Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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Koromina, M; Ravi, A; Panagiotaropoulou, G; Schilder, BM; Humphrey, J; Braun, A; Bidgeli, T; Chatzinakos, C; Coombes, B; Kim, J; Liu, X; Terao, C; O, 'Connell, KS; Adams, M; Adolfsson, R; Alda, M; Alfredsson, L; Andlauer, TFM; Andreassen, OA; Antoniou, A; Baune, BT; Bengesser, S; Biernacka, J; Boehnke, M; Bosch, R; Cairns, M; Carr, VJ; Casas, M; Catts, S; Cichon, S; Corvin, A; Craddock, N; Dafnas, K; Dalkner, N; Dannlowski, U; Degenhardt, F; Di, Florio, A; Dikeos, D; Fellendorf, FT; Ferentinos, P; Forstner, AJ; Forty, L; Frye, M; Fullerton, JM; Gawlik, M; Gizer, IR; Gordon-Smith, K; Green, MJ; Grigoroiu-Serbanescu, M; Guzman-Parra, J; Hahn, T; Henskens, F; Hillert, J; Jablensky, AV; Jones, L; Jones, I; Jonsson, L; Kelsoe, JR; Kircher, T; Kirov, G; Kittel-Schneider, S; Kogevinas, M; Landén, M; Leboyer, M; Lenger, M; Lissowska, J; Lochner, C; Loughland, C; MacIntyre, D; Martin, NG; Maratou, E; Mathews, CA; Mayoral, F; McElroy, SL; McGregor, NW; McIntosh, A; McQuillin, A; Michie, P; Milanova, V; Mitchell, PB; Moutsatsou, P; Mowry, B; Müller-Myhsok, B; Myers, R; Nenadić, I; Nöthen, MM; O'Donovan, C; O'Donovan, M; Ophoff, RA; Owen, MJ; Pantelis, C; Pato, C; Pato, MT; Patrinos, GP; Pawlak, JM; Perlis, RH; Porichi, E; Posthuma, D; Ramos-Quiroga, JA; Reif, A; Reininghaus, EZ; Ribasés, M; Rietschel, M; Schall, U; Schulze, TG; Scott, L; Scott, RJ; Serretti, A; Weickert, CS; Smoller, JW; Artigas, MS; Stein, DJ; Streit, F; Toma, C; Tooney, P; Vieta, E; Vincent, JB; Waldman, ID; Weickert, T; Witt, SH; Hong, KS; Ikeda, M; Iwata, N; Świątkowska, B; Won, HH; Edenberg, HJ; Ripke, S; Raj, T; Coleman, JRI; Mullins, N.
Fine-mapping genomic loci refines bipolar disorder risk genes.
medRxiv. 2024;
Doi: 10.1101/2024.02.12.24302716
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- Autor*innen der Med Uni Graz:
- Bengesser Susanne
- Dalkner Nina
- Fellendorf Frederike
- Lenger Melanie
- Reininghaus Bernd
- Reininghaus Eva
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- 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).