Reviews & Analysis

Recent advances in Hi-C, single-cell imaging and functional genetic studies warrant discussion on the functional relevance of topologically associating domains (TADs) and other classes of chromatin domains.

A Perspective on the future of agricultural genebank collections discusses how the use of molecular passport data can help facilitate genomic selection and accelerate crop breeding.

This Perspective discusses how best to interpret pLI, a measure widely used to identify genes that are intolerant to a single copy of a truncating mutation, by relating this and related measures to the underlying population-genetic theory.

Transcriptome-wide association studies (TWAS) prioritize candidate causal genes at GWAS loci. This Perspective discusses the challenges to TWAS analysis, caveats to interpretation of results and opportunities for improvements to this class of methods.

This Perspective discusses scientific and ethical considerations regarding the clinical use of polygenic risk scores, highlighting the pressing need to diversify cohorts for genetic studies beyond European-ancestry populations.

Single-cell and single-molecule epigenomics to uncover genome regulation at unprecedented resolution.

This perspective presents a primer on deep learning applications for the genomics field. It includes a general guide for how to use deep learning and describes the current tools and resources that are available to the community.

Mitochondrial variants are important to consider when analyzing the genetics of various metabolic or age-related diseases. These mtDNA variants can influence the penetrance of a phenotype or interact differentially with nuclear DNA variants.

This proposal calls for the initiation of national population-screening programs to identify carriers of cancer gene mutations for long-term, large-scale analysis of longitudinal clinical data to aid in prevention and early detection of disease.

This Perspective describes different study designs for the genetic analyses of large-scale cohorts, using Dutch cohorts as primary examples, and discusses lessons learned as well as recommendations for future cohort studies.

Wayne Powell and colleagues compare the different tools and approaches used by the plant breeding community versus the animal breeding community for crop and livestock improvement. They argue that the two disciplines can be united via adoption of genomic selection along with the exchange of resources and techniques between the two areas.

Jian Yang and colleagues explore the uses and abuses of heritability estimates derived from pedigrees and from GWAS SNPs and make recommendations for best practice in future applications of SNP-based heritability.

Carrolee Barlow, J. William Langston, Birgitt Schüle and colleagues review the current classification of parkinsonian disorders. They propose the term 'multisystem Lewy body disease' to encompass three genetic subtypes of Parkinson's disease and distinguish this from other non–Lewy body parkinsonian disorders.

Jason Lieb and Sebastian Pott review the identification and composition of super-enhancers and ask whether super-enhancers are a new, conceptually distinct regulatory entity.

Alkes Price, Peter Visscher and colleagues provide recommendations on the application of mixed-linear-model association methods across a range of study designs.

Jake Gratten and colleagues discuss challenges in interpreting the role of de novo mutations in neuropsychiatric and other complex diseases. They argue that the burden of proof for causality for a single de novo mutation must be set high and that curation of de novo mutations and their associated phenotypes in databases will be critical for the robust interpretation of exome sequencing studies.

Shamil Sunyaev and colleagues present exome sequencing methods and their applications in studies to identify the genetic basis of human complex traits. They include analyses of the whole-exome sequences of 438 individuals from across several studies.