis risk and mediation by modifiable factors: a Mendelian randomization study. BMC Infectious Diseases 2025, 25: 739. PMID: 40410669, PMCID: PMC12103053, DOI: 10.1186/s12879-025-11130-y.Peer-Reviewed Original ResearchMeSH KeywordsEducational StatusFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMendelian Randomization AnalysisRisk FactorsSepsisSocioeconomic FactorsConceptsSummary-level dataSocioeconomic differencesGenome-wide association studiesGenetic instrumentsEducational attainmentMendelian randomizationMR analysisStandard deviation increaseBias due to population stratificationOdds ratioPreventive factorsMR-Egger regressionExamined socioeconomic differencesMultivariable MR analysisEffect of smoking initiationAssociation studiesMendelian randomization studiesEffects of educational attainmentDeviation increaseYears of educationBody mass indexBackgroundEducational attainmentDynastic effectsMedian OREgger regressionThe inflammatory and genetic mechanisms underlying the cumulative effect of co-occurring pain conditions on depression
Jiang R, Geha P, Rosenblatt M, Wang Y, Fu Z, Foster M, Dai W, Calhoun V, Sui J, Spann M, Scheinost D. The inflammatory and genetic mechanisms underlying the cumulative effect of co-occurring pain conditions on depression. Science Advances 2025, 11: eadt1083. PMID: 40173244, PMCID: PMC11964001, DOI: 10.1126/sciadv.adt1083.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiomarkersC-Reactive ProteinChronic PainComorbidityDepressionFemaleGenetic Predisposition to DiseaseHumansInflammationMaleMendelian Randomization AnalysisMiddle AgedPainRisk FactorsConceptsDepression riskChronic pain conditionsPain conditionsPrevalence of comorbid depressionPain scoresUK Biobank participantsPain-free individualsComposite pain scoresHigh-risk individualsPain screeningMendelian randomizationBiobank participantsPain sitesDepression incidenceComorbid depressionIncreased riskBody sitesDepressionC-reactive proteinPainCausal inferenceFollow-upScoresRiskInflammatory markersBrain-wide pleiotropy investigation of alcohol drinking and tobacco smoking behaviors
Deiana G, He J, Cabrera-Mendoza B, Ciccocioppo R, Napolioni V, Polimanti R. Brain-wide pleiotropy investigation of alcohol drinking and tobacco smoking behaviors. Translational Psychiatry 2025, 15: 61. PMID: 39979292, PMCID: PMC11842717, DOI: 10.1038/s41398-025-03288-5.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAlcohol DrinkingBrainFemaleGenetic PleiotropyGenome-Wide Association StudyHumansMagnetic Resonance ImagingMaleMendelian Randomization AnalysisMiddle AgedPhenotypeTobacco SmokingUnited KingdomWhite MatterConceptsImaging-derived phenotypesBrain imaging-derived phenotypesAlcohol drinkingBrain structuresProcessing of social cuesCorrelates of smoking behaviorRelationship of brain structureSequencing Consortium of AlcoholGlobal genetic correlationsSmoking behaviorSuperior longitudinal fasciculusAssociated with smoking initiationTobacco smokeTobacco smoking behaviorLatent causal variable approachesNicotine useBrain regionsPremotor cortexSocial cuesWhite matter hyperintensitiesLongitudinal fasciculusChemosensory processingCortical thicknessMendelian randomizationPleiotropic mechanismsBidirectional relationship between epigenetic age and stroke, dementia, and late-life depression
Rivier C, Szejko N, Renedo D, Clocchiatti-Tuozzo S, Huo S, de Havenon A, Zhao H, Gill T, Sheth K, Falcone G. Bidirectional relationship between epigenetic age and stroke, dementia, and late-life depression. Nature Communications 2025, 16: 1261. PMID: 39893209, PMCID: PMC11787333, DOI: 10.1038/s41467-024-54721-0.Peer-Reviewed Original ResearchThis study shows a bidirectional link between accelerated epigenetic aging and brain health events like stroke, dementia, and depression, supporting new prevention strategies for aging-related conditions.Sensitivity to Environmental Stress and Adversity and Lung Cancer
Chen Y, Lan Q, Yu J, Godbole D, Byun J, Amos C, Zhang H. Sensitivity to Environmental Stress and Adversity and Lung Cancer. JAMA Network Open 2025, 8: e2457079. PMID: 39878978, PMCID: PMC11780474, DOI: 10.1001/jamanetworkopen.2024.57079.Peer-Reviewed Original ResearchMeSH KeywordsAgedFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLung NeoplasmsMaleMendelian Randomization AnalysisMiddle AgedRisk FactorsStress, PsychologicalConceptsLung cancer riskAssociated with lung cancer riskInternational Lung Cancer ConsortiumIndividuals of European ancestryCancer riskGenetic association studiesMendelian randomizationCross-ancestryCancer ConsortiumAssociation studiesInfluence lung cancer riskIncreased risk of lung cancerEuropean ancestryRisk of lung cancerGenome-wide meta-analysisIncreased riskGenome-wide association studiesLung cancer casesIndividuals of African ancestryIndividuals of East Asian ancestryEast Asian ancestryUK BiobankPsychosocial factorsMain OutcomesCancer cases
2024
Autoimmune Diseases and Risk of Non‐Hodgkin Lymphoma: A Mendelian Randomisation Study
Shi X, Wallach J, Ma X, Rogne T. Autoimmune Diseases and Risk of Non‐Hodgkin Lymphoma: A Mendelian Randomisation Study. Cancer Medicine 2024, 13: e70327. PMID: 39506244, PMCID: PMC11540836, DOI: 10.1002/cam4.70327.Peer-Reviewed Original ResearchConceptsRisk of non-Hodgkin lymphomaNon-Hodgkin's lymphomaAutoimmune diseasesMendelian randomisationType 1 diabetesAssociated with risk of non-Hodgkin lymphomaWeak instrument biasNon-Hodgkin lymphoma subtypesTwo-sample MRNon-Hodgkin lymphoma riskRisk factorsSusceptibility to type 1 diabetesMendelian randomisation studiesCohorts of European ancestryAssociated with riskNo significant associationPotential pleiotropyPotential risk factorsUK BiobankFinnGen studyNon-HodgkinHaematological malignanciesRandomised studyEuropean ancestrySignificant associationAssociation between cannabis use and brain structure and function: an observational and Mendelian randomisation study
Ishrat S, Levey D, Gelernter J, Ebmeier K, Topiwala A. Association between cannabis use and brain structure and function: an observational and Mendelian randomisation study. BMJ Mental Health 2024, 27: e301065. PMID: 39477366, PMCID: PMC11529520, DOI: 10.1136/bmjment-2024-301065.Peer-Reviewed Original ResearchMeSH KeywordsAgedBrainFemaleHumansMagnetic Resonance ImagingMaleMarijuana UseMendelian Randomization AnalysisMiddle AgedUnited KingdomWhite MatterConceptsCannabis useBrain structuresFunctional connectivityHistory of cannabis useResting-state functional connectivityMeasures of brain structureLifetime cannabis useCentral executive networkLifetime cannabis usersWhite matter integrityGenu of the corpus callosumMendelian randomisation analysisAssociated with multiple measuresPoorer white matter integrityInvestigate potential causal relationshipsCannabis usersExecutive networkBrain regionsImaging-derived phenotypesBrain healthCannabisRandomisation analysesTwo-sample Mendelian randomisation analysisFractional anisotropyYoung adulthoodThe brain structure, inflammatory, and genetic mechanisms mediate the association between physical frailty and depression
Jiang R, Noble S, Rosenblatt M, Dai W, Ye J, Liu S, Qi S, Calhoun V, Sui J, Scheinost D. The brain structure, inflammatory, and genetic mechanisms mediate the association between physical frailty and depression. Nature Communications 2024, 15: 4411. PMID: 38782943, PMCID: PMC11116547, DOI: 10.1038/s41467-024-48827-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiomarkersBrainC-Reactive ProteinCross-Sectional StudiesDepressionFemaleFrailtyHumansInflammationMaleMendelian Randomization AnalysisMiddle AgedNeutrophilsProspective StudiesRisk FactorsUnited KingdomConceptsIncident depressionPre-frailPhysical frailtyFrail individualsPopulation attributable fraction analysisRisk factors of depressionMendelian randomization analysisFactors of depressionPotential causal effectModifiable risk factorsNon-frail individualsCross-sectional studyEffect of frailtyHigher disease burdenUK BiobankRandomization analysisBrain volumeDepression casesDisease burdenFrailtyRegional brain volumesIncreased riskDepressionHigh riskFollow-upA phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals
Jennings M, Martínez-Magaña J, Courchesne-Krak N, Cupertino R, Vilar-Ribó L, Bianchi S, Hatoum A, Atkinson E, Giusti-Rodriguez P, Montalvo-Ortiz J, Gelernter J, Artigas M, 23andMe I, Aslibekyan S, Auton A, Babalola E, Bell R, Bielenberg J, Bryc K, Bullis E, Coker D, Partida G, Dhamija D, Das S, Elson S, Eriksson N, Filshtein T, Fitch A, Fletez-Brant K, Fontanillas P, Freyman W, Granka J, Heilbron K, Hernandez A, Hicks B, Hinds D, Jewett E, Jiang Y, Kukar K, Kwong A, Lin K, Llamas B, Lowe M, McCreight J, McIntyre M, Micheletti S, Moreno M, Nandakumar P, Nguyen D, Noblin E, O'Connell J, Petrakovitz A, Poznik G, Reynoso A, Schumacher M, Shastri A, Shelton J, Shi J, Shringarpure S, Su Q, Tat S, Tchakouté C, Tran V, Tung J, Wang X, Wang W, Weldon C, Wilton P, Wong C, Elson S, Edenberg H, Fontanillas P, Palmer A, Sanchez-Roige S. A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals. EBioMedicine 2024, 103: 105086. PMID: 38580523, PMCID: PMC11121167, DOI: 10.1016/j.ebiom.2024.105086.Peer-Reviewed Original ResearchConceptsMultiple domains of healthDomains of healthEffects of alcohol consumptionAlcohol consumptionHealth outcomesPhenome-wide association studyAlcohol-related behaviorsCardio-metabolic healthPotential causal effectMendelian randomisation studiesGenome-wide association studiesPhenome-wide associationMR analysisPheWAS associationsMultiple domainsHypothesis-free approachPreventive medicineDiverse cohortPheWASAssociation studiesHealthReproductive healthAlcohol behaviorConsequences of drinkingEuropean cohortMediating Factors in the Association of Maternal Educational Level With Pregnancy Outcomes
Rogne T, Gill D, Liew Z, Shi X, Stensrud V, Nilsen T, Burgess S. Mediating Factors in the Association of Maternal Educational Level With Pregnancy Outcomes. JAMA Network Open 2024, 7: e2351166. PMID: 38206626, PMCID: PMC10784860, DOI: 10.1001/jamanetworkopen.2023.51166.Peer-Reviewed Original ResearchMeSH KeywordsBirth WeightCholesterolCohort StudiesDiabetes Mellitus, Type 2Educational StatusFemaleGenome-Wide Association StudyHumansHyperemesis GravidarumInfant, NewbornLipoproteins, HDLMediation AnalysisMendelian Randomization AnalysisPre-EclampsiaPregnancyPregnancy OutcomePregnancy, EctopicPremature BirthConceptsCardiometabolic risk factorsBody mass indexOffspring birth weightEducational attainmentMendelian randomizationHigh-density lipoprotein cholesterol levelsSystolic blood pressureInverse variance-weighted methodModifiable cardiometabolic risk factorsPregnancy outcomesCohort studyLipoprotein cholesterol levelsMR-Egger regressionMass indexUnivariable MR analysisEffects of educational attainmentAssociated with increased risk of adverse pregnancy outcomesPublic health interventionsMaternal education levelLower educational attainmentRisk factorsRisk of adverse pregnancy outcomesGenome-wide association studiesAssociated with increased riskBirth weight
2023
Elucidating the role of blood metabolites on pancreatic cancer risk using two‐sample Mendelian randomization analysis
Zhong H, Liu S, Zhu J, Xu T, Yu H, Wu L. Elucidating the role of blood metabolites on pancreatic cancer risk using two‐sample Mendelian randomization analysis. International Journal Of Cancer 2023, 154: 852-862. PMID: 37860916, PMCID: PMC10843029, DOI: 10.1002/ijc.34771.Peer-Reviewed Original ResearchMeSH KeywordsCanadaCarcinoma, Pancreatic DuctalGenome-Wide Association StudyHumansLongitudinal StudiesMendelian Randomization AnalysisPancreatic NeoplasmsConceptsPancreatic ductal adenocarcinomaPDAC riskBlood metabolitesGenetic instrumentsTwo-sample Mendelian randomization studyPancreatic Cancer Case-Control ConsortiumEPIC-Norfolk cohortPancreatic cancer riskEuropean ancestryPancreatic Cancer Cohort ConsortiumPotential side effectsCanadian Longitudinal StudyAssociations of metabolitesMendelian randomization studyTwo-sample Mendelian randomization (MR) analysisGenome-wide association studiesMendelian randomization analysisFatal malignancyDuctal adenocarcinomaCancer riskPDAC casesSide effectsAging CohortMetabolite biomarkersRandomization studyProspective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer
Nimptsch K, Aleksandrova K, Pham T, Papadimitriou N, Janke J, Christakoudi S, Heath A, Olsen A, Tjønneland A, Schulze M, Katzke V, Kaaks R, van Guelpen B, Harbs J, Palli D, Macciotta A, Pasanisi F, Yohar S, Guevara M, Amiano P, Grioni S, Jakszyn P, Figueiredo J, Samadder N, Li C, Moreno V, Potter J, Schoen R, Um C, Weiderpass E, Jenab M, Gunter M, Pischon T. Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer. BMC Medicine 2023, 21: 391. PMID: 37833736, PMCID: PMC10576353, DOI: 10.1186/s12916-023-03104-1.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesColorectal NeoplasmsFemaleGenome-Wide Association StudyHumansMaleMendelian Randomization AnalysisPolymorphism, Single NucleotideProspective StudiesRisk FactorsConceptsColorectal cancer riskColorectal cancer casesMendelian randomizationColorectal cancerEpidemiology of Colorectal Cancer ConsortiumAssociated with colorectal cancer riskTwo-sample Mendelian randomization studyColon Cancer Family RegistryPublished genome-wide association studiesColorectal Cancer ConsortiumCancer Family RegistryConditional logistic regression modelsMendelian randomization analysisMendelian randomization studiesCancer and NutritionEuropean Prospective InvestigationNested case-control studyGenome-wide association studiesLogistic regression modelsCase-control studyDevelopment of colorectal cancerFamily RegistryStatistically significant associationCancer ConsortiumCancer riskGenome-wide association studies and cross-population meta-analyses investigating short and long sleep duration
Austin-Zimmerman I, Levey D, Giannakopoulou O, Deak J, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Concato J, Buysse D, Gaziano J, Gottlieb D, Polimanti R, Stein M, Bramon E, Gelernter J. Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration. Nature Communications 2023, 14: 6059. PMID: 37770476, PMCID: PMC10539313, DOI: 10.1038/s41467-023-41249-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultGenome-Wide Association StudyHumansMendelian Randomization AnalysisPhenotypePolymorphism, Single NucleotideSleepSleep DurationConceptsAssociation studiesGenome-wide association studiesGenetic correlationsWide association studyLinkage disequilibrium scorePositive genetic correlationSleep traitsIndependent lociMillion Veteran ProgramTraitsAncestryUK BiobankVeteran ProgramMendelian randomisationLociHeritabilitySNPsPhenotypeEast AsiansSimilar patternCardiometabolic phenotypesAge at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women
Tschiderer L, Peters S, van der Schouw Y, van Westing A, Tong T, Willeit P, Seekircher L, Moreno‐Iribas C, Huerta J, Crous‐Bou M, Söderholm M, Schulze M, Johansson C, Själander S, Heath A, Macciotta A, Dahm C, Ibsen D, Pala V, Mellemkjær L, Burgess S, Wood A, Kaaks R, Katzke V, Amiano P, Rodriguez‐Barranco M, Engström G, Weiderpass E, Tjønneland A, Halkjær J, Panico S, Danesh J, Butterworth A, Onland‐Moret N. Age at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women. Journal Of The American Heart Association 2023, 12: e030280. PMID: 37681566, PMCID: PMC10547274, DOI: 10.1161/jaha.123.030280.Peer-Reviewed Original ResearchMeSH KeywordsCerebral HemorrhageFemaleHemorrhagic StrokeHumansIschemic StrokeMendelian Randomization AnalysisMenopauseMiddle AgedObservational Studies as TopicPostmenopauseProspective StudiesStrokeConceptsMendelian randomization analysisRisk of strokeStatistically significant associationRandomization analysisSignificant associationHistory of strokeEPIC-CVDPooled mean ageHigh risk of strokeUK BiobankYears younger ageBaseline ageHazard ratioStroke subtypesObservational studyPooled hazard ratioHemorrhagic strokeEarly menopauseYounger ageMean ageHigh riskMedian follow-upStrokeRegression analysisWomenGenetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization.
King S, Veliginti S, Brouwers M, Ren Z, Zheng W, Setiawan V, Wilkens L, Shu X, Arslan A, Beane Freeman L, Bracci P, Canzian F, Du M, Gallinger S, Giles G, Goodman P, Haiman C, Kogevinas M, Kooperberg C, LeMarchand L, Neale R, Visvanathan K, White E, Albanes D, Andreotti G, Babic A, Berndt S, Brais L, Brennan P, Buring J, Rabe K, Bamlet W, Chanock S, Fuchs C, Gaziano J, Giovannucci E, Hackert T, Hassan M, Katzke V, Kurtz R, Lee I, Malats N, Murphy N, Oberg A, Orlow I, Porta M, Real F, Rothman N, Sesso H, Silverman D, Thompson I, Wactawski-Wende J, Wang X, Wentzensen N, Yu H, Zeleniuch-Jacquotte A, Yu K, Wolpin B, Duell E, Li D, Hung R, Perdomo S, McCullough M, Freedman N, Patel A, Peters U, Riboli E, Sund M, Tjønneland A, Zhong J, Van Den Eeden S, Kraft P, Risch H, Amundadottir L, Klein A, Stolzenberg-Solomon R, Antwi S. Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization. Cancer Epidemiology Biomarkers & Prevention 2023, 32: 1265-1269. PMID: 37351909, PMCID: PMC10529823, DOI: 10.1158/1055-9965.epi-23-0453.Peer-Reviewed Original ResearchMeSH KeywordsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMendelian Randomization AnalysisNon-alcoholic Fatty Liver DiseaseObesityPancreatic NeoplasmsPolymorphism, Single NucleotideConceptsNonalcoholic fatty liver diseasePancreatic cancer riskFatty liver diseasePancreatic cancerCancer riskLiver diseaseGenetic predispositionMendelian randomizationPancreatic Cancer Case-Control ConsortiumConfidence intervalsPancreatic Cancer Cohort ConsortiumPC risk factorsMR methodsRisk factorsGenome-wide association studiesGenetic susceptibilityLogistic regressionCancerMetabolic perturbationsMetabolic conditionsRiskDiseaseGenetic variantsAssociationPredispositionMendelian randomization study of birthweight, gestational age, and risk of childhood acute lymphoblastic leukemia
Rogne T, DeWan A, Metayer C, Wiemels J, Ma X. Mendelian randomization study of birthweight, gestational age, and risk of childhood acute lymphoblastic leukemia. American Journal Of Obstetrics & Gynecology MFM 2023, 5: 101058. PMID: 37330008, DOI: 10.1016/j.ajogmf.2023.101058.Peer-Reviewed Original ResearchMeSH KeywordsBirth WeightGestational AgeHumansMendelian Randomization AnalysisPrecursor Cell Lymphoblastic Leukemia-LymphomaRisk FactorsPros and cons of Mendelian randomization
Zhang H. Pros and cons of Mendelian randomization. Fertility And Sterility 2023, 119: 913-916. PMID: 36990264, PMCID: PMC10234673, DOI: 10.1016/j.fertnstert.2023.03.029.Peer-Reviewed Original ResearchCirculating levels of micronutrients and risk of infections: a Mendelian randomization study
Flatby H, Ravi A, Damås J, Solligård E, Rogne T. Circulating levels of micronutrients and risk of infections: a Mendelian randomization study. BMC Medicine 2023, 21: 84. PMID: 36882828, PMCID: PMC9993583, DOI: 10.1186/s12916-023-02780-3.Peer-Reviewed Original ResearchConceptsRisk of infectionGastrointestinal infectionsBlood levelsMendelian randomizationMendelian randomization studyOdds ratioObservational studyImmune responseIndependent cohortRandomization studySignificant associationInfectionClear associationMR analysisLevels of micronutrientsStatistical significanceConclusionsOur resultsPrevious observational studiesStandard deviation increaseUK BiobankRiskLevels of copperEuropean ancestryAvailable summary statisticsAssociationDyslipidemia and Risk of Preeclampsia: A Multiancestry Mendelian Randomization Study
Hosier H, Lipkind H, Rasheed H, DeWan A, Rogne T. Dyslipidemia and Risk of Preeclampsia: A Multiancestry Mendelian Randomization Study. Hypertension 2023, 80: 1067-1076. PMID: 36883459, DOI: 10.1161/hypertensionaha.122.20426.Peer-Reviewed Original ResearchConceptsRisk of preeclampsiaProtective effectCholesteryl Ester Transfer Protein InhibitionLack of effectMendelian randomization studyMendelian randomization analysisMaternal morbidityElevated HDLLeading causeLipid levelsObservational studyPreeclampsiaLipid measurementsReduced riskAncestry groupsPharmacological targetsRandomization studyHDLLDLRandomization analysisSingle nucleotide polymorphismsNew targetsDyslipidemiaRiskProtein inhibitionSex‐Specific Reproductive Factors Augment Cardiovascular Disease Risk in Women: A Mendelian Randomization Study
Ardissino M, Slob E, Carter P, Rogne T, Girling J, Burgess S, Ng F. Sex‐Specific Reproductive Factors Augment Cardiovascular Disease Risk in Women: A Mendelian Randomization Study. Journal Of The American Heart Association 2023, 12: e027933. PMID: 36846989, PMCID: PMC10111460, DOI: 10.1161/jaha.122.027933.Peer-Reviewed Original ResearchConceptsCoronary artery diseaseBody mass indexHeart failureCardiovascular diseaseReproductive factorsArtery diseaseIschemic strokeMass indexAtrial fibrillationLive birthsFirst birthCardiovascular disease riskType 2 diabetesBackground Observational studiesMendelian randomizationMendelian randomization studyModifiable mediatorsBlood pressureResidual confoundingObservational studyPrimary analysisRandomization studyDisease riskStrokeClinical interventions
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