Volume 50 Issue 7, July 2018

Meta-analysis of genome-wide association studies for cognitive ability identifies 190 new loci and implicates 939 new genes related to neurogenesis, neuron differentiation and synaptic structure.

A meta-analysis of genome-wide association studies for neuroticism identifies novel loci, pathways and potential drug targets. Further analysis implicates specific brain regions and evaluates genetic overlap with other neuropsychiatric traits.

A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.

Analysis of paralog gene pairs using data from loss-of-function genetic screens in cancer cells identifies MAGOH and MAGOHB as reciprocal paralog dependencies across cancer types.

Multiregional analysis in 54 childhood cancers highlights four evolutionary patterns of intratumoral variation. Multiple patterns are often found in the same tumor, suggesting that tumors follow different evolutionary strategies concurrently.

Whole-genome sequencing of 303 Vibrio cholerae isolates taken from individuals and households over time in Bangladesh provides insight into the dynamics of cholera diversity and transmission in an endemic setting.

Integration of expression quantitative trait locus (eQTL) data from the Genotype-Tissue Expression project with genome-wide association study data shows that eQTLs are enriched for trait associations in disease-relevant tissues.

A transcriptome-wide association study identifies associations of genetically predicted gene expression with breast cancer risk. This analysis finds 48 candidate genes implicated in breast cancer susceptibility, including 14 at novel loci.

This study presents OncoTreat, a framework for the prioritization of compounds targeting mechanistic tumor dependencies in individual patients.

The authors describe the MiCEE complex, which comprises Mirlet7d ncRNA duplexes bound by C1D, the RNA exosome complex, and PRC2. MiCEE regulates bidirectionally transcribed loci and nucleolar organization.

MTF2 is shown to directly bind DNA and recruit PRC2 in mouse embryonic stem cells. MTF2 selectively binds regions with a high density of unmethylated CpGs in a context of reduced helix twist.

The authors show that the transcription factor Grainy head (Grh) is necessary and sufficient for opening of epithelial enhancers, but not for their activation. Grh is shown to function as a pioneer factor, displacing nucleosomes and paving the way for other transcription factors to activate enhancers.

The roles of of Gorab in the Golgi and in centriole structure and function can be separated mutationally in Drosophila. Complexed to Sas6 in the centriolar cartwheel, Gorab is essential for mitotic centriole duplication in the fly.

An integrated experimental-computational approach evaluates the impact of de novo missense mutations on protein–protein interactions. This interactome-based framework can be used to identify and prioritize disease-associated missense mutations.

A new set of functional annotations based on fine-mapped molecular quantitative trait loci from GTEx and BLUEPRINT consortium data are enriched for disease heritability across 41 diseases and complex traits.

Analysis of individuals with neurodevelopmental disorders (NDDs) with epilepsy identifies 33 genes with a significant excess of de novo variants. Comparison of rates of de novo variants between NDDs with or without epilepsy highlights differences between these phenotypic groups.

BayesTyper is a new probabilistic genotyping algorithm that offers superior sensitivity and accuracy relative to existing methods by using exact alignment of read k-mers to a graph representation of the reference and candidate variants.