{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Trastulla L"],"funding":["Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)","British Heart Foundation","NIDA NIH HHS","NIA NIH HHS","NIDDK NIH HHS","Deutsche Forschungsgemeinschaft (German Research Foundation)","NIMH NIH HHS","Brain and Behavior Research Foundation (Brain & Behavior Research Foundation)","Bundesministerium für Wirtschaft und Energie (Federal Ministry for Economic Affairs and Energy)"],"pagination":["5534"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11217418"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["Stratified medicine holds great promise to tailor treatment to the needs of individual patients. While genetics holds great potential to aid patient stratification, it remains a major challenge to operationalize complex genetic risk factor profiles to deconstruct clinical heterogeneity. Contemporary approaches to this problem rely on polygenic risk scores (PRS), which provide only limited clinical utility and lack a clear biological foundation. To overcome these limitations, we develop the CASTom-iGEx approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue specific gene expression levels. The paradigmatic application of this approach to coronary artery disease or schizophrenia patient cohorts identified diverse strata or biotypes. The"],"journal":["Nature communications"],"pubmed_title":["Distinct genetic liability profiles define clinically relevant patient strata across common diseases."],"pmcid":["PMC11217418"],"funding_grant_id":["01EE1404H","DP3 DK111898","031L0174A","031L0174B","R01 MH097276","P01 AG002219","R37 MH057881","P50 MH084053","R01 MH085542","R01 MH109677","01EW 2009","R01 MH109897","01EW 2005","01ZX1904A","P50 AG005138","SCHU 1603/4-1, 5-1, 7-1; FA241/16-1","SFB TRR 267 (B05).","ZF4590201BA8","01ZX1706","P50 MH066392","01ZX1504","R01 MH080405","R01 MH075916","01ZX1614K","NARSAD Young Investigator Grant","SFB 1123 (B02)","U01 MH103392","HHSN271201300031C","R01 MH110921","81X2600522","R01 MH093725"],"pubmed_authors":["Domenici E","McCarley RW","Szatkiewicz JP","Tosato S","Kirov G","Catts SV","Strohmaier J","Frank J","Bruggeman R","Nertney DA","Lerer B","Esko T","Zai CC","Milani L","Demontis D","Black DW","Karachanak-Yankova S","Webb BT","Iorio F","Kalaydjieva L","Genovese G","Bigdeli TB","Kucinskiene ZA","von Scheidt M","Muller-Myhsok B","Scott RJ","Kahler AK","Georgieva L","Darvasi A","Giusti-Rodriguez P","Pantelis C","Thirumalai S","Wormley BK","Kendler KS","Weiser M","Williams S","Cantor RM","Neale BM","Cormican P","Rasmussen HB","Witt SH","Daly MJ","Jablensky AV","Klovins J","Petryshen TL","Gratten J","Henskens FA","Purcell SM","Sklar P","Zimprich F","Farrell MS","Mattheisen M","Van Os J","Davis KL","Liang KY","Chen RYL","Wildenauer DB","Dolgalev G","Essioux L","Cohen N","Lee SH","Hollegaard MV","Walters JTR","Hultman CM","Trastulla L","Olsen L","Holmans PA","Schulze TG","Wolen AR","Chambert KD","Agartz I","Cohen D","Myin-Germeys I","Clair DS","Joa I","Fanous AH","Drapeau E","Nothen MM","Budde M","Gill M","Lencz T","Loughland CM","Schall U","Andreassen OA","Carr VJ","Murphy KC","Cheung EFC","McDonald C","Bacanu SA","Belliveau RA","Bevilacqua E","Begemann M","Stroup TS","Melle I","Spencer CCA","Bramon E","Li M","Owen MJ","McCarroll SA","Sham PC","Li T","Nestadt G","Ikeda M","Freedman R","Reimers MA","Agerbo E","Eriksson J","Laurent C","Keller MC","Hougaard DM","Milanova V","Liu J","Maher BS","Paunio T","Wray NR","Ripke S","Reichenberg A","Cai G","Buxbaum JD","Toncheva D","Wong EHM","Kuzelova-Ptackova H","Straub RE","Chong SA","Djurovic S","Adolfsson R","O'Dushlaine C","Ziller MJ","Degenhardt F","Pietilainen O","Freimer NB","Dikeos D","Dudbridge F","Steinberg S","Maier W","Pulver AE","Homuth G","Kennedy JL","Metspalu A","Cahn W","Iwata N","McQuillin A","O'Callaghan E","Legge SE","Melegh B","Mowry BJ","Hansen T","Hirschhorn JN","Seidman LJ","Nordin A","Schwab SG","Soderman E","Limborska S","Jan Lubinski","Stahl EA","Hansen M","Lieberman J","Meijer CJ","Olincy A","Kahn RS","Volzke H","Goldstein JI","Cichon S","Khrunin A","Murray RM","Carrera N","Levinson DF","Palotie A","Sigurdsson E","Chen EYH","Waddington J","Walsh D","Jimenez-Barron LT","Marsal S","Mattingsdal M","Gejman PV","Pimm J","Sullivan PF","Albus M","Kucinskas V","Leboyer M","Zheng X","Bulik-Sullivan B","Visscher PM","Xi S","Corvin A","Papiol S","Magnusson PKE","Mallet J","Posthuma D","Haroutunian V","Ruderfer DM","Hoffmann P","O'Neill FA","Moser S","Cloninger CR","Franke L","Meier S","Morris DW","Mors O","O'Donovan MC","Buckner RL","Salomaa V","Hammer C","Amin F","Nenadic I","Cheng W","Julia A","Slominsky P","Mesholam-Gately RI","Powell J","Dan Rujescu","Eichhammer P","Hofman A","Herms S","Svrakic DM","Michie PT","Oh SY","Del Favero J","Bene J","Karjalainen J","Perkins DO","Strengman E","Macek M","Kavanagh D","Nicodemus KK","Nelis M","Scolnick EM","Parkhomenko E","Gurling H","Stogmann E","Campion D","Teumer A","Knight J","Pers TH","Kim Y","Price A","Farh KH","Nisenbaum L","Shi J","Pato C","Richards AL","Suvisaari J","Moran JL","Stefansson K","Huang H","Wang D","Hartmann AM","Rietschel M","de Haan L","Pocklington AJ","Stefansson H","Sanders AR","Smoller JW","Wang Q","Chan RCK","Schunkert H","Dinan T","Gopal S","Konte B","Godard S","Roussos P","Ophoff RA","Donohoe G","Mortensen PB","Hamshere ML","Heilbronner U","Nikitina-Zake L","Schizophrenia Working Group of the Psychiatric Genomics Consortium","Davidson M","Friedman JI","Gagneur J","Lee PH","Dorr M","Escott-Price V","Papadimitriou GN","Riley BP","Roffman JL","Knowles JA","Alexander M","Borglum AD","Buccola NG","Fromer M","Subramaniam M","Bergen SE","McIntosh AM","Andlauer TFM","Werge T","Falkai P","Li QS","Crowley JJ","Mokrab Y","So HC","Duan J","Sim K","Byerley W","Silverman JM","Blackwood DHR","Collier DA","Keong JLC","Malhotra AK","Treutlein J","Giegling I","Quested D","Williams NM","Craddock N","Lonnqvist J","Pato MT","Weinberger DR","Jonsson EG","Ehrenreich H"],"additional_accession":[]},"is_claimable":false,"name":"Distinct genetic liability profiles define clinically relevant patient strata across common diseases.","description":"Stratified medicine holds great promise to tailor treatment to the needs of individual patients. While genetics holds great potential to aid patient stratification, it remains a major challenge to operationalize complex genetic risk factor profiles to deconstruct clinical heterogeneity. Contemporary approaches to this problem rely on polygenic risk scores (PRS), which provide only limited clinical utility and lack a clear biological foundation. To overcome these limitations, we develop the CASTom-iGEx approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue specific gene expression levels. The paradigmatic application of this approach to coronary artery disease or schizophrenia patient cohorts identified diverse strata or biotypes. The","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2025-04-06T00:13:00.95Z","creation":"2025-04-06T00:13:00.95Z"},"accession":"S-EPMC11217418","cross_references":{"pubmed":["38951512"],"doi":["10.1038/s41467-024-49338-2"]}}