Fine-mapping genomic loci refines bipolar disorder risk genes

Bipolar disorder is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 bipolar disorder risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods...

Descripción completa

Detalles Bibliográficos
Autores: Koromina, Maria|||0000-0001-8843-082X, Ravi, Ashvin, Panagiotaropoulou, Georgia, Schilder, Brian M.|||0000-0001-5949-2191, Humphrey, Jack, Braun, Alice|||0000-0003-1145-0261, Bigdeli, Tim B.|||0000-0003-2215-5946, Chatzinakos, Chris, Coombes, Brandon J.|||0000-0003-4322-5923, Kim, Jaeyoung|||0000-0001-6983-7907, Liu, Xiaoxi|||0000-0002-1933-8613, Terao, Chikashi|||0000-0002-6452-4095, O'Connell, Kevin S.|||0000-0002-6865-8795, Adams, Mark J, Adolfsson, Rolf, Alda, Martin|||0000-0001-9544-3944, Alfredsson, Lars|||0000-0003-1688-6697, Andlauer, Till F. M.|||0000-0002-2917-5889, Andreassen, Ole A.|||0000-0002-4461-3568, Antoniou, Anastasia, Baune, Bernhard T.|||0000-0001-6548-426X, Bengesser, Susanne, Biernacka, Joanna, Boehnke, Michael|||0000-0002-6442-7754, Bosch, Rosa|||0000-0002-7596-183X, Cairns, Murray J., Carr, Vaughan J., Casas Brugué, Miquel|||0000-0003-3496-8522, Catts, Stanley, Cichon, Sven|||0000-0002-9475-086X, Corvin, Aiden, Craddock, Nicholas, Dafnas, Konstantinos, Dalkner, Nina, Dannlowski, Udo|||0000-0002-0623-3759, Degenhardt, Franziska, Di Florio, Arianna, Dikeos, Dimitris, Fellendorf, Frederike Tabea, Ferentinos, Panagiotis|||0000-0001-8531-5623, Forstner, Andreas J., Forty, Liz|||0000-0002-4349-8414, Frye, Mark, Fullerton, Janice M.|||0000-0003-4014-4490, Gawlik, Micha, Gizer, Ian R., Gordon-Smith, Katherine, Green, Melissa J., Grigoroiu-Serbanescu, Maria, Guzman-Parra, Jose|||0000-0002-1463-6435, Hahn, Tim|||0000-0002-8929-4134, Henskens, Frans, Hillert, Jan|||0000-0002-7386-6732, Jablensky, Assen V., Jones, Lisa|||0000-0002-5122-8334, Jones, Ian, Jonsson, Lina, Kelsoe, John R., Kircher, Tilo|||0000-0002-2514-2625, Kirov, George|||0000-0002-3427-3950, Kittel-Schneider, Sarah|||0000-0003-3057-6150, Kogevinas, Manolis|||0000-0002-9605-0461, Landén, Mikael|||0000-0002-4496-6451, Leboyer, Marion|||0000-0001-5473-3697, Lenger, Melanie, Lissowska, Jolanta, Lochner, Christine|||0000-0002-4766-3704, Loughland, Carmel, MacIntyre, Donald J.|||0000-0001-6963-1335, Martin, Nicholas G.|||0000-0003-4069-8020, Maratou, Eirini, Mathews, Carol A.|||0000-0003-2208-7058, Mayoral-Cleries, Fermín, McElroy, Susan L., McGregor, Nathaniel|||0000-0001-7195-4993, McIntosh, Andrew M.|||0000-0002-0198-4588, McQuillin, Andrew|||0000-0003-1567-2240, Michie, Patricia|||0000-0002-4169-8519, Mitchell, Philip B., Moutsatsou, Paraskevi, Mowry, Bryan J.|||0000-0002-4115-5645, Müller-Myhsok, Bertram, Myers, Richard M., Nenadić, Igor|||0000-0002-0749-7473, Nievergelt, Caroline M., Nöthen, Markus M.|||0000-0002-8770-2464, Nurnberger, John, O'Donovan, Michael C.|||0000-0001-7073-2379, 'Donovan, Claire O., Ophoff, Roel A., Owen, Michael J., Pantelis, Christos|||0000-0002-9565-0238, Pato, Carlos|||0000-0002-5858-266X, Pato, Michele T., Patrinos, George P., Pawlak, Joanna M., Perlis, Roy H.|||0000-0002-5862-6757, Porichi, Evgenia, Posthuma, Danielle|||0000-0001-7582-2365, Ramos-Quiroga, Josep Antoni|||0000-0003-1622-0350, Reif, Andreas|||0000-0002-0992-634X, Reininghaus, Eva Z., Ribasés Haro, Marta|||0000-0003-1039-1116, Rietschel, Marcella|||0000-0002-5236-6149, Schall, Ulrich, Schofield, Peter R.|||0000-0003-2967-9662, Schulze, Thomas G., Scott, Laura J.|||0000-0002-4886-5084, Scott, Rodney J.|||0000-0001-7724-3404, Serretti, Alessandro, Smoller, Jordan W.|||0000-0002-0381-6334, Świątkowska, Beata, Soler Artigas, María|||0000-0002-3213-1107, Stein, Dan J.|||0000-0001-7218-7810, Streit, Fabian|||0000-0003-1080-4339, Toma, Claudio|||0000-0003-3901-7507, Tooney, Paul, Vawter, Marquis P., Vieta, Eduard|||0000-0002-0548-0053, Vincent, John B., Waldman, Irwin D.|||0000-0002-6862-1837, Weickert, Cynthia Shannon, Weickert, Thomas, Witt, Stephanie H.|||0000-0002-1571-1468, Hong, Kyung Sue, Ikeda, Masashi|||0000-0001-6237-2449, Iwata, Nakao|||0000-0003-3189-6076, Won, Hong Hee, Edenberg, Howard J.|||0000-0003-0344-9690, Ripke, Stephan|||0000-0003-3622-835X, Raj, Towfique|||0000-0002-9355-5704, Coleman, Jonathan R.I., Mullins, Niamh
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:dnet:uabarcelona_::45470e766b7a9a8d42c34bf162e777e3
Acceso en línea:https://ddd.uab.cat/record/326798
https://dx.doi.org/urn:doi:10.1038/s41593-025-01998-z
Access Level:acceso abierto
Palabra clave:Bipolar Disorder
Chromosome Mapping
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Multifactorial Inheritance
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Descripción
Sumario:Bipolar disorder is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 bipolar disorder risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci and prioritized 17 likely causal SNPs for bipolar disorder. We mapped these SNPs to genes and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci and results from rare variant exome sequencing in bipolar disorder. Convergent lines of evidence supported the roles of genes involved in neurotransmission and neurodevelopment, including SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, FKBP2, RASGRP1, FURIN, FES, MED24 and THRA among others in bipolar disorder. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance of bipolar disorder polygenic risk scores across diverse populations and present a high-throughput fine-mapping pipeline.

Similares en LA Referencia