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.

In patients with developmental dysplasia of the hip, acetabular retroversion results from relatively deficient coverage by the posterior portion of the acetabulum. Developmental dysplasia with acetabular retroversion is associated with an earlier onset of pain than is developmental dysplasia with anteversion, suggesting a correlation between deficiency of the posterior acetabular wall and the earlier onset of pain.

Objective. To investigate the effects of combination treatment with an anticoagulant (warfarin) plus a lipid-lowering agent (probucol) on the prevention of steroid-induced osteonecrosis (ON) in rabbits.Methods. Adult male Japanese white rabbits were injected once intramuscularly with 20 mg/kg of methylprednisolone acetate into the right gluteus medius muscle. The rabbits were then divided into 4 groups and treated as follows: one group received warfarin plus probucol (WP; n ‫؍‬ 25), one received probucol alone (PA; n ‫؍‬ 30), one received warfarin alone (WA; n ‫؍‬ 26), and one received no treatment (nonprophylactic [NP]; n ‫؍‬ 20). Two weeks after the steroid injection, the femora and humeri were examined histopathologically for the presence of ON. The sizes of the bone marrow fat cells were examined morphologically. Hematologic examinations were performed before and after the steroid injection.Results. The incidence of ON in the WP group (5%) was significantly lower than that observed in the NP group (70%). While the incidence rates of ON in the PA (38%) and WA (33%) groups were also significantly lower than that in the NP group, they were significantly higher than that observed in the WP group. The sizes of the bone marrow fat cells in both the WP (53.5 ؎ 4.1 m) and the PA (52.0 ؎ 5.0 m) groups were significantly smaller than those in the NP group (60.0 ؎ 4.0 m). We also observed a prolongation of the prothrombin time and a reduction in the plasma lipid levels in the WP group during the study.Conclusion. This study experimentally confirmed that the combined use of an anticoagulant and a lipidlowering agent helps prevent steroid-induced ON in rabbits.

Although the manual placement of the cup resulted in 27% of outliers from the intended CA, the CA technique significantly reduced the dislocation after primary THA.

The results of the present study suggest that the shape of the low-intensity band on MRI is useful for the differentiating subchondral insufficiency fracture from osteonecrosis. In addition, among osteoporotic elderly women without any history of corticosteroid intake or alcohol abuse, a diagnosis of subchondral insufficiency fracture should be considered.