2021
Genetic associations for two biological age measures point to distinct aging phenotypes
Kuo C, Pilling LC, Liu Z, Atkins JL, Levine ME. Genetic associations for two biological age measures point to distinct aging phenotypes. Aging Cell 2021, 20: e13376. PMID: 34038024, PMCID: PMC8208797, DOI: 10.1111/acel.13376.Peer-Reviewed Original ResearchConceptsGenome-wide association scansAssociation scanEuropean descent participantsHomeostasis pathwaysPathway enrichmentAging phenotypesGenesGenetic associationCell functionStrong signalBiological age measuresPathwayUK BiobankGenetic predispositionClinical biochemistry markersImmune systemEnrichmentSNPsPhenotypeAPOE geneLipidsPredispositionDomainMarkers
2017
A Weighted SNP Correlation Network Method for Estimating Polygenic Risk Scores
Levine ME, Langfelder P, Horvath S. A Weighted SNP Correlation Network Method for Estimating Polygenic Risk Scores. Methods In Molecular Biology 2017, 1613: 277-290. PMID: 28849564, PMCID: PMC5998804, DOI: 10.1007/978-1-4939-7027-8_10.Peer-Reviewed Original ResearchMeSH KeywordsBody HeightComputational BiologyDatabases, GeneticGene Regulatory NetworksGenome-Wide Association StudyHumansMultifactorial InheritancePolymorphism, Single NucleotideUnited StatesWhite PeopleConceptsComplex traitsHuman heightCorrelation network analysisPolygenic score methodsPolygenic scoresSNP networkGWAS dataHub genesBiological insightsGenetic markersAllele countsGenetic pleiotropyTraitsGene scoreBiologyNetwork analysisPolygenic risk scoresNetwork-based methodPleiotropyGenesEnvironmental effectsSNPsPathwayLarge proportionDeeper understandingGenetic architecture of epigenetic and neuronal ageing rates in human brain regions
Lu AT, Hannon E, Levine ME, Crimmins EM, Lunnon K, Mill J, Geschwind DH, Horvath S. Genetic architecture of epigenetic and neuronal ageing rates in human brain regions. Nature Communications 2017, 8: 15353. PMID: 28516910, PMCID: PMC5454371, DOI: 10.1038/ncomms15353.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAgingBrainBrain MappingCalcium-Binding ProteinsChildChild, PreschoolCognitive DysfunctionDNA MethylationEpigenesis, GeneticFemaleGenome, HumanGenome-Wide Association StudyHumansInfantMaleMiddle AgedNerve Tissue ProteinsNeurodegenerative DiseasesNeuronsQuantitative Trait LociConceptsGenome-wide association studiesCis-expression quantitative trait lociGenome-wide significant lociProportion of neuronsQuantitative trait lociEpigenetic aging ratesDNA methylation-based biomarkersEpigenetic agingMethylation-based biomarkersGenetic architectureTrait lociSignificant lociAssociation studiesBrain regionsAge-related macular degenerationType 2 diabetesAging rateGenesLociHuman brain regionsUlcerative colitisWaist circumferenceMacular degenerationParkinson's diseaseBrain samples
2016
Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum
Lu AT, Hannon E, Levine ME, Hao K, Crimmins EM, Lunnon K, Kozlenkov A, Mill J, Dracheva S, Horvath S. Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum. Nature Communications 2016, 7: 10561. PMID: 26830004, PMCID: PMC4740877, DOI: 10.1038/ncomms10561.Peer-Reviewed Original ResearchConceptsWide association studyCis-acting effectsDNA methylation levelsAge-related diseasesGWAS analysisSignificant SNPsGene setsMLST8Association studiesEpigenetic clocksMethylation levelsEpigenetic biomarkersGenetic variantsExpression levelsSNPsUnderstanding agingEpigenetic ageTissue ageCerebellar samplesSignificant overlapGWASLociAlzheimer's diseaseClockVariants
2015
A Genetic Network Associated With Stress Resistance, Longevity, and Cancer in Humans
Levine ME, Crimmins EM. A Genetic Network Associated With Stress Resistance, Longevity, and Cancer in Humans. The Journals Of Gerontology Series A 2015, 71: 703-712. PMID: 26355015, PMCID: PMC4888382, DOI: 10.1093/gerona/glv141.Peer-Reviewed Original ResearchConceptsFunctional interaction networkSingle nucleotide polymorphismsStress resistanceNucleotide polymorphismsInteraction networksGenome-wide association studiesPathway analysisAssociation studiesPolygenic risk scoresNetworks AssociatedBiological networksHuman longevityUnique phenotypeHuman agingGenesPolymorphismLongevityPhenotypeInnate resilienceRisk scoreAge 52Threefold increasePathwayWeighted polygenic risk scoreResistance
2014
A Polygenic Risk Score Associated with Measures of Depressive Symptoms Among Older Adults
Levine ME, Crimmins EM, Prescott CA, Phillips D, Arpawong TE, Lee J. A Polygenic Risk Score Associated with Measures of Depressive Symptoms Among Older Adults. Biodemography And Social Biology 2014, 60: 199-211. PMID: 25343367, PMCID: PMC4298361, DOI: 10.1080/19485565.2014.952705.Peer-Reviewed Original ResearchConceptsHigher CESD scoresPolygenic risk scoresCESD scoresDepressive symptomsEpidemiological Studies Depression Scale scoreWeighted polygenic risk scoreLogistic regression modelsReplication sampleMultinomial logistic regression modelsRisk scoreScale scoreDiscovery setIndividual susceptibilitySymptomsOlder adultsAnalytic sampleGenetic riskSingle nucleotide polymorphismsScoresRetirement StudyRegression modelsDepressionPercent increaseAssociationHigh levels