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De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

The authors survey community palaeontological databases, documenting their contributions to science as well as their vulnerabilities, and provide recommendations for the future of open science databases.

With rich, multi-layered baseline data and long-term follow-up through linkage, the HELIOS Study provides a resource to investigate the behavioural, environmental, genomic, and molecular factors impacting health in Asian populations.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Wearable data from 7,013 participants in the All of Us Research Program show that park accessibility across 53 US cities is positively associated with daily step counts, providing a mechanism for how urban green space can improve health.

Short linear motifs in disordered protein regions are involved numerous protein–protein interactions. Here, the authors find that the POLE2 subunit of human DNA polymerase ε acts as a motif binding protein capable to interact with a large number of protein molecules all containing NPF motifs.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Metal-metal bonds between metal cations are ubiquitous in coordination complexes, whereas similar bonding characteristics between non-metal and metal cations are not. Here, the authors report an X-ray crystal structure of a centrosymmetric complex [Ag(m-O₃SCF₃)₂{(4MePyNO)₂I}]₂ which features two unique I⁺–Ag⁺ bonds.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Variants in NOS1AP can cause monogenic nephrotic syndrome. Here, the authors show that disrupting the intergenic NOS1AP splice isoform that is more prevalent in podocytes leads to monogenic kidney disease responsive to RAAS inhibition.

The effect of sequence variants on phenotypes may depend on parental origin. Here, a method is developed that takes parental origin — the impact of which, to date, has largely been ignored — into account in genome-wide association studies. For 38,167 Icelanders genotyped, the parental origin of most alleles is determined; furthermore, a number of variants are found that show associations specific to parental origin, including three with type 2 diabetes.

The lymphatic system is a transport network that controls immune response and tissue fluid circulation in the body. Here the authors combine experiment and theory to reveal that developing lymphatic capillary networks exploit complementary branching strategies to optimize tissue coverage.

Around 1 in 136 pregnancies is lost due to a pathogenic small sequence variant genotype in the fetus.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Unnur Styrkarsdottir and Kari Stefansson and colleagues report the results of an expanded genome-wide association study for bone mineral density at the hip or the spine. New SNP associations were identified downstream of the SOST gene on 17q21, and in intron 1 of the MARK3 gene on 14q32.

Nature Computational Science asked a group of scientists to discuss strategies for increasing the presence of Black, Indigenous, People of Color (BIPOC) researchers in computational science, as well as the various considerations to be made for improving education and methods design.

Endometriosis is a common gynaecological disease but the underlying pathogenesis is poorly understood, however there is a strong familial component. Here the authors conduct a genome wide association study and identify a novel susceptibility locus that correlates with disease severity.

Elastic deformation of soft substrates occurs upon wetting, yet it is challenging to follow its dynamics at a microscale. Khattak et al. show that the force required to pull a droplet along a soft surface decreases monotonically as the film thickness decreases and explain the phenomenon using a scaling analysis.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources such as environmental amino acids, providing a potential therapeutic target.

Understanding the underlying pathophysiology of obesity can help prevent this condition. Here, the authors perform a GWAS of BMI in diverse ancestries, finding four missense variants in FRS3 that affect BMI.

Richard Houlston, Kari Hemminki and colleagues report a meta-analysis of genome-wide association studies of multiple myeloma and identify a variant in the CCDN1 gene that influences risk for developing a specific tumor karyotype with the t(11;14)(q13;q32) translocation.

Here, human genome-wide single-nucleotide polymorphism (SNP) data from more than 15,000 parent–offspring pairs have been used to construct the first recombination maps that are based on directly observed recombination events. The data reveal interesting differences between the sexes: for instance, in males recombination tends to shuffle exons, whereas in females it generates new combinations of nearby genes. Comparison of these maps with others also reveals population differences.

Methylation and mass cytometry investigations demonstrate the consequences of smoke exposure in humans at the single-cell level.

Most cyclic conjugated molecules, such as benzene, exhibit two sides. Möbius annulenes, however, with an odd number of 180° twists in their π system, are one-sided and violate the Hückel rule. Now, using a topological trick it is demonstrated that triply twisted systems are not particularly strained and probably easier to synthesize than singly twisted ones.

Augustine Kong, Kari Stefansson and colleagues report the discovery of common and low-frequency variants associated with genome-wide recombination rates. Most of the newly discovered variants exhibit differential effects on male and female recombination rates, and several map to genes with known roles in recombination, including RAD21L and MSH4.

Here the authors describe the discovery of a class of small molecule splicing modifiers which are orally bioavailable, cross the blood-brain barrier, and lower levels of huntingtin in a mouse model of Huntington’s disease (HD).

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Genome-wide association analyses of migraine and its subtypes identify new susceptibility loci, including rare variants with large effects implicating PRRT2, SCN11A and KCNK5.

The causality and functional roles of disease-associated variants revealed by genome-wide association studies (GWAS) are mostly unexplored. Here the authors identify putative causal variants in multiple myeloma and find their association with gene expression and chromatin accessibility.

Daniel Gudbjartsson, Kari Stefansson and colleagues assess the effect of variants associated with mean fasting glucose levels on the variance in fasting glucose levels. They find that variants that increase both the levels and variance of fasting glucose increase type 2 diabetes risk, whereas those that increase the levels but reduce the variance do not.

High-resolution imaging and biochemical approaches provide insights into the structural and functional changes in the host cell nucleolus upon canine parvovirus infection.

Antila et al. show that brain amyloid-β load is not significantly affected by sustained dural lymphatic vessel atrophy or hyperplasia induced by lymphangiogenic growth factor manipulation in two mouse models of Alzheimer’s disease.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Maternal genome-wide analyses identify variants associated with gestational duration and preterm delivery. Maternal alleles positively associated with gestational duration exhibit negative fetal effects on birth weight, likely reflecting antagonistic pleiotropy.

Kari Stefansson and colleagues report the whole-genome sequencing of 2,636 individuals from Iceland to a median of 20× coverage, providing a valuable genomic resource for this population isolate. They characterize patterns of genetic variation and population structure and demonstrate the usefulness of this resource for genetic discovery for several disease phenotypes.

Ingileif Jonsdottir, Björn Nilsson, Kari Stefansson and colleagues perform a genome-wide association study for immunoglobulin levels in Icelandic and Swedish cohorts. They find 38 new variants associated with IgA, IgG, IgM or composite immunoglobulin traits and identify candidate genes underlying the regulation of immunoglobulin levels.

To measure selection on variants, whole-genome sequencing of approximately 150,000 individuals from the UK Biobank is used to rank sequence variants by their level of depletion.

The authors present a multiomics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits in Hispanic/Latino populations. They demonstrate how integrating GWAS with omics characterization can advance precision medicine.

Whole-genome sequencing of monozygotic twins, along with their parents, spouses and children, identifies postzygotic mutations present in the somatic tissue of one twin, but not the other, and characterizes differences in the number and timing of these mutations.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

Genome-wide analyses identify 27 loci associated with attention-deficit hyperactivity disorder and provide insights into its genetic architecture in relation to other psychiatric disorders and cognitive traits.

Warming temperatures and interactions between plants are the main drivers of changes in Arctic plant communities in response to climate change, and there is no evidence of overall biotic homogenization.

Trans-ethnic analyses of exome array data identify new risk loci for type 2 diabetes. Fine-mapping analyses using genome-wide association data show that the index coding variants represent the likely causal variants at only a subset of these loci.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Two hundred and eighty-five methylomes and 11,617 transcriptomes from peripheral blood samples with parent-of-origin-phased haplotypes produce a new map of imprinted methylation and gene expression patterns across the human genome.