University of Worcester Worcester Research and Publications
 
  USER PANEL:
  ABOUT THE COLLECTION:
  CONTACT DETAILS:

Fine-mapping genomic loci refines bipolar disorder risk genes

Koromina, M. ORCID: https://orcid.org/0000-0001-8843-082X, Ravi, A. ORCID: https://orcid.org/0009-0001-6225-7026, Panagiotaropoulou, G. ORCID: https://orcid.org/0000-0001-9516-6158, Schilder, B. ORCID: https://orcid.org/0000-0001-5949-2191, Humphrey, J. ORCID: https://orcid.org/0000-0002-6274-6620, Braun, A. ORCID: https://orcid.org/0000-0003-1145-0261, Bidgeli, T., Chatzinakos, C., Coombes, B. ORCID: https://orcid.org/0000-0003-4322-5923, Kim, J., Liu, X., Terao, C., O 'Connell, K. ORCID: https://orcid.org/0000-0002-6865-8795, Adams, M., Adolfsson, R. ORCID: https://orcid.org/0000-0001-9785-8473, Alda, M. ORCID: https://orcid.org/0000-0001-9544-3944, Alfredsson, L. ORCID: https://orcid.org/0000-0003-1688-6697, Andlauer, T. ORCID: https://orcid.org/0000-0002-2917-5889, Andreassen, O. ORCID: https://orcid.org/0000-0002-4461-3568, Antoniou, A. ORCID: https://orcid.org/0000-0001-9557-8793, Baune, B. ORCID: https://orcid.org/0000-0001-6548-426X, Bengesser, S. ORCID: https://orcid.org/0000-0001-8012-908X, Biernacka, J. ORCID: https://orcid.org/0000-0001-9350-4440, Boehnke, M. ORCID: https://orcid.org/0000-0002-6442-7754, Bosch, R. ORCID: https://orcid.org/0000-0002-7596-183X, Cairns, M. ORCID: https://orcid.org/0000-0003-2490-2538, Carr, V. ORCID: https://orcid.org/0000-0002-8907-5804, Casas, M., Catts, S., Cichon, S. ORCID: https://orcid.org/0000-0002-9475-086X, Corvin, A. ORCID: https://orcid.org/0000-0001-6717-4089, Craddock, N. ORCID: https://orcid.org/0000-0003-2171-0610, Dafnas, K. ORCID: https://orcid.org/0009-0009-1117-3816, Dalkner, N. ORCID: https://orcid.org/0000-0001-7716-3674, Dannlowski, U. ORCID: https://orcid.org/0000-0002-0623-3759, Degenhardt, F. ORCID: https://orcid.org/0000-0002-1685-8904, Di Florio, A. ORCID: https://orcid.org/0000-0003-0338-2748, Dikeos, D. ORCID: https://orcid.org/0000-0003-4217-5282, Fellendorf, F. ORCID: https://orcid.org/0000-0001-7215-3848, Ferentinos, P. ORCID: https://orcid.org/0000-0001-8531-5623, Forstner, A. ORCID: https://orcid.org/0000-0002-1876-6368, Forty, L. ORCID: https://orcid.org/0000-0002-4349-8414, Frye, M. ORCID: https://orcid.org/0000-0001-6997-4215, Fullerton, J. ORCID: https://orcid.org/0000-0003-4014-4490, Gawlik, M. ORCID: https://orcid.org/0000-0002-2166-3992, Gizer, I. ORCID: https://orcid.org/0000-0002-4026-5674, Gordon-Smith, Katherine ORCID: https://orcid.org/0000-0003-4083-1143, Green, M., Grigoroiu-Serbanescu, M. ORCID: https://orcid.org/0000-0002-1304-6687, Guzman-Parra, J. ORCID: https://orcid.org/0000-0002-1463-6435, Hahn, T., Henskens, F. ORCID: https://orcid.org/0000-0003-2358-5630, Hillert, J., Jablensky, A., Jones, Lisa ORCID: https://orcid.org/0000-0002-5122-8334, Jones, I. ORCID: https://orcid.org/0000-0001-5821-5889, Jonsson, L. ORCID: https://orcid.org/0000-0002-3175-103X, Kelsoe, J. ORCID: https://orcid.org/0000-0002-3013-2333, Kircher, T. ORCID: https://orcid.org/0000-0002-2514-2625, Kirov, G. ORCID: https://orcid.org/0000-0002-3427-3950, Kittel-Schneider, S. ORCID: https://orcid.org/0000-0003-3057-6150, Kogevinas, M. ORCID: https://orcid.org/0000-0002-9605-0461, Landén, M. ORCID: https://orcid.org/0000-0002-4496-6451, Leboyer, M. ORCID: https://orcid.org/0000-0001-5473-3697, Lenger, M., Lissowska, J. ORCID: https://orcid.org/0000-0003-2695-5799, Lochner, C. ORCID: https://orcid.org/0000-0002-4766-3704, Loughland, C., MacIntyre, D., Martin, N., Maratou, E. ORCID: https://orcid.org/0000-0002-9982-7942, Mathews, C. ORCID: https://orcid.org/0000-0003-2208-7058, Mayoral, F. ORCID: https://orcid.org/0000-0002-9710-9672, McElroy, S. ORCID: https://orcid.org/0000-0002-8879-0865, McGregor, N. ORCID: https://orcid.org/0000-0001-7195-4993, McIntosh, A. ORCID: https://orcid.org/0000-0002-0198-4588, McQuillin, A. ORCID: https://orcid.org/0000-0003-1567-2240, Michie, P., Milanova, V., Mitchell, P., Moutsatsou, P. ORCID: https://orcid.org/0000-0001-9549-2295, Mowry, B., Müller-Myhsok, B., Myers, R. ORCID: https://orcid.org/0000-0001-9701-676X, Nenadić, I., Nöthen, M. ORCID: https://orcid.org/0000-0002-8770-2464, O'Donovan, C. ORCID: https://orcid.org/0000-0002-8640-3016, O'Donovan, M., Ophoff, R. ORCID: https://orcid.org/0000-0002-8287-6457, Owen, M. ORCID: https://orcid.org/0000-0003-4798-0862, Pantelis, C. ORCID: https://orcid.org/0000-0002-9565-0238, Pato, C., Pato, M. ORCID: https://orcid.org/0000-0002-4589-7398, Patrinos, G. ORCID: https://orcid.org/0000-0002-0519-7776, Pawlak, J. ORCID: https://orcid.org/0000-0001-5064-3707, Perlis, R. ORCID: https://orcid.org/0000-0002-5862-6757, Porichi, E., Posthuma, D. ORCID: https://orcid.org/0000-0001-7582-2365, Ramos-Quiroga, J., Reif, A. ORCID: https://orcid.org/0000-0002-0992-634X, Reininghaus, E. ORCID: https://orcid.org/0000-0001-5964-4087, Ribasés, M. ORCID: https://orcid.org/0000-0003-1039-1116, Rietschel, M. ORCID: https://orcid.org/0000-0002-5236-6149, Schall, U., Schulze, T. ORCID: https://orcid.org/0000-0001-6624-2975, Scott, L., Scott, R. ORCID: https://orcid.org/0000-0001-7724-3404, Serretti, A. ORCID: https://orcid.org/0000-0003-4363-3759, Weickert, C., Smoller, J. ORCID: https://orcid.org/0000-0002-0381-6334, Artigas, M. ORCID: https://orcid.org/0000-0002-3213-1107, Stein, D. ORCID: https://orcid.org/0000-0001-7218-7810, Streit, F. ORCID: https://orcid.org/0000-0003-1080-4339, Toma, C., Tooney, P., Vieta, E. ORCID: https://orcid.org/0000-0002-0548-0053, Vincent, J. ORCID: https://orcid.org/0000-0003-0692-2519, Waldman, I. ORCID: https://orcid.org/0000-0002-6862-1837, Weickert, T., Witt, S. ORCID: https://orcid.org/0000-0002-1571-1468, Hong, K. ORCID: https://orcid.org/0000-0001-6237-2449, Ikeda, M. ORCID: https://orcid.org/0000-0003-3189-6076, Iwata, N., Świątkowska, B., Won, H. ORCID: https://orcid.org/0000-0001-5719-0552, Edenberg, H. ORCID: https://orcid.org/0000-0003-0344-9690, Ripke, S. ORCID: https://orcid.org/0000-0003-3622-835X, Raj, T. ORCID: https://orcid.org/0000-0002-9355-5704, Coleman, J. ORCID: https://orcid.org/0000-0002-6759-0944 and Mullins, N. ORCID: https://orcid.org/0000-0001-8021-839X (2024) Fine-mapping genomic loci refines bipolar disorder risk genes. medRxiv. pp. 1-34.

[thumbnail of Pre-Print]
Preview
Text (Pre-Print)
KGS.pdf - Other
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (1MB) | Preview

Abstract

Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD 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 22 likely causal SNPs for BD. 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 BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. 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 and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).

Item Type: Article
Additional Information:

This article is a preprint and has not been peer-reviewed. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

Divisions: College of Health, Life and Environmental Sciences > School of Allied Health and Community
Related URLs:
Copyright Info: The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
SWORD Depositor: Prof. Pub Router
Depositing User: Katherine Gordon-Smith
Date Deposited: 19 Apr 2024 14:23
Last Modified: 16 May 2024 14:36
URI: https://worc-9.eprints-hosting.org/id/eprint/13706

Actions (login required)

View Item View Item
 
     
Worcester Research and Publications is powered by EPrints 3 which is developed by the School of Electronics and Computer Science at the University of Southampton. More information and software credits.