Volume 54 Issue 4, April 2022

Widespread enthusiasm about potential contributions of genome-edited crops to address climate change, food security, nutrition and health, environmental sustainability and diversification of agriculture is dampened by concerns about the associated risks. Analysis of the top seven risks of genome-edited crops finds that the scientific risks are comparable to those of accepted, past and current breeding methods, but failure to address regulatory, legal and trade framework, and the granting of social license, squanders the potential benefits.

Defining the most appropriate phenotypes in genome-wide association studies of COVID-19 is challenging, and two new publications demonstrate how case-control definitions critically determine outcomes and downstream clinical utility of findings.

Chromosomes are shaped by an interplay between loop extrusion and compartmentalization. Two new studies demonstrate that bromodomain and extraterminal domain (BET) proteins contribute to both processes, with BRD4 facilitating one process and surprisingly inhibiting the other.

The largest genetic study of educational attainment (EA) so far combines gene mapping and family analyses to show that genetic associations with EA and its health benefits may be mostly indirect. As such, future genetic studies of human social and behavioral traits must include diversity in population, demographic and environmental contexts.

GWASs based on self-reported phenotypes in 736,723 individuals show distinct associations between risk loci and eight COVID-19 outcomes, suggesting differences in genetic susceptibility to infection upon exposure and severe and symptomatic disease.

Genome-wide meta-analysis of SARS-CoV-2 susceptibility and severity phenotypes in up to 756,646 samples identifies a rare protective variant proximal to ACE2. A 6-SNP genetic risk score provides additional predictive power when added to known risk factors.

Genetic analyses identify associations between T cell antigen receptor composition at complementarity-determining region 3 and specific HLA alleles, including position 13 of HLA-DRB1, which mediates risk for multiple autoimmune diseases.

A genome-wide study based on three-dimensional facial images identifies new loci associated with facial morphology in East Asian populations. Comparison with data from European populations identifies variants related to facial shape differences between these populations.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

PolyPred and PolyPred⁺ methods that leverage fine-mapping and non-European training data significantly improve cross-population polygenic prediction accuracy when applied to diseases and complex traits in UK Biobank populations.

Single-cell multiomic profiling of triple-negative breast cancer samples treated with capecitabine shows that H3K27me3 regulates a persister cell state. Blocking H3K27me3 demethylation inhibits the transition to a drug-tolerant state and delays tumor recurrence.

In the male germline, DNMT3C methylates retrotransposons whereas DNMT3A globally methylates the genome and regulates spermatogonial stem cell (SSC) plasticity. Single-cell RNA-sequencing analysis shows that Dnmt3A mutant SSCs self-renew but do not differentiate.

BRD2 facilitates mixing and compartmentalization of active chromatin upon cohesin depletion. BRD2’s function is counteracted by cohesin and BRD4.

Single-cell whole-genome sequencing of proximal bronchial basal cells shows that somatic mutations accumulate with age and at a higher level in smokers compared to never-smokers. Mutation frequencies increased with smoking dose but then plateaued, suggesting intrinsic mechanisms to limit mutation burden.

Analyses on the global diversity of SARS-CoV-2 genomic surveillance across 118 countries and the extent of public availability of genomic data provide evidence to better inform SARS-CoV-2 surveillance policy.

Association analyses using resting-state functional magnetic resonance images identify common genetic variants influencing intrinsic brain activity. Variation in brain function is genetically correlated with several neuropsychiatric traits.

PanGenie is an alignment-free, k-mer-based tool that utilizes a haplotype-resolved pangenome reference to genotype a wide range of variants.