Open Access

Maria Koromina, Ashvin Ravi, Georgia Panagiotaropoulou, Brian M. Schilder, Jack Humphrey, Alice Braun, Tim Bidgeli, Chris Chatzinakos, Brandon Coombes, Jaeyoung Kim, Xiaoxi Liu, Chikashi Terao, Kevin S. O'Connell, Mark Adams, Rolf Adolfsson, Martin Alda, Lars Alfredsson, Till Andlauer, Ole A. Andreassen, Anastasia Antoniou, Bernhard T. Baune, Susanne Bengesser, Joanna Biernacka, Michael Boehnke, Rosa Bosch, Murray Cairns, Vaughan J. Carr, Miquel Casas Brugué, Stanley Catts, Sven Cichon, Aiden Corvin, Nicholas Craddock, Konstantinos Dafnas, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Arianna Di Florio, Dimitris Dikeos, Frederike Tabea Fellendorf, Panagiotis Ferentinos, Andreas Josef Forstner, Liz Forty, Mark Frye, Janice M. Fullerton, Micha Gawlik, Ian R. Gizer, Katherine Gordon-Smith, Melissa J. Green, Maria Grigoroiu-Serbanescu, José Guzman-Parra, Tim Hahn, Frans Henskens, Jan Hillert, Assen V. Jablensky, Lisa Jones, Ian Jones, Lina Jonsson, John R. Kelsoe, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Manolis Kogevinas, Mikael Landén, Marion Leboyer, Melanie Lenger, Jolanta Lissowska, Christine Lochner, Carmel Loughland, Donald MacIntyre, Nicholas G. Martin, Eirini Maratou, Carol A. Mathews, Fermı́n Mayoral, Susan L. McElroy, Nathaniel W. McGregor, Andrew M. McIntosh, Andrew McQuillin, Patricia Michie, Vihra Milanova, Philip B. Mitchell, Paraskevi Moutsatsou, Bryan Mowry, Bertram Müller-Myhsok, Richard M. Myers, Igor Nenadić, Markus Maria Nöthen, Claire O'Donovan, Michael O'Donovan, Roel André Ophoff, Michael J. Owen, Christos Pantelis, Carlos Pato, Michele T. Pato, George P. Patrinos, Joanna M. Pawlak, Roy H. Perlis, Evgenia Porichi, Danielle Posthuma, Josep Antoni Ramos-Quiroga, Andreas Reif, Eva Z. Reininghaus, Marta Ribasés, Marcella Rietschel, Ulrich Schall, Thomas Gerd Schulze, Laura J. Scott, Rodney J. Scott, Alessandro Serretti, Cynthia Shannon Weickert, Jordan W. Smoller, Marı́a Soler Artigas, Dan J. Stein, Fabian Streit, Claudio Toma, Paul Tooney, Eduard Vieta, John B. Vincent, Irwin D. Waldman, Thomas Weickert, Stephanie H. Witt, Kyung Sue Hong, Masashi Ikeda, Nakao Iwata, Beata Świątkowska, Hong-Hee Won, Howard J. Edenberg, Stephan Ripke, Towfique Raj, Jonathan R. I. Coleman, Niamh Mullins

• 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).