Genome-wide Association Study Identifies SESTD1 as a Novel Risk Gene for Lithium Responsive Bipolar Disorder

Lithium is the mainstay prophylactic treatment for bipolar disorder (BD), but treatment response varies considerably across individuals. Patients who respond well to lithium treatment might represent a relatively homogeneous subtype of this genetically and phenotypically diverse disorder. Here, we performed genome-wide association studies (GWAS) to identify (i) specific genetic variations influencing lithium response and (ii) genetic variants associated with risk for lithium-responsive BD. Patients with BD and controls were recruited from Sweden and the United Kingdom. GWAS were performed on 2698 patients with subjectively defined (self-reported) lithium response and 1176 patients with objectively defined (clinically documented) lithium response. We next conducted GWAS comparing lithium responders with healthy controls (1639 subjective responders and 8899 controls; 323 objective responders and 6684 controls). Meta-analyses of Swedish and UK results revealed no significant associations with lithium response within the bipolar subjects. However, when comparing lithium-responsive patients with controls, two imputed markers attained genome-wide significant associations, among which one was validated in confirmatory genotyping (rs116323614, P=2.74 × 10-8). It is an intronic single-nucleotide polymorphism (SNP) on chromosome 2q31.2 in the gene SEC14 and spectrin domains 1 (SESTD1), which encodes a protein involved in regulation of phospholipids. Phospholipids have been strongly implicated as lithium treatment targets. Furthermore, we estimated the proportion of variance for lithium-responsive BD explained by common variants ('SNP heritability') as 0.25 and 0.29 using two definitions of lithium response. Our results revealed a genetic variant in SESTD1 associated with risk for lithium-responsive BD, suggesting that the understanding of BD etiology could be furthered by focusing on this subtype of BD.

Beyond the Acronyms: Sport Diplomacy and the Classification of the International Olympic Committee

Diplomacy often finds itself reduced to actions centred on states. However, after the Cold War, international relations and diplomacy have expanded with different actors growing into significant roles, particularly in the increase of diplomatic relations in the context of sport. The classification and significance of other actors remains under-researched in relation to sport, with literature focusing more on the growth of new and varying practices of diplomacy. This analysis contends that there is a need to interrogate fundamental components of modern diplomacy—with the actor being the focus—more specifically the classification of sports organisations in diplomacy. It is relevant as a more accurate understanding of sports organisations will contribute to how diplomatic studies can analyse and evaluate modern diplomacy within the context of sport. The International Olympic Committee is the actor used to illustrate how problematic classifications currently in the academic literature translate into weak and reduced analysis and evaluation of its role and significance in diplomacy. As counterpoint, this analysis proposes an analytical framework of socio-legal theory that harnesses legal regulation as a benchmark to classify an actor’s capacity within a society. In consequence, the IOC is as an active and significant contributor to the ever expanding and complex diplomatic environment and wider society.