Identifying pleiotropic genes via the composite test amidst the complexity of polygenic traits.

Identifying the causal relationship between genotype and phenotype is essential to expanding our understanding of the gene regulatory network spanning the molecular level to perceptible traits. A pleiotropic gene can act as a central hub in the network, influencing multiple outcomes. Identifying such a gene involves testing under a composite null hypothesis where the gene is associated with, at most, one trait.

Genome-wide multimediator analyses using the generalized Berk-Jones statistics with the composite test.

Motivation: Mediation analysis is performed to evaluate the effects of a hypothetical causal mechanism that marks the progression from an exposure, through mediators, to an outcome. In the age of high-throughput technologies, it has become routine to assess numerous potential mechanisms at the genome or proteome scales. Alongside this, the necessity to address issues related to multiple testing has also arisen.

Hypertension as a Novel Link for Shared Heritability in Age at Menarche and Cardiometabolic Traits.

Context: Extremely early age at menarche, also called precocious puberty, has been associated with various cardiometabolic traits, but their shared heritability remains unclear.

Objectives: This work aimed to identify new shared genetic variants and their pathways for age at menarche and cardiometabolic traits and to investigate the influence of central precocious puberty on childhood cardiometabolic traits.

Methods: Using the conjunction false discovery rate method, this study analyzed genome-wide association study data from the menarche-cardiometabolic traits among 59 655 females of Taiwanese ancestry and systemically investigated pleiotropy between age at menarche and cardiometabolic traits.

NK cell receptor and ligand composition influences the clearance of SARS-CoV-2.

To explore how the immune system controls clearance of SARS-CoV-2, we used a single-cell, mass cytometry-based proteomics platform to profile the immune systems of 21 patients who had recovered from SARS-CoV-2 infection without need for admission to an intensive care unit or for mechanical ventilation. We focused on receptors involved in interactions between immune cells and virus-infected cells. We found that the diversity of receptor repertoires on natural killer (NK) cells was negatively correlated with the viral clearance rate.

Estimating the causal effect of embryo transfer day on clinical in vitro fertilization outcomes using propensity score matching.

Background: For women undergoing in vitro fertilization (IVF), the clinical benefit of embryo transfer at the blastocyst stage (Day 5) versus cleavage stage (Day 3) remains controversial. The purpose of this study is to compare the implantation rate, clinical pregnancy rate and odds of live birth of Day 3 and Day 5 embryo transfer, and more importantly, to address the issue that patients were chosen to receive either transfer protocol due to their underlying clinical characteristics, i.e.

A mediation analysis for a nonrare dichotomous outcome with sequentially ordered multiple mediators.

Mediation analyses can help us to understand the biological mechanism in which an exposure or treatment affects an outcome. Single mediator analyses have been used in various applications, but may not be appropriate for analyzing intricate mechanisms involving multiple mediators that affect each other. Thus, in this article, we studied multiple sequentially ordered mediators for a dichotomous outcome and presented the identifiability assumptions for the path-specific effects on the outcome, that is, the effect of an exposure on the outcome mediated by a specific set of mediators.

Drug Class, Renal Elimination, and Outcomes of Direct Oral Anticoagulants in Asian Patients: A Meta-Analysis.

Background: Direct oral anticoagulants (DOACs) have a better risk benefit profile in Asian patients with atrial fibrillation (AF). Whether treatment effects could be modified by drug class and dependency on renal elimination of studied agents has not yet been explored.

Methods: We searched PubMed, CENTRAL, and CINAHL databases through November 2016 for phase III randomized controlled trials comparing DOACs with warfarin in patients with AF.

Once- or twice-daily non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: A meta-analysis of randomized controlled trials.

Background/purpose: Non-vitamin K antagonist oral anticoagulants (NOACs) have a half-life of around 12 h. We aimed to clarify if there was any effect modification by dosing (once- or twice-daily) regimens in Asian patients.

Methods: Phase III randomized controlled trials of NOACs compared with warfarin in Asian patients with atrial fibrillation (AF) were identified and extracted from PubMed, CENTRAL, and CINAHL databases through November 2016.

A knowledge-based T2-statistic to perform pathway analysis for quantitative proteomic data.

Approaches to identify significant pathways from high-throughput quantitative data have been developed in recent years. Still, the analysis of proteomic data stays difficult because of limited sample size. This limitation also leads to the practice of using a competitive null as common approach; which fundamentally implies genes or proteins as independent units.

Extracranial arterial and venous thromboembolism in patients with atrial fibrillation: A meta-analysis of randomized controlled trials.

Background: Thromboembolism prevention is central to atrial fibrillation (AF) management. Randomized controlled trials (RCTs) have primarily focused on stroke prevention. Detailed analyses of extracranial thromboembolic events, particularly in patients with low dose non-vitamin K antagonist oral anticoagulants (NOACs), are scarce.

Standard dose versus low dose non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: A meta-analysis of contemporary randomized controlled trials.

Background: Although randomized controlled trials (RCTs) indicated that standard dose non-vitamin K antagonist oral anticoagulants (NOACs) were more compelling, low dose NOACs are commonly used in clinical practice in Asia.

Objective: The purpose of this study was to assess the relative therapeutic benefit and risk of standard dose vs low dose NOACs in Asian patients enrolled in contemporary RCTs.

Methods: We performed a prespecified meta-analysis of 3155 Asian patients with NOACs in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) and ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trials.

A linear-time algorithm for reconstructing zero-recombinant haplotype configuration on a pedigree.

Background: When studying genetic diseases in which genetic variations are passed on to offspring, the ability to distinguish between paternal and maternal alleles is essential. Determining haplotypes from genotype data is called haplotype inference. Most existing computational algorithms for haplotype inference have been designed to use genotype data collected from individuals in the form of a pedigree.