Dieses Ergebnis aus BASE kann Gästen nicht angezeigt werden. Login für vollen Zugriff.

Fine-mapping genomic loci refines bipolar disorder risk genes

Title:	Fine-mapping genomic loci refines bipolar disorder risk genes
Authors:	Koromina, M.; Ravi, A.; Panagiotaropoulou, G.; Schilder, B.; Humphrey, J.; Braun, A.; Bidgeli, T.; Chatzinakos, C.; Coombes, B.; Kim, J.; Liu, X.; Terao, C.; O 'Connell, K.; Adams, M.; Adolfsson, R.; Alda, M.; Alfredsson, L.; Andlauer, T.; Andreassen, O.; Antoniou, A.; Baune, B.; Bengesser, S.; Biernacka, J.; Boehnke, M.; Bosch, R.; Cairns, M.; Carr, V.; Casas, M.; Catts, S.; Cichon, S.; Corvin, A.; Craddock, N.; Dafnas, K.; Dalkner, N.; Dannlowski, U.; Degenhardt, F.; Di Florio, A.; Dikeos, D.; Fellendorf, F.; Ferentinos, P.; Forstner, A.; Forty, L.; Frye, M.; Fullerton, J.; Gawlik, M.; Gizer, I.; Gordon-Smith, Katherine; Green, M.; Grigoroiu-Serbanescu, M.; Guzman-Parra, J.; Hahn, T.; Henskens, F.; Hillert, J.; Jablensky, A.; Jones, Lisa; Jones, I.; Jonsson, L.; Kelsoe, J.; Kircher, T.; Kirov, G.; Kittel-Schneider, S.; Kogevinas, M.; Landén, M.; Leboyer, M.; Lenger, M.; Lissowska, J.; Lochner, C.; Loughland, C.; MacIntyre, D.; Martin, N.; Maratou, E.; Mathews, C.; Mayoral, F.; McElroy, S.; McGregor, N.; McIntosh, A.; McQuillin, A.; Michie, P.; Milanova, V.; Mitchell, P.; Moutsatsou, P.; Mowry, B.; Müller-Myhsok, B.; Myers, R.; Nenadić, I.; Nöthen, M.; O'Donovan, C.; O'Donovan, M.; Ophoff, R.; Owen, M.; Pantelis, C.; Pato, C.; Pato, M.; Patrinos, G.; Pawlak, J.; Perlis, R.; Porichi, E.; Posthuma, D.; Ramos-Quiroga, J.; Reif, A.; Reininghaus, E.; Ribasés, M.; Rietschel, M.; Schall, U.; Schulze, T.; Scott, L.; Scott, R.; Serretti, A.; Weickert, C.; Smoller, J.; Artigas, M.; Stein, D.; Streit, F.; Toma, C.; Tooney, P.; Vieta, E.; Vincent, J.; Waldman, I.; Weickert, T.; Witt, S.; Hong, K.; Ikeda, M.; Iwata, N.; Świątkowska, B.; Won, H.; Edenberg, H.; Ripke, S.; Raj, T.; Coleman, J.; Mullins, N.
Publisher Information:	Nature Publishing Group
Publication Year:	2025
Collection:	University of Worcester: Worcester Research and Publications
Description:	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.
Document Type:	article in journal/newspaper
File Description:	text
Language:	English
ISSN:	1097-6256
Relation:	https://eprints.worc.ac.uk/13706/1/KGS.pdf; https://eprints.worc.ac.uk/13706/7/fine%20mapping.pdf; Koromina, M. ORCID logoorcid:0000-0001-8843-082X , Ravi, A. ORCID logoorcid:0009-0001-6225-7026 , Panagiotaropoulou, G. ORCID logoorcid:0000-0001-9516-6158 , Schilder, B. ORCID logoorcid:0000-0001-5949-2191 , Humphrey, J. ORCID logoorcid:0000-0002-6274-6620 , Braun, A. ORCID logoorcid:0000-0003-1145-0261 , Bidgeli, T., Chatzinakos, C., Coombes, B. ORCID logoorcid:0000-0003-4322-5923 , Kim, J., Liu, X., Terao, C., O 'Connell, K. ORCID logoorcid:0000-0002-6865-8795 , Adams, M., Adolfsson, R. ORCID logoorcid:0000-0001-9785-8473 , Alda, M. ORCID logoorcid:0000-0001-9544-3944 , Alfredsson, L. ORCID logoorcid:0000-0003-1688-6697 , Andlauer, T. ORCID logoorcid:0000-0002-2917-5889 , Andreassen, O. ORCID logoorcid:0000-0002-4461-3568 , Antoniou, A. ORCID logoorcid:0000-0001-9557-8793 , Baune, B. ORCID logoorcid:0000-0001-6548-426X , Bengesser, S. ORCID logoorcid:0000-0001-8012-908X , Biernacka, J. ORCID logoorcid:0000-0001-9350-4440 , Boehnke, M. ORCID logoorcid:0000-0002-6442-7754 , Bosch, R. ORCID logoorcid:0000-0002-7596-183X , Cairns, M. ORCID logoorcid:0000-0003-2490-2538 , Carr, V. ORCID logoorcid:0000-0002-8907-5804 , Casas, M., Catts, S., Cichon, S. ORCID logoorcid:0000-0002-9475-086X , Corvin, A. ORCID logoorcid:0000-0001-6717-4089 , Craddock, N. ORCID logoorcid:0000-0003-2171-0610 , Dafnas, K. ORCID logoorcid:0009-0009-1117-3816 , Dalkner, N. ORCID logoorcid:0000-0001-7716-3674 , Dannlowski, U. ORCID logoorcid:0000-0002-0623-3759 , Degenhardt, F. ORCID logoorcid:0000-0002-1685-8904 , Di Florio, A. ORCID logoorcid:0000-0003-0338-2748 , Dikeos, D. ORCID logoorcid:0000-0003-4217-5282 , Fellendorf, F. ORCID logoorcid:0000-0001-7215-3848 , Ferentinos, P. ORCID logoorcid:0000-0001-8531-5623 , Forstner, A. ORCID logoorcid:0000-0002-1876-6368 , Forty, L. ORCID logoorcid:0000-0002-4349-8414 , Frye, M. ORCID logoorcid:0000-0001-6997-4215 , Fullerton, J. ORCID logoorcid:0000-0003-4014-4490 , Gawlik, M. ORCID logoorcid:0000-0002-2166-3992 , Gizer, I. ORCID logoorcid:0000-0002-4026-5674 , Gordon-Smith, Katherine ORCID logoorcid:0000-0003-4083-1143 , Green, M., Grigoroiu-Serbanescu, M. ORCID logoorcid:0000-0002-1304-6687 , Guzman-Parra, J. ORCID logoorcid:0000-0002-1463-6435 , Hahn, T., Henskens, F. ORCID logoorcid:0000-0003-2358-5630 , Hillert, J., Jablensky, A., Jones, Lisa ORCID logoorcid:0000-0002-5122-8334 , Jones, I. ORCID logoorcid:0000-0001-5821-5889 , Jonsson, L. ORCID logoorcid:0000-0002-3175-103X , Kelsoe, J. ORCID logoorcid:0000-0002-3013-2333 , Kircher, T. ORCID logoorcid:0000-0002-2514-2625 , Kirov, G. ORCID logoorcid:0000-0002-3427-3950 , Kittel-Schneider, S. ORCID logoorcid:0000-0003-3057-6150 , Kogevinas, M. ORCID logoorcid:0000-0002-9605-0461 , Landén, M. ORCID logoorcid:0000-0002-4496-6451 , Leboyer, M. ORCID logoorcid:0000-0001-5473-3697 , Lenger, M., Lissowska, J. ORCID logoorcid:0000-0003-2695-5799 , Lochner, C. ORCID logoorcid:0000-0002-4766-3704 , Loughland, C., MacIntyre, D., Martin, N., Maratou, E. ORCID logoorcid:0000-0002-9982-7942 , Mathews, C. ORCID logoorcid:0000-0003-2208-7058 , Mayoral, F. ORCID logoorcid:0000-0002-9710-9672 , McElroy, S. ORCID logoorcid:0000-0002-8879-0865 , McGregor, N. ORCID logoorcid:0000-0001-7195-4993 , McIntosh, A. ORCID logoorcid:0000-0002-0198-4588 , McQuillin, A. ORCID logoorcid:0000-0003-1567-2240 , Michie, P., Milanova, V., Mitchell, P., Moutsatsou, P. ORCID logoorcid:0000-0001-9549-2295 , Mowry, B., Müller-Myhsok, B., Myers, R. ORCID logoorcid:0000-0001-9701-676X , Nenadić, I., Nöthen, M. ORCID logoorcid:0000-0002-8770-2464 , O'Donovan, C. ORCID logoorcid:0000-0002-8640-3016 , O'Donovan, M., Ophoff, R. ORCID logoorcid:0000-0002-8287-6457 , Owen, M. ORCID logoorcid:0000-0003-4798-0862 , Pantelis, C. ORCID logoorcid:0000-0002-9565-0238 , Pato, C., Pato, M. ORCID logoorcid:0000-0002-4589-7398 , Patrinos, G. ORCID logoorcid:0000-0002-0519-7776 , Pawlak, J. ORCID logoorcid:0000-0001-5064-3707 , Perlis, R. ORCID logoorcid:0000-0002-5862-6757 , Porichi, E., Posthuma, D. ORCID logoorcid:0000-0001-7582-2365 , Ramos-Quiroga, J., Reif, A. ORCID logoorcid:0000-0002-0992-634X , Reininghaus, E. ORCID logoorcid:0000-0001-5964-4087 , Ribasés, M. ORCID logoorcid:0000-0003-1039-1116 , Rietschel, M. ORCID logoorcid:0000-0002-5236-6149 , Schall, U., Schulze, T. ORCID logoorcid:0000-0001-6624-2975 , Scott, L., Scott, R. ORCID logoorcid:0000-0001-7724-3404 , Serretti, A. ORCID logoorcid:0000-0003-4363-3759 , Weickert, C., Smoller, J. ORCID logoorcid:0000-0002-0381-6334 , Artigas, M. ORCID logoorcid:0000-0002-3213-1107 , Stein, D. ORCID logoorcid:0000-0001-7218-7810 , Streit, F. ORCID logoorcid:0000-0003-1080-4339 , Toma, C., Tooney, P., Vieta, E. ORCID logoorcid:0000-0002-0548-0053 , Vincent, J. ORCID logoorcid:0000-0003-0692-2519 , Waldman, I. ORCID logoorcid:0000-0002-6862-1837 , Weickert, T., Witt, S. ORCID logoorcid:0000-0002-1571-1468 , Hong, K. ORCID logoorcid:0000-0001-6237-2449 , Ikeda, M. ORCID logoorcid:0000-0003-3189-6076 , Iwata, N., Świątkowska, B., Won, H. ORCID logoorcid:0000-0001-5719-0552 , Edenberg, H. ORCID logoorcid:0000-0003-0344-9690 , Ripke, S. ORCID logoorcid:0000-0003-3622-835X , Raj, T. ORCID logoorcid:0000-0002-9355-5704 , Coleman, J. ORCID logoorcid:0000-0002-6759-0944 and Mullins, N. ORCID logoorcid:0000-0001-8021-839X (2025) Fine-mapping genomic loci refines bipolar disorder risk genes. Nature Neuroscience, 28. pp. 1393-1411. ISSN Print: 1097-6256 Online:1546-1726
Availability:	https://eprints.worc.ac.uk/13706/; https://eprints.worc.ac.uk/13706/1/KGS.pdf; https://eprints.worc.ac.uk/13706/7/fine%20mapping.pdf; https://www.nature.com/articles/s41593-025-01998-z
Rights:	cc_by_nc_nd_4
Accession Number:	edsbas.877347E
Database:	BASE