2021
Genome-wide association study of stimulant dependence
Cox J, Sherva R, Wetherill L, Foroud T, Edenberg HJ, Kranzler HR, Gelernter J, Farrer LA. Genome-wide association study of stimulant dependence. Translational Psychiatry 2021, 11: 363. PMID: 34226506, PMCID: PMC8257618, DOI: 10.1038/s41398-021-01440-5.Peer-Reviewed Original ResearchConceptsStimulant dependenceAssociation studiesVoltage-gated channel proteinsGenome-wide association studiesNicotinic acetylcholine receptor genesTop GWAS signalsUse disordersAcetylcholine receptor genesWide association studyGWAS signalsSubstance use disordersEuropean ancestry subjectsNovel genesCocaine use disorderUsers of cocaineChannel proteinsGenetic studiesSpecific genetic factorsGenetics of AlcoholismSignificant pleiotropy
2017
Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence
Hancock DB, Guo Y, Reginsson GW, Gaddis NC, Lutz SM, Sherva R, Loukola A, Minica CC, Markunas CA, Han Y, Young KA, Gudbjartsson DF, Gu F, McNeil DW, Qaiser B, Glasheen C, Olson S, Landi MT, Madden PAF, Farrer LA, Vink J, Saccone NL, Neale MC, Kranzler HR, McKay J, Hung RJ, Amos CI, Marazita ML, Boomsma DI, Baker TB, Gelernter J, Kaprio J, Caporaso NE, Thorgeirsson TE, Hokanson JE, Bierut LJ, Stefansson K, Johnson EO. Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence. Molecular Psychiatry 2017, 23: 1911-1919. PMID: 28972577, PMCID: PMC5882602, DOI: 10.1038/mp.2017.193.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesGenotype-Tissue Expression (GTEx) projectDNA methyltransferase genesAcetylcholine receptor genesNicotine dependenceMethyltransferase geneExpression projectCHRNB4 genesHeritable traitAdditional lociProxy phenotypeSequence variantsDNMT3B expressionGenesReceptor geneSquamous cell lung carcinomaCHRNA5-CHRNA3African American ancestryNovel associationsInternational Lung Cancer ConsortiumCell lung carcinomaLociAmerican ancestryAdult cerebellum
2016
CHRNA5/A3/B4 Variant rs3743078 and Nicotine-Related Phenotypes: Indirect Effects Through Nicotine Craving.
Shmulewitz D, Meyers JL, Wall MM, Aharonovich E, Frisch A, Spivak B, Weizman A, Edenberg HJ, Gelernter J, Hasin DS. CHRNA5/A3/B4 Variant rs3743078 and Nicotine-Related Phenotypes: Indirect Effects Through Nicotine Craving. Journal Of Studies On Alcohol And Drugs 2016, 77: 227-37. PMID: 26997181, PMCID: PMC4803655, DOI: 10.15288/jsad.2016.77.227.Peer-Reviewed Original ResearchConceptsNicotine cravingFTND scoreNeuronal nicotinic acetylcholine receptor geneNicotine use disorderNicotinic acetylcholine receptor genesAcetylcholine receptor genesLifetime smokersCigarette smokingMore cigarettesHigher scoresNicotine dependenceFagerström TestTherapeutic targetUse disordersG alleleAllele GCHRNA5-CHRNA3CravingReceptor geneScoresSizeable proportionFTNDCigarettesHousehold sampleSignificant indirect effect
2013
Distinct Loci in the CHRNA5/CHRNA3/CHRNB4 Gene Cluster Are Associated With Onset of Regular Smoking
Stephens SH, Hartz SM, Hoft NR, Saccone NL, Corley RC, Hewitt JK, Hopfer CJ, Breslau N, Coon H, Chen X, Ducci F, Dueker N, Franceschini N, Frank J, Han Y, Hansel NN, Jiang C, Korhonen T, Lind PA, Liu J, Lyytikäinen L, Michel M, Shaffer JR, Short SE, Sun J, Teumer A, Thompson JR, Vogelzangs N, Vink JM, Wenzlaff A, Wheeler W, Yang B, Aggen SH, Balmforth AJ, Baumeister SE, Beaty TH, Benjamin DJ, Bergen AW, Broms U, Cesarini D, Chatterjee N, Chen J, Cheng Y, Cichon S, Couper D, Cucca F, Dick D, Foroud T, Furberg H, Giegling I, Gillespie NA, Gu F, Hall AS, Hällfors J, Han S, Hartmann AM, Heikkilä K, Hickie IB, Hottenga JJ, Jousilahti P, Kaakinen M, Kähönen M, Koellinger PD, Kittner S, Konte B, Landi M, Laatikainen T, Leppert M, Levy SM, Mathias RA, McNeil DW, Medland SE, Montgomery GW, Murray T, Nauck M, North KE, Paré PD, Pergadia M, Ruczinski I, Salomaa V, Viikari J, Willemsen G, Barnes KC, Boerwinkle E, Boomsma DI, Caporaso N, Edenberg HJ, Francks C, Gelernter J, Grabe HJ, Hops H, Jarvelin M, Johannesson M, Kendler KS, Lehtimäki T, Magnusson PK, Marazita ML, Marchini J, Mitchell BD, Nöthen MM, Penninx BW, Raitakari O, Rietschel M, Rujescu D, Samani NJ, Schwartz AG, Shete S, Spitz M, Swan GE, Völzke H, Veijola J, Wei Q, Amos C, Cannon DS, Grucza R, Hatsukami D, Heath A, Johnson EO, Kaprio J, Madden P, Martin NG, Stevens VL, Weiss RB, Kraft P, Bierut LJ, Ehringer MA. Distinct Loci in the CHRNA5/CHRNA3/CHRNB4 Gene Cluster Are Associated With Onset of Regular Smoking. Genetic Epidemiology 2013, 37: 846-859. PMID: 24186853, PMCID: PMC3947535, DOI: 10.1002/gepi.21760.Peer-Reviewed Original ResearchConceptsGene clusterAssociation signalsEarly smoking behaviourSmoking behaviorCHRNA5/A3/B4 gene clusterNicotinic acetylcholine receptor genesRobust association signalsNeuronal nicotinic acetylcholine receptor geneAcetylcholine receptor genesNicotine dependenceCHRNB4 gene clusterSignificant associationB4 gene clusterDistinct lociLung cancer riskRegular tobacco useAssociation resultsNicotine dependence phenotypesDependence phenotypesReceptor geneCotinine levelsRs1948PhenotypeRegular smokingProtective effect
2011
Childhood Adversity Increases Risk for Nicotine Dependence and Interacts with α5 Nicotinic Acetylcholine Receptor Genotype Specifically in Males
Xie P, Kranzler HR, Zhang H, Oslin D, Anton RF, Farrer LA, Gelernter J. Childhood Adversity Increases Risk for Nicotine Dependence and Interacts with α5 Nicotinic Acetylcholine Receptor Genotype Specifically in Males. Neuropsychopharmacology 2011, 37: 669-676. PMID: 22012472, PMCID: PMC3260970, DOI: 10.1038/npp.2011.240.Peer-Reviewed Original ResearchConceptsChildhood adversityRs16969968 genotypeND riskSex differencesNicotinic acetylcholine receptor genesAcetylcholine receptor genesPotential sex differencesNicotine dependence riskFagerstrom TestNicotine intakeSmoking riskIncrease riskNicotine dependenceRodent modelsReceptor genotypeND scoresEarly life experiencesEuropean AmericansReceptor geneWomenRiskGene × environment effectsMen
2010
Variation in Nicotinic Acetylcholine Receptor Genes is Associated with Multiple Substance Dependence Phenotypes
Sherva R, Kranzler HR, Yu Y, Logue MW, Poling J, Arias AJ, Anton RF, Oslin D, Farrer LA, Gelernter J. Variation in Nicotinic Acetylcholine Receptor Genes is Associated with Multiple Substance Dependence Phenotypes. Neuropsychopharmacology 2010, 35: 1921-1931. PMID: 20485328, PMCID: PMC3055642, DOI: 10.1038/npp.2010.64.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlack or African AmericanChromosomes, Human, Pair 15Family HealthFemaleGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansLinkage DisequilibriumMaleMiddle AgedPhenotypePolymorphism, Single NucleotideReceptors, NicotinicSubstance-Related DisordersWhite PeopleConceptsGene clusterAssociation studiesNicotinic receptor gene clusterNicotinic acetylcholine receptor genesAcetylcholine receptor genesReceptor gene clusterStrongest association signalSubstance dependence phenotypesAssociation signalsImportance of variationChromosome 15q25.1Opposite risk allelePermutation-based correctionDependence phenotypesReplication setReceptor geneMultiple polymorphismsSNPs