Association between depression and sleep apnoea: a Mendelian randomisation study

BackgroundStudies have reported a close relationship between depression and sleep apnoea, yet it is unknown whether these are causally related. Thus, we aimed to determine whether depression is associated with the aetiology of sleep apnoea.MethodsWe used publicly available genetic summary data from two large consortia, the Psychiatric Genomics Consortium, with data from 36 single-nucleotide polymorphisms (SNPs) closely associated with major depressive disorder (MDD) and UK Biobank, including 456 736 patients with sleep apnoea and 766 964 controls. For Mendelian randomisation (MR) analysis, we used the inverse-variance weighted method, weighted median method, MR-Egger regression, MR pleiotropy residual sum, and outlier test to retrieve summary data. Analyses were performed using the “TwoSampleMR” package in R.ResultsOf the 36 SNPs associated with MDD, we found statistically significant evidence of a potential causal effect of MDD on the risk of sleep apnoea (odds ratio 1.004, 95% confidence interval: 1.001–1.006, p=0.001). Similar results were obtained using the MR-Egger and weighted median methods. Additionally, we found no heterogeneity or pleiotropy.ConclusionsOur findings suggest that depression slightly increases the risk of sleep apnoea. Further investigation of the potential biological mechanisms is necessary.

Childhood Obesity and Risk of Stroke: A Mendelian Randomisation Analysis

Background: The causal relationship between childhood obesity and stroke remains unclear. Our objective was to elucidate the causal relationship between childhood obesity and the risk of stroke and its subtypes by performing Mendelian randomisation (MR) analyses.Methods: Genetic instruments for childhood obesity were obtained from a genome-wide association study (GWAS) of 13,848 European participants. Summary level data for stroke, intracerebral haemorrhage, ischaemic stroke (IS), and its subtypes were evaluated using the MEGASTROKE GWAS dataset, which included 446,696 European adults. Inverse-variance weighting, weighted-median analysis, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO), and MR-Robust Adjusted Profile Score were applied in this MR analysis. The leave-one-out sensitivity test, MR-PRESSO Global test, and Cochran’s Q test were conducted to confirm the accuracy and robustness of our results.Results: Genetic evaluations revealed that childhood obesity was associated with a higher risk of stroke (OR = 1.04, 95%CI: 1.01–1.07, p = 0.005) and IS (OR = 1.05, 95%CI: 1.02–1.08, p = 0.003), but not with intracerebral haemorrhage (ICH, OR = 0.93, 95%CI: 0.80–1.09, p = 0.39). In the subtype analysis, childhood obesity was also associated with large artery stroke (LAS, OR = 1.12, 95%CI: 1.02–1.22, p = 0.016) but not with cardioembolic stroke (OR = 1.06, 95%CI: 0.96–1.18, p = 0.21) and small vessel stroke (OR = 1.06, 95%CI: 0.98–1.15, p = 0.17). These results were stable in the sensitivity analysis and remained significant after Bonferroni correction.Conclusion: Our study provides evidence that childhood obesity is associated with a higher risk of stroke, IS, and LAS. The prevention of stroke, especially IS and LAS, should be promoted in populations with childhood obesity.

Genetically Determined Serum 25-Hydroxyvitamin D Is Associated with Total, Trunk, and Arm Fat-Free Mass: A Mendelian Randomization Study

Purpose Low serum vitamin D status has been associated with reduced muscle mass in observational studies although the relationship is controversial and a causal association cannot be determined from such observations. Two-sample Mendelian randomization (MR) was applied to assess the association between serum vitamin D (25(OH)D) and total, trunk, arm and leg fat-free mass (FFM). Methods MR was implemented using summary-level data from the largest genome-wide association studies (GWAS) on vitamin D (n=73,699) and total, trunk, arm and leg FFM. Inverse variance weighted method (IVW) was used to estimate the causal estimates. Weighted median (WM)-based method, and MR-Egger, leave-one-out were applied as sensitivity analysis. Results Genetically higher serum 25(OH)D levels had a positive effect on total (IVW = Beta: 0.042, p = 0.038), trunk (IVW = Beta: 0.045, p = 0.023) and arm (right arm IVW = Beta: 0.044, p = 0.002; left arm IVW = Beta: 0.05, p = 0.005) FFM. However, the association with leg FFM was not significant (right leg IVW = Beta: 0.03, p = 0.238; left leg IVW = Beta: 0.039, p = 0.100). The likelihood of heterogeneity and pleiotropy was determined to be low (statistically non-significant), and the observed associations were not driven by single SNPs. Furthermore, MR pleiotropy residual sum and outlier test did not highlight any outliers. Conclusions Our results illustrate the potentially causal, positive effect of serum 25(OH)D concentration on total, trunk and upper body appendicular fat-free mass.

On the Upper Bounds of Test Statistics for a Single Outlier Test in Linear Regression Models

A bewildering large number of test statistics have been found for testing the presence of an outlier in multiple linear regression models. Exact critical values of these test statistics are not available, and approximate ones are usually obtained by the first-order Bonferroni upper bound or large-scale simulations. In this paper, we show that the upper bound values of two of these test statistics are algebraically the same. An application to real data for multiple linear regression is used to demonstrate the procedure.

Post-genotyping optimization of dataset formation could affect genetic diversity parameters: an example of analyses with alpine goat breeds

Background Local breeds retained unique genetic variability important for adaptive potential especially in light of challenges related to climate change. Our first objective was to perform, for the first time, a genome-wide diversity characterization using Illumina GoatSNP50 BeadChip of autochthonous Drežnica goat breed from Slovenia, and five and one local breeds from neighboring Austria and Italy, respectively. For optimal conservation and breeding programs of endangered local breeds, it is important to detect past admixture events and strive for preservation of purebred representatives of each breed with low or without admixture. In the second objective, we hence investigated the effect of inclusion or exclusion of outliers from datasets on genetic diversity and population structure parameters. Results Distinct genetic origin of the Drežnica goat was demonstrated as having closest nodes to Austrian and Italian breeds. A phylogenetic study of these breeds with other goat breeds having SNP data available in the DRYAD repository positioned them in the alpine, European and global context. Swiss breeds clustered with cosmopolitan alpine breeds and were closer to French and Spanish breeds. On the other hand, the Drežnica goat, Austrian and Italian breeds were closer to Turkish breeds. Datasets where outliers were excluded affected estimates of genetic diversity parameters within the breed and increased the pairwise genetic distances between most of the breeds. Alpine breeds, including Drežnica, Austrian and Italian goats analyzed here, still exhibit relatively high levels of genetic variability, homogeneous genetic structure and strong geographical partitioning. Conclusions Genetic diversity analyses revealed that the Slovenian Drežnica goat has a distinct genetic identity and is closely related to the neighboring Austrian and Italian alpine breeds. These results expand our knowledge on phylogeny of goat breeds from easternmost part of the European Alps. The here employed outlier test and datasets optimization approaches provided an objective and statistically powerful tool for removal of admixed outliers. Importance of this test in selecting the representatives of each breed is warranted to obtain more objective diversity parameters and phylogenetic analysis. Such parameters are often the basis of breeding and management programs and are therefore important for preserving genetic variability and uniqueness of local rare breeds.

DETERMINAN BID-ASK SPREAD PERUSAHAAN YANG MELAKSANAKAN KEBIJAKAN STOCK SPLIT TAHUN 2016-2019

Studi ini dilakukan guna mencari tahu adakah kontribusi harga saham, volume perdagangan saham, dan return saham atas bid-ask sread pada perusahaan yang melaksanakan kebijakan stock split di Bursa Efek Indonesia tahun 2016 hingga 2019. Penelitian tergolong dalam penelitian kuantitatif. Pengambilan sampel ditentukan dengan memakai purposive sampling. Terdapat beberapa pengujian yang dipakai pada penelitian ini yaitu uji outlier, uji normalitas, uji asumsi klasik, analisis regresi linear berganda, uji hipotesis. Berdasarkan uji parsial yang dilakukan diperoleh hasil yaitu harga saham dan volume perdagangan saham bepengaruh negatif signifikan terhadap bid-ask, serta return saham berpengaruh positif signifikan terhadap bid-ask spread. Thisstudy aims to determine the effect ofstockprices,tradingvolumeactivity,andstockreturns on thebid-askspreadin companiesthatdostocksplitslistedontheIndonesiaStockExchangein 2016 to 2019. Thisresearchisincludedinthecategoryofquantitativeresearch. Sampling in this study was determined by using purposive sampling method. There are several tests used in this study, the analytical method used, outlier test, normality test, classical assumptions, consists of multiple regression analysis , hypothesis testing (t test) and the coefficient of determination test.Based on the partial test conducted, the results obtained that stock prices and tradingvolumeactivity have anegativeandsignificant effect on the bid-ask spread, and stock returns have apositive andsignificant effect on the bid-ask spread

DETERMINANTS OF A COUNTRY’S GNP TO GDP POSITION: A REVISIT

In memoriam Professor Eu Chye TAN The Singapore Economic Review express sincere gratitude for the work done by Professor Tan serving on its Editorial Board from 2017–2020. The aim of this paper is to identify the factors that could contribute to an increase in a country’s GNP relative to its GDP. This represents a sequel to [Tan, EC, CF Tang and RD Palaniandi (2019). What could cause a country’s GNP to be greater than its GDP? Singapore Economic Review, doi:10.1142/S0217590819500073.] on what could cause a country’s GNP to exceed its GDP. Annual data of a panel of 52 countries from 1992 through 2016 are mobilized for the purpose, with the sample period split into five-year average intervals. The possible determinants of the relative position include the savings-investment gap, international reserves, state of technology, demography, unemployment, export-orientation, income inequality, size of the primary commodities sector, financial repression, tax incidence and the ease of doing business. Based upon the application of the system GMM technique to winsorized data and filtered data from Cook’s Distance Outlier Test, the savings-investment gap could enhance the GNP–GDP percentage of a country. The percentage could be lowered by export orientation, uneven income distribution and the size of the working age population.

Pengaruh Pembiayaan Mudharabah, Musyarakah dan Murabahah Terhadap Profitabilitas Bank Umum Syariah

This study aims to analyze the effect of mudharabah, musyarakah, and murabahah financing on the level of profitability in banks using the Return on Assets (ROA) ratio simultaneously and partially. The sample used in this study was 42 data from the results of the outlier test which previously had 52 sample data into 42 sample data with the study population using 7 (seven) Islamic commercial banks until 2019. The data analysis method used in this study was multiple linear regression of panel data. The results of this study indicate that partially mudharabah financing has no significant negative effect on the level of profitability, while musharaka partially has a negative effect on the level of profitability. Murabahah financing has a significant positive effect on profitability.

Association Between Circulating Linoleic Acid and Risk of Ischemic Stroke

BackgroundObservational studies have shown an inverse association between circulating linoleic acid (LA) and risk of ischemic stroke (IS).ObjectiveThe aim of this study was to explore whether genetic variants predicting levels of circulating LA are associated with IS and its subtypes using a two-sample Mendelian randomization (MR) analysis.MethodsLA-related single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of 8,631 participants, and summary statistics of IS and IS subtypes were obtained from the MEGASTROKE consortium. MR analysis was performed using the inverse-variance weighted (IVW) method complemented with other approaches, including weighted-median, weighted-mode, MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression, to test for the robustness of the association. Moreover, we conducted bidirectional MR analysis to assess the impact of IS-associated SNPs on circulating LA levels. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.ResultsWe found that genetically predicted circulating LA levels were inversely associated with the risk of IS by the IVW method (OR = 0.98, 95% CI: 0.97–0.99, and P = 0.003). Subgroup analyses showed a statistically significant association between LA and risk of large artery stroke (LAS; OR = 0.95, 95% CI: 0.92–0.98, and P = 0.004), but not for other IS subtypes. The results were stable in sensitivity analyses, and no evidence of reverse association between LA and risk of IS, or LAS was observed.ConclusionOur study supports a potential inverse association of genetically predicted circulating LA levels with risk of IS, particularly LAS.