Common Variants at 9p21 and 8q22 Are Associated with Increased Susceptibility to Optic Nerve Degeneration in Glaucoma

Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95%CI 0.63–0.75], p = 1.86×10−18), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95%CI 1.21–1.43], p = 3.87×10−11). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95% CI 0.50–0.67], p = 1.17×10−12) and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95% CI 0.53–0.72], p = 8.88×10−10). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95% CI 0.41–0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95% CI 0.54–1.06], p = 0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma

Different and diverse anaerobic microbiota were seen in women living with HIV with unsuppressed HIV viral load and in women with recurrent bacterial vaginosis: a cohort study

Objective: To compare the vaginal microbiota of women living with HIV (WLWH) with the vaginal microbiota of women with recurrent bacterial vaginosis (BV) and healthy women without HIV to determine if there are differences in the vaginal microbiome, what factors influence these differences, and to characterise HIV clinical parameters including viral load and CD4 count in relation to the vaginal microbiome. Design: Observational cohort study. Setting: Canada. Population: Women aged 18–49 years who were premenopausal and not pregnant were recruited into three cohorts: healthy women, WLWH and women with recurrent BV. Methods: Demographic and clinical data were collected via interviews and medical chart reviews. Vaginal swabs were collected for Gram-stain assessment and microbiome profiling using the cpn60 barcode sequence. Main outcome measures: To compare overall community composition differences, we used compositional data analysis methods, hierarchical clustering and Kruskal–Wallis tests where appropriate. Results: Clinical markers such as odour and abnormal discharge, but not irritation, were associated with higher microbial diversity. WLWH with unsuppressed HIV viral loads were more likely than other groups to have non-Gardnerella-dominated microbiomes. HIV was associated with higher vaginal microbial diversity and this was related to HIV viral load, with unsuppressed women demonstrating significantly higher relative abundance of Megasphaera genomosp. 1, Atopobium vaginae and Clostridiales sp. (all P \u3c 0.05) compared with all other groups. Conclusions: In WLWH, unsuppressed HIV viral loads were associated with a distinct dysbiotic profile consisting of very low levels of Lactobacillus and high levels of anaerobes. Tweetable abstract: Vaginal microbiomes in WLWH with viral load \u3e50 copies/ml have distinct dysbiotic profiles with high levels of anaerobes

Return Relationships between Listed Banks and Real Estate Firms: Evidence from Seven Asian Economies

This paper studies the return relationships between listed banks and real estate firms in seven Asian economies before and after the Asian financial crisis. We find that listed banks were exposed to real estate risk both before and after the crisis, but that the exposure increased in the post-crisis period. After the crisis, the hidden risk of real estate collateral in the bank lending process was explicit, as was evidenced by the increased sensitivity and the structure break. In terms of causality, the returns of listed real estate firms are found to Granger-cause the returns of listed banks. However, there is mixed evidence as to whether listed bank returns Granger-cause the returns of listed real estate firms. The study is significant because it indicates the importance of lending policies in relation to the real estate market in establishing a healthy financial system. Copyright Springer Science + Business Media, Inc. 2005real estate markets, mortgage lending, Asian financial crisis, banking systems, non-performing loans,