Beyond Lancaster and York: Contextualizing Wars of the Roses Board Games in Scholarly Consensus

David DefriesThe English Wars of the Roses, fought from roughly 1455 to 1485 between the royal houses of Lancaster and York, have proven surprisingly popular among board game designers. In creating games that seek to demonstrate the infamous chaos of the wars, these games have also begun engaging with each other on a historical level—each new game attempts to build upon the achievements of the first by drawing closer and closer to the current scholarly consensus. Despite this unique feat of forming an academic debate through the medium of board games, however, no designer has yet fully reflected key elements of the scholarly consensus. For this reason, this paper lays out an original design, intended as a contribution to the ongoing discussion of how the wars should best be adapted into tabletop games. This paper describes the ways in which this new design constitutes an important addition to the set of Wars of the Roses board games, through incorporating both newer innovations in game design and recent scholarship. First, the template for this type of board game is traced back to the Avalon Hill title Kingmaker. It is then explained how additional games have diverged from Kingmaker’s model, but have not yet fully matched the current academic consensus regarding the motivations and timeframe of the war. Finally, the original design is explained, highlighting the ways in which this new game selectively breaks from Kingmaker’s precedent in order to better reflect these elements that scholars find key to explaining the wars

Large-scale exome-wide association analysis identifies loci for White Blood Cell Traits and Pleiotropy with Immune-Mediated Diseases

White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of ∼157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3 UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases