2024
Shared Genetic Architecture Between Schizophrenia and Anorexia Nervosa: A Cross-trait Genome-Wide Analysis
Lu Z, Ploner A, Birgegård A, Adan R, Alfredsson L, Ando T, Andreassen O, Baker J, Bergen A, Berrettini W, Birgegård A, Boden J, Boehm I, Perica V, Brandt H, Breen G, Bryois J, Buehren K, Bulik C, Burghardt R, Cassina M, Cichon S, Coleman J, Cone R, Courtet P, Crawford S, Crow S, Crowley J, Danner U, Davis O, de Zwaan M, Dedoussis G, DeSocio J, Dick D, Dikeos D, Dina C, Dmitrzak-Weglarz M, Docampo E, Duncan L, Egberts K, Ehrlich S, Escaramís G, Esko T, Estivill X, Farmer A, Favaro A, Fernández-Aranda F, Fischer K, Föcker M, Foretova L, Forstner A, Forzan M, Franklin C, Gallinger S, Giegling I, Giusti-Rodríguez P, Gonidakis F, Gordon S, Gorwood P, Mayora M, Grove J, Guillaume S, Guo Y, Hakonarson H, Halmi K, Hanscombe K, Hatzikotoulas K, Hauser J, Hebebrand J, Helder S, Herms S, Herpertz-Dahlmann B, Herzog W, Hinney A, Horwood L, Hübel C, Huckins L, Hudson J, Imgart H, Inoko H, Janout V, Jiménez-Murcia S, Johnson C, Jordan J, Julià A, Kalsi G, Kaminská D, Kaplan A, Kaprio J, Karhunen L, Karwautz A, Kas M, Kaye W, Kennedy J, Kennedy M, Keski-Rahkonen A, Kiezebrink K, Kim Y, Klareskog L, Klump K, Landén M, Larsen J, Le Hellard S, Leppä V, Li D, Lichtenstein P, Lilenfeld L, Lin B, Lissowska J, Luykx J, Maj M, Marsal S, Martin N, Mattheisen M, Mattingsdal M, Medland S, Metspalu A, Meulenbelt I, Micali N, Mitchell K, Mitchell J, Monteleone A, Monteleone P, Mortensen P, Munn-Chernoff M, Nacmias B, Navratilova M, Ntalla I, Olsen C, Ophoff R, Padyukov L, Pantel J, Papezova H, Parker R, Pearson J, Pedersen N, Petersen L, Pinto D, Purves K, Raevuori A, Ramoz N, Reichborn-Kjennerud T, Ricca V, Ripatti S, Ripke S, Ritschel F, Roberts M, Rujescu D, Rybakowski F, Santonastaso P, Scherag A, Scherer S, Schmidt U, Schork N, Schosser A, Seitz J, Slachtova L, Slagboom P, Landt M, Slopien A, Sorbi S, Strober M, Sullivan P, Świątkowska B, Szatkiewicz J, Tenconi E, Thornton L, Tortorella A, Treasure J, Tsitsika A, Tyszkiewicz-Nwafor M, van Elburg A, van Furth E, Wade T, Wagner G, Watson H, Werge T, Whiteman D, Widen E, Woodside D, Yao S, Yilmaz Z, Zeggini E, Zerwas S, Zipfel S, Breen G, Bulik C, Bulik C, Bergen S. Shared Genetic Architecture Between Schizophrenia and Anorexia Nervosa: A Cross-trait Genome-Wide Analysis. Schizophrenia Bulletin 2024, 50: 1255-1265. PMID: 38848516, PMCID: PMC11349005, DOI: 10.1093/schbul/sbae087.Peer-Reviewed Original ResearchPolygenic overlapConditional/conjunctional false discovery rateGenome-wide association studiesGenome-wide analysisConcordant effect directionsProportion of variantsNovel lociFalse discovery rateFunctional annotationGenetic architectureGenetic enrichmentAssociation studiesMultiple genesSynapse organizationMendelian randomization analysisGenetic associationCo-aggregationLociGenetic componentGenetic etiologyAnorexia nervosaFamilial co-aggregationDiscovery rateGenetic factorsRandomization analysis
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
2021
Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits
Martin J, Khramtsova E, Goleva S, Blokland G, Traglia M, Walters R, Hübel C, Coleman J, Breen G, Børglum A, Demontis D, Grove J, Werge T, Bralten J, Bulik C, Lee P, Mathews C, Peterson R, Winham S, Wray N, Edenberg H, Guo W, Yao Y, Neale B, Faraone S, Petryshen T, Weiss L, Duncan L, Goldstein J, Smoller J, Stranger B, Davis L, Consortium S, Alda M, Bortolato M, Burton C, Byrne E, Carey C, Erdman L, Huckins L, Mattheisen M, Robinson E, Stahl E. Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits. Biological Psychiatry 2021, 89: 1127-1137. PMID: 33648717, PMCID: PMC8163257, DOI: 10.1016/j.biopsych.2020.12.024.Peer-Reviewed Original ResearchConceptsSex-differential effectsSex differencesGenetic architectureBehavioral traitsSingle nucleotide polymorphism (SNP)-based heritabilityGenetic correlationsGenome-wide association summary statisticsSNP-based heritabilityMultiple gene setsOrigins of sex differencesAssociation summary statisticsIdentified 4 genesGene-based approachRisk-taking behaviorIdentified genesGene setsWell-powered studiesBehavioral phenotypesBiological functionsGenetic contributionBetween-sexGenetic effectsTrait pairsGenetic correlation estimatesNeuron-related
2019
Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
Watson H, Yilmaz Z, Thornton L, Hübel C, Coleman J, Gaspar H, Bryois J, Hinney A, Leppä V, Mattheisen M, Medland S, Ripke S, Yao S, Giusti-Rodríguez P, Hanscombe K, Purves K, Adan R, Alfredsson L, Ando T, Andreassen O, Baker J, Berrettini W, Boehm I, Boni C, Perica V, Buehren K, Burghardt R, Cassina M, Cichon S, Clementi M, Cone R, Courtet P, Crow S, Crowley J, Danner U, Davis O, de Zwaan M, Dedoussis G, Degortes D, DeSocio J, Dick D, Dikeos D, Dina C, Dmitrzak-Weglarz M, Docampo E, Duncan L, Egberts K, Ehrlich S, Escaramís G, Esko T, Estivill X, Farmer A, Favaro A, Fernández-Aranda F, Fichter M, Fischer K, Föcker M, Foretova L, Forstner A, Forzan M, Franklin C, Gallinger S, Giegling I, Giuranna J, Gonidakis F, Gorwood P, Mayora M, Guillaume S, Guo Y, Hakonarson H, Hatzikotoulas K, Hauser J, Hebebrand J, Helder S, Herms S, Herpertz-Dahlmann B, Herzog W, Huckins L, Hudson J, Imgart H, Inoko H, Janout V, Jiménez-Murcia S, Julià A, Kalsi G, Kaminská D, Kaprio J, Karhunen L, Karwautz A, Kas M, Kennedy J, Keski-Rahkonen A, Kiezebrink K, Kim Y, Klareskog L, Klump K, Knudsen G, La Via M, Le Hellard S, Levitan R, Li D, Lilenfeld L, Lin B, Lissowska J, Luykx J, Magistretti P, Maj M, Mannik K, Marsal S, Marshall C, Mattingsdal M, McDevitt S, McGuffin P, Metspalu A, Meulenbelt I, Micali N, Mitchell K, Monteleone A, Monteleone P, Munn-Chernoff M, Nacmias B, Navratilova M, Ntalla I, O’Toole J, Ophoff R, Padyukov L, Palotie A, Pantel J, Papezova H, Pinto D, Rabionet R, Raevuori A, Ramoz N, Reichborn-Kjennerud T, Ricca V, Ripatti S, Ritschel F, Roberts M, Rotondo A, Rujescu D, Rybakowski F, Santonastaso P, Scherag A, Scherer S, Schmidt U, Schork N, Schosser A, Seitz J, Slachtova L, Slagboom P, Slof-Op ‘t Landt M, Slopien A, Sorbi S, Świątkowska B, Szatkiewicz J, Tachmazidou I, Tenconi E, Tortorella A, Tozzi F, Treasure J, Tsitsika A, Tyszkiewicz-Nwafor M, Tziouvas K, van Elburg A, van Furth E, Wagner G, Walton E, Widen E, Zeggini E, Zerwas S, Zipfel S, Bergen A, Boden J, Brandt H, Crawford S, Halmi K, Horwood L, Johnson C, Kaplan A, Kaye W, Mitchell J, Olsen C, Pearson J, Pedersen N, Strober M, Werge T, Whiteman D, Woodside D, Stuber G, Gordon S, Grove J, Henders A, Juréus A, Kirk K, Larsen J, Parker R, Petersen L, Jordan J, Kennedy M, Montgomery G, Wade T, Birgegård A, Lichtenstein P, Norring C, Landén M, Martin N, Mortensen P, Sullivan P, Breen G, Bulik C. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nature Genetics 2019, 51: 1207-1214. PMID: 31308545, PMCID: PMC6779477, DOI: 10.1038/s41588-019-0439-2.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesTwin-based heritability estimatesEating Disorders Working GroupPsychiatric Genomics ConsortiumAnorexia nervosaBody-mass indexSignificant lociGenetic architectureRisk lociGenetics InitiativeGenomics ConsortiumLow body-mass indexMetabo-psychiatric disorderGenetic correlationsMetabolic componentsLociCases of anorexia nervosaPhysical activityAnthropometric traitsPsychiatric disordersHeritability estimatesAnorexia Nervosa Genetics InitiativeNervosaImprove outcomesGenetic analyses of diverse populations improves discovery for complex traits
Wojcik G, Graff M, Nishimura K, Tao R, Haessler J, Gignoux C, Highland H, Patel Y, Sorokin E, Avery C, Belbin G, Bien S, Cheng I, Cullina S, Hodonsky C, Hu Y, Huckins L, Jeff J, Justice A, Kocarnik J, Lim U, Lin B, Lu Y, Nelson S, Park S, Poisner H, Preuss M, Richard M, Schurmann C, Setiawan V, Sockell A, Vahi K, Verbanck M, Vishnu A, Walker R, Young K, Zubair N, Acuña-Alonso V, Ambite J, Barnes K, Boerwinkle E, Bottinger E, Bustamante C, Caberto C, Canizales-Quinteros S, Conomos M, Deelman E, Do R, Doheny K, Fernández-Rhodes L, Fornage M, Hailu B, Heiss G, Henn B, Hindorff L, Jackson R, Laurie C, Laurie C, Li Y, Lin D, Moreno-Estrada A, Nadkarni G, Norman P, Pooler L, Reiner A, Romm J, Sabatti C, Sandoval K, Sheng X, Stahl E, Stram D, Thornton T, Wassel C, Wilkens L, Winkler C, Yoneyama S, Buyske S, Haiman C, Kooperberg C, Le Marchand L, Loos R, Matise T, North K, Peters U, Kenny E, Carlson C. Genetic analyses of diverse populations improves discovery for complex traits. Nature 2019, 570: 514-518. PMID: 31217584, PMCID: PMC6785182, DOI: 10.1038/s41586-019-1310-4.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesComplex traitsBiology of complex traitsDiverse populationsEvidence of effect-size heterogeneityGenome-wide effortsLarge-scale genomic studiesReduce health disparitiesNon-European individualsHighest burden of diseaseMulti-ethnic participantsEffect-size heterogeneityBurden of diseaseRepresentation of diverse populationsGWAS associationsNovel lociRisk prediction scoreAdmixed populationsFine-mappingGenetic architectureAssociation studiesGenomic studiesHealth disparitiesHealthcare disparitiesPopulation Architecture
2018
Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection
Pardiñas A, Holmans P, Pocklington A, Escott-Price V, Ripke S, Carrera N, Legge S, Bishop S, Cameron D, Hamshere M, Han J, Hubbard L, Lynham A, Mantripragada K, Rees E, MacCabe J, McCarroll S, Baune B, Breen G, Byrne E, Dannlowski U, Eley T, Hayward C, Martin N, McIntosh A, Plomin R, Porteous D, Wray N, Caballero A, Geschwind D, Huckins L, Ruderfer D, Santiago E, Sklar P, Stahl E, Won H, Agerbo E, Als T, Andreassen O, Bækvad-Hansen M, Mortensen P, Pedersen C, Børglum A, Bybjerg-Grauholm J, Djurovic S, Durmishi N, Pedersen M, Golimbet V, Grove J, Hougaard D, Mattheisen M, Molden E, Mors O, Nordentoft M, Pejovic-Milovancevic M, Sigurdsson E, Silagadze T, Hansen C, Stefansson K, Stefansson H, Steinberg S, Tosato S, Werge T, GERAD1 Consortium, CRESTAR Consortium, Collier D, Rujescu D, Kirov G, Owen M, O’Donovan M, Walters J. Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nature Genetics 2018, 50: 381-389. PMID: 29483656, PMCID: PMC5918692, DOI: 10.1038/s41588-018-0059-2.Peer-Reviewed Original ResearchConceptsMutation-intolerant genesGenetic architecture of schizophreniaGenome-wide association studiesChromosome conformation dataGenome fine mappingVariant association signalsAssociation signalsFine-mappingGenetic architectureCausal genesGenomic studiesAssociation studiesRisk variantsSelection pressureGenesLociBrain expressionAssociated with poor qualityBiologyConformational dataDecreased life expectancyChromosomeDebilitating psychiatric conditionAllelesLife expectancy
2017
Integrated Bayesian analysis of rare exonic variants to identify risk genes for schizophrenia and neurodevelopmental disorders
Nguyen H, Bryois J, Kim A, Dobbyn A, Huckins L, Munoz-Manchado A, Ruderfer D, Genovese G, Fromer M, Xu X, Pinto D, Linnarsson S, Verhage M, Smit A, Hjerling-Leffler J, Buxbaum J, Hultman C, Sklar P, Purcell S, Lage K, He X, Sullivan P, Stahl E. Integrated Bayesian analysis of rare exonic variants to identify risk genes for schizophrenia and neurodevelopmental disorders. Genome Medicine 2017, 9: 114. PMID: 29262854, PMCID: PMC5738153, DOI: 10.1186/s13073-017-0497-y.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsDD risk genesRisk genesRisk-geneGene set enrichment resultsProtein-protein interaction subnetworksStudy of rare variationWhole-exome sequencing dataNeurodevelopmental disorder genesPost-transcriptional gene regulationExome sequencing dataSets of genesRare exonic variantsGene set enrichmentRare variationNeurodevelopmental disordersAutism spectrum disorderGene subnetworksGenetic architectureSequence dataRNA-seqTrio familiesGene regulationExonic variantsPathway enrichment