Additional common loci associated with stroke and obesity identified using pleiotropic analytical approach.

Stroke is a complex disease with multiple etiologies. Numerous studies suggest an established association between obesity and stroke, which may partly arise from the shared genetic components between the two phenotypes. Despite genome-wide association studies (GWASs) have identified some loci associated with stroke and obesity individually, the estimated genetic variability explained by these loci is limited (especially for stroke) and the pleiotropic loci between them are largely unknown. In this study, we jointly applied the pleiotropy-informed conditional false discovery rate (cFDR) method and the genetic analysis incorporating pleiotropy and annotation (GPA) method on summary statistics of two large GWASs to detect the genetic overlap between stroke (n = 446,696) and obesity (n = 681,275). Stratified Q-Q and fold-enrichment plots showed strong pleiotropic enrichment between the two phenotypes. With cFDR < 0.05 and fdr.GPA < 0.2, we identified 24 (16 novel) stroke-associated SNPs and 12 (10 novel) of them to be potentially pleiotropic SNPs for both phenotypes. The corresponding genes were enriched in trait-associated gene ontology (GO) terms "brain development" and "negative regulation of transport". In conclusion, our study demonstrated the feasibility and effectivity of the two pleiotropic methods which successfully improved the genetic discovery by incorporating related GWAS datasets and validated the genetic intercommunity between stroke and obesity. The identification of pleiotropic loci may provide us any new insights into potential genetic and etiology mechanism between them for the further studies.

40,585 European ancestry stroke cases, 406,111 European ancestry controls, 681,275 European ancestry individuals