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Background: Recent studies found associations between non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS), but the causal nature of this association is still uncertain. Methods: We performed a bidirectional two-sample Mendelian randomization (MR) analysis to test for the causal association between NAFLD and PCOS using data from a large-scale biopsy-confirmed NAFLD genome-wide association study (GWAS) (1483 cases and 17,781 controls) and PCOS GWAS (10,074 cases and 103,164 controls) in European ancestries. Data from glycemic-related traits GWAS (in up to 200,622 individuals) and sex hormones GWAS (in 189,473 women) in the UK Biobank (UKB) were used in the MR mediation analysis to assess potential mediating roles of these molecules in the causal pathway between NAFLD and PCOS. Replication analysis was conducted using two independent datasets from NAFLD and PCOS GWASs in the UKB and a meta-analysis of data from FinnGen and the Estonian Biobank, respectively. A linkage disequilibrium score regression was conducted to assess genetic correlations between NAFLD, PCOS, glycemic-related traits, and sex hormones using full summary statistics. Results: Individuals with higher genetic liability to NAFLD were more likely to develop PCOS (OR per one-unit log odds increase in NAFLD: 1.10, 95% CI: 1.02–1.18; P = 0.013). Indirect causal effects of NAFLD on PCOS via fasting insulin only (OR: 1.02, 95% CI: 1.01–1.03; P = 0.004) and further a suggestive indirect causal effect via fasting insulin in concert with androgen levels were revealed in MR mediation analyses. However, the conditional F statistics of NAFLD and fasting insulin were less than 10, suggesting likely weak instrument bias in the MVMR and MR mediation analyses. Conclusions: Our study suggests that genetically predicted NAFLD was associated with a higher risk of developing PCOS but less evidence for vice versa. Fasting insulin and sex hormones might mediate the link between NAFLD and PCOS. [ABSTRACT FROM AUTHOR]

Mandatory inclusionary housing, which requires private developers to include a portion of affordable housing units in market-rate developments, has become an internationally popular policy instrument to recapture land value and create affordable housing. Two common criticisms of mandatory inclusionary housing are that 1) it produces limited affordable housing and 2) it constrains housing supply and pushes up housing prices. In this study we examined how private developers responded to an expansion of a strong mandatory inclusionary housing scheme in London (UK). Between 2005 and 2008, each of the 33 local authorities in Greater London extended their affordable housing requirements, previously for housing projects with 15 or more units, to those with 10 to 14 units. We found that the expansion led to a reduction in new developments in the target market segment (projects with 10 to 14 units) and an increase in new developments in the unregulated alternative market segment (projects with 9 or fewer units). There was no net loss of new homes, though the strategic behavior of private developers could have dampened the affordable housing output of the expansion of mandatory inclusionary housing. Our findings suggest that, given appealing unregulated alternatives with low barriers, developers tend to divert development to avoid mandatory inclusionary housing. This, overall, calls for better evaluation of the potential alternatives and a more comprehensive, regional approach to inclusionary housing to maximize its effectiveness and to minimize its impacts on housing supply. [ABSTRACT FROM AUTHOR]

This study examines the total factor productivity (TFP) change of the UK airport industry from 2001 to 2009 using a Hicks-Moorsteen index method. The results show that the industry experienced an average annual growth in TFP of 0.32 per cent with efficiency change being the main contributor to the TFP growth. We find that private UK airports enjoy slightly higher TFP growth than those in public or mixed ownership. Regulation and airport size are found to have statistically significant effects on the airport productivity level. [ABSTRACT FROM AUTHOR]

Minimum parking standards, which require developers to build a certain amount of off-street parking spaces, are increasingly criticized for leading to excess parking supply and automobile travel in recent years. However, due to the difficulty in identifying the policy effect, few empirical studies have directly and accurately estimated the effects of parking standards on parking supply. The present study examines a parking reform in London, UK, where minimum parking standards for residential developments were replaced with maximum standards in the early 2000s. Using planning application records, we match neighboring pre-reform and post-reform developments to estimate the effect of the parking standard switch and further identify the “binding” and “capping” effects of minimum and maximum parking standards. It is found that the parking reform in London has led to a reduction of approximately 0.76 parking spaces per unit in residential development applications, or 49% of the pre-reform level. Minimum parking standards seem to have a larger impact than maximum ones on parking supply that fell more upon inner city developments, while maximum parking standards have more influenced suburban neighborhoods. Market forces have played a major role in the decline of parking supply. The findings provide strong evidence for the market distortion effect of minimum parking standards. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the associations between courses of depression, the application of depression treatment, and the risk of incident dementia. In this prospective cohort study, 354,313 participants ages 50–70 years were recruited from the UK Biobank between 2006 and 2010 and were followed until 2020, with a total of 4,212,929 person-years. We initially studied the effect of depression on dementia incidence across 4 subgroups characterized by courses of depressive symptoms. Then, 46,820 participants with a diagnosis of depression were further categorized into treated and untreated groups. We compared the risk of dementia among different depression treatment groups in all participants who were depressed as well as 4 courses of depressive symptoms by performing survival analyses. Depression was associated with a 51% higher risk of dementia, among which the increasing, chronically high, and chronically low courses were associated with increased dementia risk, while no association was found in the decreasing course. Compared to those who were depressed but untreated, receiving depression treatments corresponded to a hazard ratio of 0.7 (95% CI, 0.62–0.77). Among the 3 detrimental courses, treatments for increasing and chronically low symptoms of depression were associated with a 32% and 28% lower risk of dementia, respectively, while the reduction effect for chronically high symptoms was insignificant. The negative association between depression treatment and incident dementia was significant in the increasing and chronically low courses, highlighting the necessity of timely interventional strategies before depression progresses to a chronically severe state. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the associations between maternal smoking (MS) and education score in adult offspring., Methods: To better understand this link, we performed a two-stage genome-wide by environment interaction studies (GWEIS) of MS and offspring education score in UK Biobank cohort. Specifically, 276 996 subjects from England were enrolled in the discovery study, while 24 355 subjects from Scotland and 14 526 subjects from Wales were enrolled in the replication study. GWEIS were conducted by PLINK 2.0 with MS used as an environmental risk factor., Results: Significant GWEIS associations ( P  < 0.0001) between MS and offspring education score in both the discovery cohort and two replicate cohorts (Scotland population and Wales population) were identified. GWEIS identified 2 independent significant single nucleotide polymorphism-MS interaction, with one variant located in the chromosomal 16 (rs72768988, Position: 22,768,798, P  = 1.22 × 10 -8 , β = 6.7662) and the other one located in 2q32.3 region (2 : 196424612&#95;GT&#95;G, Position: 196 424 612, 3.60 × 10 -9 , β = -0.4721)., Conclusion: Our results suggested 2q32.3 region and HECW2 gene could negatively moderate the influence of MS on offspring's educational status., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Asthma, one of the most common chronic respiratory disorders, is associated with the hyper-activation of the T-cell subset of adaptive immunity. The gut microbiota may be involved in the development of asthma through the production of short-chain fatty acids (SCFAs), exhibiting modulatory effects on Th. So, we performed a metagenome-wide association study (MWAS) of the fecal microbiota from individuals with asthma and healthy controls. And that was the first case to resolve the relationship between asthma and microbiome among UK adults., Results: The microbiota of the individuals with asthma consisted of fewer microbial entities than the microbiota of healthy individuals. Faecalibacterium prausnitzii, Sutterella wadsworthensis and Bacteroides stercoris were depleted in cases, whereas Clostridiums with Eggerthella lenta were over-represented in individuals with asthma. Functional analysis shows that the SCFAs might be altered in the microbiota of asthma patients., Conclusion: In all, the adult human gut microbiome of asthma patients is clearly different from healthy controls. The functional and taxa results showed that the change of asthma patients might related to SCFAs.