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Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a considerable health risk. Nevertheless, its risk factors are not thoroughly comprehended, and the association between the reticulocyte count and MASLD remains uncertain. This study aimed to explore the relationship between reticulocyte count and MASLD. Methods: A total of 310,091 individuals from the UK Biobank were included in this cross-sectional study, and 7,316 individuals were included in this prospective study. The cross-sectional analysis categorized reticulocyte count into quartiles, considering the sample distribution. Logistic regression models examined the connection between reticulocyte count and MASLD. In the prospective analysis, Cox analysis was utilized to investigate the association. Results: Our study findings indicate a significant association between higher reticulocyte count and an elevated risk of MASLD in both the cross-sectional and prospective analyses. In the cross-sectional analysis, the adjusted odds ratios (ORs) of MASLD increased stepwise over reticulocyte count quartiles (quartile 2:OR 1.22, 95% CI 1.17-1.28, p < 0.001; quartile 3: OR 1.44; 95% CI 1.38-1.51, p < 0.001; quartile 4: OR 1.66, 95% CI 1.59-1.74, p < 0.001). The results of prospective analyses were similar. Conclusion: Increased reticulocyte count was independently associated with a higher risk of MASLD. This discovery offers new insights into the potential of reticulocytes as biomarkers for MASLD. [ABSTRACT FROM AUTHOR]

Background Depression is a debilitating mental disorder that often coexists with anxiety. The genetic mechanisms of depression and anxiety have considerable overlap, and studying depression in non-anxiety samples could help to discover novel gene. We assess the genetic variation of depression in non-anxiety samples, using genome-wide association studies (GWAS) and linkage disequilibrium score regression (LDSC). Methods The GWAS of depression score and self-reported depression were conducted using the UK Biobank samples, comprising 99,178 non-anxiety participants with anxiety score <5 and 86,503 non-anxiety participants without self-reported anxiety, respectively. Replication analysis was then performed using two large-scale GWAS summary data of depression from Psychiatric Genomics Consortium (PGC). LDSC was finally used to evaluate genetic correlations with 855 health-related traits based on the primary GWAS. Results Two genome-wide significant loci for non-anxiety depression were identified: rs139702470 (p = 1.54 × 10−8, OR = 0.29) locate in PIEZO2, and rs6046722 (p = 2.52 × 10−8, OR = 1.09) locate in CFAP61. These associated genes were replicated in two GWAS of depression from PGC, such as rs1040582 (preplication GWAS1 = 0.02, preplication GWAS2 = 2.71 × 10−3) in CFAP61, and rs11661122 (preplication GWAS1 = 8.16 × 10−3, preplication GWAS2 = 8.08 × 10−3) in PIEZO2. LDSC identified 19 traits genetically associated with non-anxiety depression (p < 0.001), such as marital separation/divorce (rg = 0.45, SE = 0.15). Conclusions Our findings provide novel clues for understanding of the complex genetic architecture of depression. [ABSTRACT FROM AUTHOR]

This paper employs unique data on export transactions and corporate tax returns of UK multinational firms and finds that firms manipulate their transfer prices to shift profits to lower-taxed destinations. It shows that the 2009 tax reform in the United Kingdom, which changed the taxation of corporate profits from aworldwide to a territorial system, led to a substantial increase in transfer mispricing. It also provides evidence for a trade creation effect of transfer mispricing and estimates substantial transfer mispricing in non-tax-haven countries with low- to medium-level corporate tax rates, and in R&D intensive firms. [ABSTRACT FROM AUTHOR]

Background. Birth weight influences not only brain development, but also mental health outcomes, including depression, but the underlying mechanism is unclear. Methods. The phenotypic data of 12,872-91,009 participants (59.18-63.38% women) from UK Biobank were included to test the associations between the birth weight, depression, and brain volumes through the linear and logistic regression models. As birth weight is highly heritable, the polygenic risk scores (PRSs) of birth weight were calculated from the UK Biobank cohort (154,539 participants, 56.90% women) to estimate the effect of birth weight-related genetic variation on the development of depression and brain volumes. Finally, the mediation analyses of step approach and mediation analysis were used to estimate the role of brain volumes in the association between birth weight and depression. All analyses were conducted sex stratified to assess sex-specific role in the associations. Result. Weobserved associations between birth weight and depression (odds ratio [OR] = 0.968, 95% confidence interval [CI] = 0.957-0.979, p = 2.29×10-6). Positive associations were observed between birth weight and brain volumes, such as gray matter (B = 0.131, p = 3.51× 10-74) and white matter (B = 0.129, p = 1.67×10-74). Depression was also associated with brain volume, such as left thalamus (OR = 0.891, 95% CI = 0.850-0.933, p = 4.46×10-5) and right thalamus (OR = 0.884, 95% CI = 0.841-0.928, p = 2.67×10-5). Additionally, significant mediation effects of brain volume were found for the associations between birth weight and depression through steps approach and mediation analysis, such as gray matter (B = -0.220, p = 0.020) and right thalamus (B = -0.207, p = 0.014). Conclusions. Our results showed the associations among birth weight, depression, and brain volumes, and the mediation effect of brain volumes also provide evidence for the sex-specific of associations. [ABSTRACT FROM AUTHOR]

Background: In this commentary we present the findings from an international consortium on fish toxicogenomics sponsored by the U.K. Natural Environment Research Council (Fish Toxicogenomics-Moving into Regulation and Monitoring, held 21-23 April 2008 at the Pacific Environmental Science Centre, Vancouver, BC, Canada). Objectives: The consortium from government agencies, academia, and industry addressed three topics: progress in ecotoxicogenomics, regulatory perspectives on roadblocks for practical implementation of toxicogenomics into risk assessment, and dealing with variability in data sets. Discussion: Participants noted that examples of successful application of omic technologies have been identified, but critical studies are needed to relate molecular changes to ecological adverse outcome. Participants made recommendations for the management of technical and biological variation. They also stressed the need for enhanced interdisciplinary training and communication as well as considerable investment into the generation and curation of appropriate reference omic data. Conclusions: The participants concluded that, although there are hurdles to pass on the road to regulatory acceptance, omics technologies are already useful for elucidating modes of action of toxicants and can contribute to the risk assessment process as part of a weight-of-evidence approach. [ABSTRACT FROM AUTHOR]

Shoulder impingement syndrome (SIS) is a common shoulder disorder with unclear genetic mechanism. In this study, Genome-wide Association Study (GWAS) was conducted to identify the candidate loci associated with SIS by using the UK Biobank samples (including 3,626 SIS patients and 3,626 control subjects). Based on the GWAS results, gene set enrichment analysis was further performed to detect the candidate gene ontology and pathways associated with SIS. We identified multiple risk loci associated with SIS, such as rs750968 (P = 4.82 × 10−8), rs754832 (P = 4.83 × 10−8) and rs1873119 (P = 6.39 × 10−8) of ANXA1 gene. Some candidate pathways have been identified related to SIS, including those linked to infection response and hypoxia, “ZHOU_INFLAMMATORY_RESPONSE_FIMA_DN” (P = 0.012) and “MANALO_HYPOXIA_UP” (P = 5.00 × 10−5). Our results provide novel clues for understanding the genetic mechanism of SIS. [ABSTRACT FROM AUTHOR]