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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).
Sedimentary charcoal records are widely used to reconstruct regional changes in fire regimes through time in the geological past. Existing global compilations are not geographically comprehensive and do not provide consistent metadata for all sites. Furthermore, the age models provided for these records are not harmonised and many are based on older calibrations of the radiocarbon ages. These issues limit the use of existing compilations for research into past fire regimes. Here, we present an expanded database of charcoal records, accompanied by new age models based on recalibration of radiocarbon ages using IntCal20 and Bayesian age-modelling software. We document the structure and contents of the database, the construction of the age models, and the quality control measures applied. We also record the expansion of geographical coverage relative to previous charcoal compilations and the expansion of metadata that can be used to inform analyses. This first version of the Reading Palaeofire Database contains 1676 records (entities) from 1480 sites worldwide. The database (RPDv1b – Harrison et al., 2021) is available at https://doi.org/10.17864/1947.000345.
"Wir haben kein Wort, um Geist-Körper – beides im wechselseitigen Vollzug vereint – zu benennen." Diese Behauptung John Deweys über das fehlende Einheitswort klingt nach wie vor wahr, trotz der vielen Jahrzehnte, die seit ihrer Äußerung vergangen sind. Der Gelehrtengemeinschaft fehlt es an der Möglichkeit, den Körper so zu diskutieren, dass vermöge ein und derselben Konzeption dessen qualiagesättigte phänomenale Eigenschaften (d.h. die lebendige Erfahrung) und dessen kausalitätsrelevante physikalische Eigenschaften (d.h. der stofflich zusammengesetzte Körper) gemeinsam anerkannt würden. Natürlich sind sich viele Forscher dieser Situation bewusst und appellieren an die fragliche Einheit mittels Zwei-Wort-Wendungen wie etwa Deweys "Geist-Körper". In diesem Sinne spricht auch Richard Shusterman vom "empfindsamen Soma" ("sentient soma") und fügt folgenden Vorbehalt hinzu: "Soma" sei so zu verstehen, dass es "bereits Leben und ein bestimmtes Maß an zielorientiertem Empfindungsvermögen beinhaltet, womit Soma vom bloßen Körper (der sich in einem leb- und empfindungslosen Zustand befinden kann) unterscheidbar ist".