Biology subjects

Wyss, A. B.

Publications and source records attributed to Wyss, A. B..

3 recordsLinked to original sources

bioRxiv2026

ScreenDMT reveals metabolites replicably associated with sleep disorders across three human cohorts

The robust replication of scientific findings across independent studies is essential, yet it remains challenging in high-dimensional biological datasets. A critical aspect of true replication requires detecting not only the repeated presence but also the consistent direction of an effect. Traditional methods for evaluating replication often ignore effect directionality or lack adequate statistical power when adjusting for multiple comparisons. To address this, we extend the directional MaxP test (DMT) and our screening-integrated procedure, ScreenDMT, to evaluate directional replication across an arbitrary number of independent studies. We mathematically prove ScreenDMT's validity for an arbitrary number of studies when the studies' sample sizes grow unbounded. Through extensive simulation studies, we demonstrate that ScreenDMT effectively controls error rates, such as the false discovery rate (FDR), in finite sample sizes and yields higher statistical power than competing methods especially for three studies. We applied the extended ScreenDMT to untargeted blood metabolomics profiles across three diverse human cohorts - ARIC (N=1,337), MESA (N=1,874), and HCHS/SOL (N=6,180) - to discover replicable biomarkers for dichotomous insomnia, long sleep, short sleep, and excessive daytime sleepiness (EDS). We found low levels of cortisol to be replicably associated with EDS, and high levels of n-formylmethionine to be associated with long sleep. Furthermore, directional pathway analysis revealed that low levels of xanthine metabolites are replicably associated with insomnia. These convergent findings validate ScreenDMT as a powerful methodology for simultaneous multi-cohort replication and offer robust insights into the metabolic signatures underlying sleep disorders across diverse populations.

bioinformatics↗

bioRxiv2018

Expanded genetic landscape of chronic obstructive pulmonary disease reveals heterogeneous cell type and phenotype associations

Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide novel insights into disease pathogenesis. To broaden COPD genetic risk loci discovery and identify cell type and phenotype associations we performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci with P value < 5x10-8; 47 were previously described in association with either COPD or population-based lung function. Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and alveolar type II cells. We found 9 shared genomic regions between COPD and asthma and 5 between COPD and pulmonary fibrosis. COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations. Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD.

genetics↗

bioRxiv2017

Multiethnic Meta-analysis Identifies New Loci for Pulmonary Function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N=60,552), African (N=8,429), Asian (N=9,959), and Hispanic/Latino (N=11,775) ethnicities. We identified over 50 novel loci at genome-wide significance in ancestry-specific and/or multiethnic meta-analyses. Recent fine mapping methods incorporating functional annotation, gene expression, and/or differences in linkage disequilibrium between ethnicities identified potential causal variants and genes at known and newly identified loci. Sixteen of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12.

genetics↗