Identification of multi-omic pleiotropy factors for peripheral artery disease.

Background: Peripheral artery disease (PAD) is prevalent and frequently co-occurs with type 2 diabetes (T2D) and coronary artery disease (CAD). Although shared genetic factors may contribute to these comorbidities, few studies have examined pleiotropy at the transcriptomic and proteomic levels.

Methods: We generated summary statistics for transcriptome-wide (TWAS) and proteome-wide (PWAS) association analyses across PAD, T2D, and CAD.

Saddlepoint approximations to score test statistics in logistic regression for analyzing genome-wide association studies.

We investigate saddlepoint approximations of tail probabilities of the score test statistic in logistic regression for genome-wide association studies. The inaccuracy in the normal approximation of the score test statistic increases with increasing imbalance in the response and with decreasing minor allele counts. Applying saddlepoint approximation methods greatly improve the accuracy, even far out in the tails of the distribution.

Inferring feature importance with uncertainties with application to large genotype data.

Estimating feature importance, which is the contribution of a prediction or several predictions due to a feature, is an essential aspect of explaining data-based models. Besides explaining the model itself, an equally relevant question is which features are important in the underlying data generating process. We present a Shapley-value-based framework for inferring the importance of individual features, including uncertainty in the estimator.

Preimplantation genetic testing for aneuploidy: challenges in clinical practice.

Preimplantation genetic testing for aneuploidy (PGT-A) has been used widely during in vitro fertilization procedures in assisted reproductive centers throughout the world. Despite its wide use, concerns arise from the use of PGT-A technology in clinical decision-making. We address knowledge gaps in PGT-A, summarizing major challenges and current professional guidelines.

Rates of Neuropsychiatric Disorders and Gestational Age at Birth in a Danish Population.

Importance: Nonoptimal gestational durations could be associated with neurodevelopmental disabilities, yet evidence regarding finer classification of gestational age and rates of multiple major neuropsychiatric disorders beyond childhood is limited.

Objective: To comprehensively evaluate associations between 6 gestational age groups and rates of 9 major types and 8 subtypes of childhood and adult-onset neuropsychiatric disorders.

Design, Setting, And Participants: This cohort study evaluated data from a nationwide register of singleton births in Denmark from January 1, 1978, to December 31, 2016.

A new method for exploring gene-gene and gene-environment interactions in GWAS with tree ensemble methods and SHAP values.

Background: The identification of gene-gene and gene-environment interactions in genome-wide association studies is challenging due to the unknown nature of the interactions and the overwhelmingly large number of possible combinations. Parametric regression models are suitable to look for prespecified interactions. Nonparametric models such as tree ensemble models, with the ability to detect any unspecified interaction, have previously been difficult to interpret.

Genome-Wide Linkage Analysis of the Risk of Contracting a Bloodstream Infection in 47 Pedigrees Followed for 23 Years Assembled From a Population-Based Cohort (the HUNT Study).

Objectives: Bloodstream infection is an important cause of death worldwide. The main objective of this study was to identify genetic loci linked to risk of contracting a bloodstream infection.

Design: Genome-wide linkage analysis.

The Role of FER rs4957796 in the Risk of Developing and Dying from a Bloodstream Infection: A 23-Year Follow-up of the Population-based Nord-Trøndelag Health Study.

Background: Bloodstream infection and sepsis are major causes of health loss worldwide, and it is important to identify patients at risk of developing and dying from these conditions. The single-nucleotide polymorphism most strongly associated with sepsis mortality is FER rs4957796. However, it is not known how this variant is associated with bloodstream infection incidence and mortality.