Clade Distillation for Genome-wide Association Studies.

Testing inferred haplotype genealogies for association with phenotypes has been a longstanding goal in human genetics given their potential to detect association signals driven by allelic heterogeneity - when multiple causal variants modulate a phenotype - in both coding and noncoding regions. Recent scalable methods for inferring locus-specific genealogical trees along the genome, or representations thereof, have made substantial progress towards this goal; however, the problem of testing these trees for association with phenotypes has remained unsolved due to the growth in the number of clades with increasing sample size. To address this issue, we introduce several practical improvements to the kalis ancestry inference engine, including a general optimal checkpointing algorithm for decoding hidden Markov models, thereby enabling efficient genome-wide analyses.

Differences in Mental Illness Stigma by Disorder and Gender: Population-Based Vignette Randomized Experiment in Rural Uganda.

Understanding and eliminating mental illness stigma is crucial for improving population mental health. In many settings, this stigma is gendered, from the perspectives of both the stigmatized and the stigmatizers. We aimed to find the differences in the level of stigma across different mental disorders while considering the gender of the study participants as well as the gender of the people depicted in the vignettes.

kalis: a modern implementation of the Li & Stephens model for local ancestry inference in R.

Background: Approximating the recent phylogeny of N phased haplotypes at a set of variants along the genome is a core problem in modern population genomics and central to performing genome-wide screens for association, selection, introgression, and other signals. The Li & Stephens (LS) model provides a simple yet powerful hidden Markov model for inferring the recent ancestry at a given variant, represented as an distance matrix based on posterior decodings.

Results: We provide a high-performance engine to make these posterior decodings readily accessible with minimal pre-processing via an easy to use package kalis, in the statistical programming language R.

Evaluation of a pilot, community-led mental illness de-stigmatization theater intervention in rural uganda.

Background: In rural areas of low- and middle- income countries, mental health care is often unavailable and inaccessible, and stigma is a major barrier to treatment. Destigmatization can increase treatment-seeking attitudes, community support, and acceptance of individuals suffering from mental illness. This study's primary objective was to evaluate the impact of a community-led, theater-based destigmatization campaign for mental illness conducted in the Busoga region of Eastern Uganda.

An Epidemic Amidst a Pandemic: Musculoskeletal Firearm Injuries During the COVID-19 Pandemic.

Background: The COVID-19 pandemic has substantially impacted the delivery of health care, both through direct care associated with COVID-19 and through more pervasive effects. Our goal was to evaluate whether the number of orthopaedic consultations for firearm injuries differed during the early months of the COVID-19 pandemic compared with the same period in prior years. We hypothesized that the initial months of the COVID-19 pandemic, compared with the same period in prior years, would have a higher number of orthopaedic consultations for firearm injuries and a lower rate of outpatient follow-up after consultations.

Mitochondrial genome copy number measured by DNA sequencing in human blood is strongly associated with metabolic traits via cell-type composition differences.

Background: Mitochondrial genome copy number (MT-CN) varies among humans and across tissues and is highly heritable, but its causes and consequences are not well understood. When measured by bulk DNA sequencing in blood, MT-CN may reflect a combination of the number of mitochondria per cell and cell-type composition. Here, we studied MT-CN variation in blood-derived DNA from 19184 Finnish individuals using a combination of genome (N = 4163) and exome sequencing (N = 19034) data as well as imputed genotypes (N = 17718).

Association of structural variation with cardiometabolic traits in Finns.

The contribution of genome structural variation (SV) to quantitative traits associated with cardiometabolic diseases remains largely unknown. Here, we present the results of a study examining genetic association between SVs and cardiometabolic traits in the Finnish population. We used sensitive methods to identify and genotype 129,166 high-confidence SVs from deep whole-genome sequencing (WGS) data of 4,848 individuals.

Multicohort analysis of the maternal age effect on recombination.

Several studies have reported that the number of crossovers increases with maternal age in humans, but others have found the opposite. Resolving the true effect has implications for understanding the maternal age effect on aneuploidies. Here, we revisit this question in the largest sample to date using single nucleotide polymorphism (SNP)-chip data, comprising over 6,000 meioses from nine cohorts.