2024
Critical reasoning on the co-expression module QTL in the dorsolateral prefrontal cortex
Cote A, Young H, Huckins L. Critical reasoning on the co-expression module QTL in the dorsolateral prefrontal cortex. Human Genetics And Genomics Advances 2024, 5: 100311. PMID: 38773772, PMCID: PMC11214266, DOI: 10.1016/j.xhgg.2024.100311.Peer-Reviewed Original ResearchConceptsExpression quantitative trait lociGene co-expressionCo-expressionExpression quantitative trait locus methodGenetic variantsComplex trait heritabilityMultiple testing burdenGene-based testsQuantitative trait lociTrans-eQTLsCis-eQTLsRegulatory variationSequencing datasetsTrait lociGene regulationTrait heritabilityGene functionGene modulesReal-data applicationModule genesGenesTesting burdenDorsolateral prefrontal cortexVariantsComparison to prior studies
2023
Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations
Liu D, Meyer D, Fennessy B, Feng C, Cheng E, Johnson J, Park Y, Rieder M, Ascolillo S, de Pins A, Dobbyn A, Lebovitch D, Moya E, Nguyen T, Wilkins L, Hassan A, Burdick K, Buxbaum J, Domenici E, Frangou S, Hartmann A, Laurent-Levinson C, Malhotra D, Pato C, Pato M, Ressler K, Roussos P, Rujescu D, Arango C, Bertolino A, Blasi G, Bocchio-Chiavetto L, Campion D, Carr V, Fullerton J, Gennarelli M, González-Peñas J, Levinson D, Mowry B, Nimgaokar V, Pergola G, Rampino A, Cervilla J, Rivera M, Schwab S, Wildenauer D, Daly M, Neale B, Singh T, O’Donovan M, Owen M, Walters J, Ayub M, Malhotra A, Lencz T, Sullivan P, Sklar P, Stahl E, Huckins L, Charney A. Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations. Nature Genetics 2023, 55: 369-376. PMID: 36914870, PMCID: PMC10011128, DOI: 10.1038/s41588-023-01305-1.Peer-Reviewed Original ResearchConceptsProtein-truncating variantsRare protein-truncating variantsControls of diverse ancestryGenetic architecture of schizophreniaRare variant signalsProtein-coding regionsSchizophrenia risk genesCustom sequencing panelAncestral populationsAllelic spectrumGenetic architectureHuman populationDiverse ancestryHuman geneticsRisk genesVariant signalsGenesSequencing panelSchizophrenia casesSchizophrenia riskChronic mental illnessAncestryGeneticsMental illnessVariants
2022
Chapter 14 Integration with systems biology approaches and -omics data to characterize risk variation
Young H, Cote A, Huckins L. Chapter 14 Integration with systems biology approaches and -omics data to characterize risk variation. 2022, 289-315. DOI: 10.1016/b978-0-12-819602-1.00017-6.Peer-Reviewed Original ResearchAssociation studiesPatterns of linkage disequilibriumTranscriptome-wide association studyGenome-wide association studiesFunctional genomic annotationsSystems biology approachGenome annotationNoncoding variantsNoncoding regionsLinkage disequilibriumGene regulationRegulatory regionsGene networksGenetic variantsBiology approachFunctional pathwaysRisk variationDevelopmental stagesGenetic riskGenesPathwayUnique considerationsVariantsVariation researchPsychiatric disorders
2019
Synergistic effects of common schizophrenia risk variants
Schrode N, Ho SM, Yamamuro K, Dobbyn A, Huckins L, Matos MR, Cheng E, Deans PJM, Flaherty E, Barretto N, Topol A, Alganem K, Abadali S, Gregory J, Hoelzli E, Phatnani H, Singh V, Girish D, Aronow B, Mccullumsmith R, Hoffman GE, Stahl EA, Morishita H, Sklar P, Brennand KJ. Synergistic effects of common schizophrenia risk variants. Nature Genetics 2019, 51: 1475-1485. PMID: 31548722, PMCID: PMC6778520, DOI: 10.1038/s41588-019-0497-5.Peer-Reviewed Original ResearchMeSH KeywordsChloride ChannelsCRISPR-Cas SystemsFemaleFurinGene EditingGene Expression RegulationGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInduced Pluripotent Stem CellsMaleMonomeric Clathrin Assembly ProteinsPolymorphism, Single NucleotideQuantitative Trait LociSchizophreniaSNARE ProteinsConceptsExpression quantitative trait lociComplex genetic disorderEQTL genesCommon variantsQuantitative trait lociRisk variantsGene expression differencesPsychiatric disease riskCommon risk variantsPluripotent stem cellsSchizophrenia risk variantsGenetic disordersTrait lociGene perturbationsGenetic approachesExpression differencesGene editingStem cellsGeneralizable phenomenonSynaptic functionGenesVariantsCRISPRLociSpecific effectsGenetic Overlap Between Alzheimer’s Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes
Drange O, Smeland O, Shadrin A, Finseth P, Witoelar A, Frei O, Group P, Wang Y, Hassani S, Djurovic S, Dale A, Andreassen O, Stahl E, Breen G, Forstner A, McQuillin A, Ripke S, Trubetskoy V, Mattheisen M, Wang Y, Coleman J, Gaspar H, de Leeuw C, Steinberg S, Pavlides J, Trzaskowski M, Pers T, Holmans P, Abbott L, Agerbo E, Akil H, Albani D, Alliey-Rodriguez N, Als T, Anjorin A, Antilla V, Awasthi S, Badner J, Bækvad-Hansen M, Barchas J, Bass N, Bauer M, Belliveau R, Bergen S, Pedersen C, Bøen E, Boks M, Boocock J, Budde M, Bunney W, Burmeister M, Bybjerg-Grauholm J, Byerley W, Casas M, Cerrato F, Cervantes P, Chambert K, Charney A, Chen D, Churchhouse C, Clarke T, Coryell W, Craig D, Cruceanu C, Curtis D, Czerski P, Dale A, de Jong S, Degenhardt F, Del-Favero J, DePaulo J, Djurovic S, Dobbyn A, Dumont A, Elvsåshagen T, Escott-Price V, Fan C, Fischer S, Flickinger M, Foroud T, Forty L, Frank J, Fraser C, Freimer N, Friseìn L, Gade K, Gage D, Garnham J, Giambartolomei C, Pedersen M, Goldstein J, Gordon S, Gordon-Smith K, Green E, Green M, Greenwood T, Grove J, Guan W, Parra J, Hamshere M, Hautzinger M, Heilbronner U, Herms S, Hipolito M, Hoffmann P, Holland D, Huckins L, Jamain S, Johnson J, Jureìus A, Kandaswamy R, Karlsson R, Kennedy J, Kittel-Schneider S, Knott S, Knowles J, Kogevinas M, Koller A, Kupka R, Lavebratt C, Lawrence J, Lawson W, Leber M, Lee P, Levy S, Li J, Liu C, Lucae S, Maaser A, MacIntyre D, Mahon P, Maier W, Martinsson L, McCarroll S, McGuffin P, McInnis M, McKay J, Medeiros H, Medland S, Meng F, Milani L, Montgomery G, Morris D, Mühleisen T, Mullins N, Nguyen H, Nievergelt C, Adolfsson A, Nwulia E, O’Donovan C, Loohuis L, Ori A, Oruc L, Ösby U, Perlis R, Perry A, Pfennig A, Potash J, Purcell S, Regeer E, Reif A, Reinbold C, Rice J, Rivas F, Rivera M, Roussos P, Ruderfer D, Ryu E, Saìnchez-Mora C, Schatzberg A, Scheftner W, Schork N, Weickert C, Shehktman T, Shilling P, Sigurdsson E, Slaney C, Smeland O, Sobell J, Hansen C, Spijker A, St Clair D, Steffens M, Strauss J, Streit F, Strohmaier J, Szelinger S, Thompson R, Thorgeirsson T, Treutlein J, Vedder H, Wang W, Watson S, Weickert T, Witt S, Xi S, Xu W, Young A, Zandi P, Zhang P, Zollner S, Adolfsson R, Agartz I, Alda M, Backlund L, Baune B, Bellivier F, Berrettini W, Biernacka J, Blackwood D, Boehnke M, Børglum A, Corvin A, Craddock N, Daly M, Dannlowski U, Esko T, Etain B, Frye M, Fullerton J, Gershon E, Gill M, Goes F, Grigoroiu-Serbanescu M, Hauser J, Hougaard D, Hultman C, Jones I, Jones L, Kahn R, Kirov G, Landeìn M, Leboyer M, Lewis C, Li Q, Lissowska J, Martin N, Mayoral F, McElroy S, McIntosh A, McMahon F, Melle I, Metspalu A, Mitchell P, Morken G, Mors O, Mortensen P, Müller-Myhsok B, Myers R, Neale B, Nimgaonkar V, Nordentoft M, Nöthen M, O’Donovan M, Oedegaard K, Owen M, Paciga S, Pato C, Pato M, Posthuma D, Ramos-Quiroga J, Ribaseìs M, Rietschel M, Rouleau G, Schalling M, Schofield P, Schulze T, Serretti A, Smoller J, Stefansson H, Stefansson K, Stordal E, Sullivan P, Turecki G, Vaaler A, Vieta E, Vincent J, Werge T, Nurnberger J, Wray N, Di Florio A, Edenberg H, Cichon S, Ophoff R, Scott L, Andreassen O, Kelsoe J, Sklar P. Genetic Overlap Between Alzheimer’s Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes. Frontiers In Neuroscience 2019, 13: 220. PMID: 30930738, PMCID: PMC6425305, DOI: 10.3389/fnins.2019.00220.Peer-Reviewed Original ResearchCommon genetic variantsNovel lociGenetic variantsGenetic overlapPolygenic overlapGenome-wide associationNovel genomic lociNumerous common genetic variantsGenomic lociComplex traitsWide associationGenesLociInternational GenomicsGenetic originTraitsAlzheimer's diseaseImplicatingVariantsGenomicsOverlapBipolar disorderDistinct featuresFurther studies
2017
Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa
Huckins L, Hatzikotoulas K, Southam L, Thornton L, Steinberg J, Aguilera-McKay F, Treasure J, Schmidt U, Gunasinghe C, Romero A, Curtis C, Rhodes D, Moens J, Kalsi G, Dempster D, Leung R, Keohane A, Burghardt R, Ehrlich S, Hebebrand J, Hinney A, Ludolph A, Walton E, Deloukas P, Hofman A, Palotie A, Palta P, van Rooij F, Stirrups K, Adan R, Boni C, Cone R, Dedoussis G, van Furth E, Gonidakis F, Gorwood P, Hudson J, Kaprio J, Kas M, Keski-Rahonen A, Kiezebrink K, Knudsen G, Slof-Op 't Landt M, Maj M, Monteleone A, Monteleone P, Raevuori A, Reichborn-Kjennerud T, Tozzi F, Tsitsika A, van Elburg A, Collier D, Sullivan P, Breen G, Bulik C, Zeggini E. Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa. Molecular Psychiatry 2017, 23: 1169-1180. PMID: 29155802, PMCID: PMC5828108, DOI: 10.1038/mp.2017.88.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significanceGenomic search spaceGenome-wide variationLow-frequency variantsDetect low-frequency variantsPopulations of European originDe novo replicationIntergenic variantVariant associationsExome-chipAssociation studiesIntronic variantsRare variantsIn silicoEuropean originVariantsEffect sizeLociOPCMLWell-poweredSilicoReplicationNeuropsychiatric disorders
2014
Using ancestry-informative markers to identify fine structure across 15 populations of European origin
Huckins L, Boraska V, Franklin C, Floyd J, Southam L, Sullivan P, Bulik C, Collier D, Tyler-Smith C, Zeggini E, Tachmazidou I. Using ancestry-informative markers to identify fine structure across 15 populations of European origin. European Journal Of Human Genetics 2014, 22: 1190-1200. PMID: 24549058, PMCID: PMC4169539, DOI: 10.1038/ejhg.2014.1.Peer-Reviewed Original ResearchConceptsMinor allele frequencyPopulations of European originGenome-wide association scanAncestry-informative markersEuropean-descent populationsAxes of variationEuropean originGenetic structureAssociation scansPopulation structurePopulation stratificationK chipAllele frequenciesAssociation resultsSNPsInformative axesIlluminaMarkersPopulationVariantsPrincipal component analysisConsortiaComparative methodOriginWellcome