A genomic mutational constraint map using variation in 76,156 human genomes

S Chen, LC Francioli, JK Goodrich, RL Collins, M Kanai… - Nature, 2024 - nature.com
The depletion of disruptive variation caused by purifying natural selection (constraint) has
been widely used to investigate protein-coding genes underlying human disorders,,–, but …

Promoting equity in polygenic risk assessment through global collaboration

IJ Kullo - Nature Genetics, 2024 - nature.com
The long delay before genomic technologies become available in low-and middle-income
countries is a concern from both scientific and ethical standpoints. Polygenic risk scores …

High-coverage nanopore sequencing of samples from the 1000 Genomes Project to build a comprehensive catalog of human genetic variation

JA Gustafson, SB Gibson, N Damaraju… - Genome …, 2024 - genome.cshlp.org
Fewer than half of individuals with a suspected Mendelian or monogenic condition receive a
precise molecular diagnosis after comprehensive clinical genetic testing. Improvements in …

Genetic and molecular architecture of complex traits

T Lappalainen, YI Li, S Ramachandran, A Gusev - Cell, 2024 - cell.com
Human genetics has emerged as one of the most dynamic areas of biology, with a
broadening societal impact. In this review, we discuss recent achievements, ongoing efforts …

Recurrent evolution and selection shape structural diversity at the amylase locus

D Bolognini, A Halgren, RN Lou, A Raveane, JL Rocha… - Nature, 2024 - nature.com
The adoption of agriculture triggered a rapid shift towards starch-rich diets in human
populations. Amylase genes facilitate starch digestion, and increased amylase copy number …

A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus

D Pellerin, GF Del Gobbo, M Couse, E Dolzhenko… - Nature …, 2024 - nature.com
The factors driving or preventing pathological expansion of tandem repeats remain largely
unknown. Here, we assessed the FGF14 (GAA)·(TTC) repeat locus in 2,530 individuals by …

Genes with differential expression across ancestries are enriched in ancestry-specific disease effects likely due to gene-by-environment interactions

J Wang, Z Zhang, Z Lu, N Mancuso, S Gazal - The American Journal of …, 2024 - cell.com
Multi-ancestry genome-wide association studies (GWASs) have highlighted the existence of
variants with ancestry-specific effect sizes. Understanding where and why these ancestry …

CHARR efficiently estimates contamination from DNA sequencing data

W Lu, LD Gauthier, T Poterba, E Giacopuzzi… - The American Journal of …, 2023 - cell.com
DNA sample contamination is a major issue in clinical and research applications of whole-
genome and-exome sequencing. Even modest levels of contamination can substantially …

Genetic architecture and socio-environmental risk factors for major depressive disorder in Nepal

KW Choi, JD Tubbs, YH Lee, Y He, K Tsuo… - Psychological …, 2024 - cambridge.org
BackgroundMajor depressive disorder (MDD) is the leading cause of disability globally, with
moderate heritability and well-established socio-environmental risk factors. Genetic studies …

Individuals with JAK1 variants are affected by syndromic features encompassing autoimmunity, atopy, colitis, and dermatitis

ME Horesh, M Martin-Fernandez, C Gruber… - Journal of Experimental …, 2024 - rupress.org
Inborn errors of immunity lead to autoimmunity, inflammation, allergy, infection, and/or
malignancy. Disease-causing JAK1 gain-of-function (GoF) mutations are considered …