It has been postulated that rare coding variants (RVs; MAF < 0.01) contribute to the "missing" heritability of complex traits. We developed a framework, the Rare variant heritability (RARity) estimator, to assess RV heritability (h) without assuming a particular genetic architecture.
View Article and Find Full Text PDFPost-fermented tea (PFT), a commonly consumed beverage worldwide, is characterized by the rapid growth of its microbial groups and the substantial changes they undergo. Consequently, PFT may contain mycotoxins such as B-type fumonisins (FBs). This study aimed to assess the intake of FBs through the consumption of PFT among consumers in Guangxi, China.
View Article and Find Full Text PDFImportance: Body mass index (BMI) is an easily obtained adiposity surrogate. However, there is variability in body composition and adipose tissue distribution between individuals with the same BMI, and there is controversy regarding the BMI associated with the lowest mortality risk.
Objective: To evaluate which of BMI, fat mass index (FMI), and waist-to-hip (WHR) has the strongest and most consistent association with mortality.
Identification of gene-by-environment interactions (GxE) is crucial to understand the interplay of environmental effects on complex traits. However, current methods evaluating GxE on biobank-scale datasets have limitations. We introduce MonsterLM, a multiple linear regression method that does not rely on model specification and provides unbiased estimates of variance explained by GxE.
View Article and Find Full Text PDFBackground: Atherosclerotic cardiovascular diseases (CVDs) are leading causes of death despite effective therapies and result in unnecessary morbidity and mortality throughout the world. We aimed to investigate the cost-effectiveness of polygenic risk scores (PRS) to guide statin therapy for Canadians with intermediate CVD risk and model its economic outlook.
Methods: This cost-utility analysis was conducted using UK Biobank prospective cohort study participants, with recruitment from 2006 to 2010, and at least 10 years of follow-up.
Gestational diabetes Mellitus (GDM) affects 1 in 7 births and is associated with numerous adverse health outcomes for both mother and child. GDM is suspected to share a large common genetic background with type 2 diabetes (T2D). The aim of our study was to characterize different GDM polygenic risk scores (PRSs) and test their association with GDM using data from the South Asian Birth Cohort (START).
View Article and Find Full Text PDFTo explore the relationship between the moisture content of withered tea leaves and their physical properties (i.e., elasticity, plasticity, flexibility, and texture) during withering, texture analyzer was employed to test the elasticity and flexibility of withered tea leaves with different moisture contents.
View Article and Find Full Text PDFAn amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFGenotype-stratified variance of a quantitative trait could differ in the presence of gene-gene or gene-environment interactions. Genetic markers associated with phenotypic variance are thus considered promising candidates for follow-up interaction or joint location-scale analyses. However, as in studies of main effects, the X-chromosome is routinely excluded from "whole-genome" scans due to analytical challenges.
View Article and Find Full Text PDFObjective: Observations of a metabolically unhealthy normal weight phenotype suggest that a lack of favorable adiposity contributes to an increased risk of type 2 diabetes. We aimed to identify causal blood biomarkers linking favorable adiposity with type 2 diabetes risk for use in cardiometabolic risk assessments.
Research Design And Methods: A weighted polygenic risk score (PRS) underpinning metabolically favorable adiposity was validated in the UK Biobank ( = 341,872) and the Outcome Reduction With Initial Glargine Intervention (ORIGIN Trial) ( = 8,197) and tested for association with 238 blood biomarkers.
Complex traits can share a substantial proportion of their polygenic heritability. However, genome-wide polygenic correlations between pairs of traits can mask heterogeneity in their shared polygenic effects across loci. We propose a novel method (weighted maximum likelihood-regional polygenic correlation [RPC]) to evaluate polygenic correlation between two complex traits in small genomic regions using summary association statistics.
View Article and Find Full Text PDFBackground: Gas chromatography-olfactometry (GC-O) is the most frequently used method to estimate the sensory contribution of single odorant, but disregards the interactions between volatiles. In order to select the key volatiles responsible for the aroma attributes of Congou black tea (Camellia sinensis), instrumental, sensory and multivariate statistical approaches were applied.
Results: Using sensory analysis, nine panellists developed eight descriptors: floral, sweet, fruity, green, roasted, oil, spicy, and off-odour.
Machine-learning techniques have helped solve a broad range of prediction problems, yet are not widely used to build polygenic risk scores for the prediction of complex traits. We propose a novel heuristic based on machine-learning techniques (GraBLD) to boost the predictive performance of polygenic risk scores. Gradient boosted regression trees were first used to optimize the weights of SNPs included in the score, followed by a novel regional adjustment for linkage disequilibrium.
View Article and Find Full Text PDFDespite considerable efforts, known genetic associations only explain a small fraction of predicted heritability. Regional associations combine information from multiple contiguous genetic variants and can improve variance explained at established association loci. However, regional associations are not easily amenable to estimation using summary association statistics because of sensitivity to linkage disequilibrium (LD).
View Article and Find Full Text PDFA significant challenge to the effective application of RNA-seq to the complete transcript analysis of low quantity and/or degraded samples is the amplification of minimal input RNA to enable sequencing library construction. Several strategies have been commercialized in order to facilitate this goal. However, each strategy has its own specific protocols and methodology, and each may introduce unique bias and in some cases show specific preference for a collection of sequences.
View Article and Find Full Text PDFDifferent semen storage and sperm purification methods may affect the integrity of isolated spermatozoal RNA. RNA-Seq was applied to determine whether semen storage methods (pelleted vs. liquefied) and somatic cell lysis buffer (SCLB) vs.
View Article and Find Full Text PDFMammographic screening leads to frequent biopsies and concomitant overdiagnosis of breast cancer, particularly ductal carcinoma in situ (DCIS). Some DCIS lesions rapidly progress to invasive carcinoma, whereas others remain indolent. Because we cannot yet predict which lesions will not progress, all DCIS is regarded as malignant, and many women are overtreated.
View Article and Find Full Text PDFIncreasing attention has focused on the significance of RNA in sperm, in light of its contribution to the birth and long-term health of a child, role in sperm function and diagnostic potential. As the composition of sperm RNA is in flux, assigning specific roles to individual RNAs presents a significant challenge. For the first time RNA-seq was used to characterize the population of coding and non-coding transcripts in human sperm.
View Article and Find Full Text PDFBreast ductal carcinoma in situ (DCIS) is being found in great numbers of women due to the widespread use of mammography. To increase knowledge of DCIS, we determined the expression changes that are common among three DCIS models (MCF10.DCIS, SUM102 and SUM225) compared to the MCF10A model of non-tumorigenic mammary epithelial cells in three dimensional (3D) overlay culture with reconstituted basement membrane (rBM).
View Article and Find Full Text PDFThe detection, identification, and quantitation of transcripts have evolved from simple Northern analysis, cDNA cloning, and sequencing to RT-PCR, microarrays, and now digital gene expression using ultra-high-throughput RNA sequencing (RNA-Seq). During the course of our studies we observed that some microarray probes show very high signal intensity values yet are discordant when compared with RNA-Seq. A total of 99 probes from approximately 30,000 were identified as consistently discordant in four human tissues or cell lines.
View Article and Find Full Text PDFNumerous studies have focused on the transcriptional signatures that underlie the maintenance of embryonic stem cell (ESC) pluripotency. However, it remains unclear whether ESC retain transcriptional aberrations seen in in vitro cultured embryos. Here we report the first global transcriptional profile comparison between ESC generated from either in vitro cultured or in vivo derived primate embryos by microarray analysis.
View Article and Find Full Text PDFGABA depolarizes and excites central neurons during early development, becoming inhibitory and hyperpolarizing with maturation. This "developmental shift" occurs abruptly, reflecting a decrease in intracellular Cl(-) concentration ([Cl(-)](i)) and a hyperpolarizing shift in Cl(-) equilibrium potential due to upregulation of the K(+)-Cl(-) cotransporter KCC2b, a neuron-specific Cl(-) extruder. In contrast, primary afferent neurons (PANs) are depolarized by GABA throughout adulthood because of expression of NKCC1, a Na(+)-K(+)-2Cl(-) cotransporter that accumulates Cl(-) above equilibrium.
View Article and Find Full Text PDFObjective: To investigate the potential use of correlative microarray-based transcript pairs as candidate markers for male fertility using dysplasia of the fibrous sheath (DFS) as an affected model. It is widely recognized that microarray technology may be limited by cost and that the quality of the transcript remains relatively unknown. To address these issues, we analyzed the stable transcript pairs by qPCR with a systematic primer design process.
View Article and Find Full Text PDFActivation of the major histocompatibility complex (MHC) by interferon-gamma (IFN-γ) is a fundamental step in the adaptive immune response to pathogens. Here, we show that reorganization of chromatin loop domains in the MHC is evident within the first 30 min of IFN-γ treatment of fibroblasts, and that further dynamic alterations occur up to 6 h. These very rapid changes occur at genomic sites which are occupied by CTCF and are close to IFN-γ-inducible MHC genes.
View Article and Find Full Text PDFMicroarray technology has great potential for improving our understanding of biological processes, medical conditions, and diseases. Often, microarray datasets are collected using different microarray platforms (provided by different companies) under different conditions in different laboratories. The cross-platform and cross-laboratory concordance of the microarray technology needs to be evaluated before it can be successfully and reliably applied in biological/clinical practice.
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