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.

The Working Group on Scottish Sport and the Scottish Independence Referendum: an Unrealised Political 'Imaginary'?

In September 2014, a historic referendum on the issue of Scottish independence was held, with the potential to dissolve the political union between Scotland and the other constituent nations of the United Kingdom which had survived intact since the 1707 Act of Union. On a significantly high electoral turnout of 84.6%, the Scottish electorate opted to reject the proposals of the governing party in the devolved Scottish Parliament, the pro-independence Scottish National Party (SNP), to create an independent Scottish state, with 55.3% of the electorate voting ‘No’ to Scottish independence against a 44.7% ‘Yes’ vote. In the grand scheme of the Scottish independence referendum campaigns, sports policy remained a somewhat peripheral issue within the arguments forwarded by the Yes Scotland and Better Together campaigns. Nonetheless, developments such as the formation of the 'Sport for Yes' campaign sub-group, the inclusion of sport within the Scottish Government’s White Paper on Scottish independence and the establishment of the Working Group on Scottish Sport demonstrated that the potential implications of independence were still deemed significant enough to merit a degree of policy planning by the Scottish Government (Lafferty, 2014; Scottish Government, 2013; Working Group on Scottish Sport, 2013, 2014). This paper will critically consider the implications of the 'No' vote in the Scottish independence referendum for the latter of these developments, the policy proposals of the Working Group for Scottish Sport. Drawing upon the principles of critical discourse analysis, specifically the analytical framework proposed by Fairclough and Fairclough (2012), the content of this group's proposal will be examined in order to critically explore the policy for Scottish sport it envisaged for an independent Scottish state. The paper will then conclude by reflecting upon the extent to which elements of this political 'imaginary' (Fairclough and Fairclough, 2012) of Scottish sport remain a possibility for future sports policy in Scotland following the eventual 'No' vote in the referendum.