ObjectiveSystemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.MethodsWe newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations.ResultsWe identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10−8). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (rg=−0.242) and non-albumin protein (rg=0.238).ConclusionThis study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.

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The perfect hemostatic material should be capable of rapidly controlling substantial hemorrhaging from visceral organs, veins, and arteries. Ideally, it should be biodegradable, biocompatible, easily applied, and inexpensive. Herein, taking advantages of sodium alginate (SA), carboxymethyl chitosan (CMC), and collagen, a degradable powdery hemostatic composite (SACC) was synthesized using emulsification and cross-linking technology. The morphology and structure of SACC were determined using Fourier transform infrared spectroscopy and scanning electron microscopy (SEM). This hemostatic material exhibited a typical generic sphere shape with narrow size distribution, rough surface, and satisfactory water absorption. Using in vitro bleeding and in vivo bleeding models (rat liver injury model and rat tail amputation model), it was shown that SACC had superior hemostatic actions compared to CMC and SA. Excellent cytocompatibility was proven during cytotoxicity tests and SEM observations. Histomorphological evaluation during the wound healing process proved the superior biocompatibility of SACC in a rat liver injury model. Biodegradability of SACC was demonstrated by immunofluorescence techniques both in vitro and in vivo. In summary, we have demonstrated the enormous potential of SACC, which has excellent hemostatic activity, biodegradability, and biocompatibility properties for use in clinical hemostasis applications.

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