The path to healthy ageing in China: a Peking University-Lancet Commission.

Unlabelled: Around the world, populations are ageing at a faster pace than in the past and this demographic transition will have impacts on all aspects of societies. In May 2020, the UN General Assembly declared 2021–2030 the Decade of Healthy Ageing, highlighting the importance for policymakers across the world to focus policy on improving the lives of older people, both today and in the future. While rapid population ageing poses challenges, China’s rapid economic growth over the last forty years has created space for policy to assist older persons and families in their efforts to improve health and well-being at older ages.

Expectations and blind spots for structural variation detection from long-read assemblies and short-read genome sequencing technologies.

Virtually all genome sequencing efforts in national biobanks, complex and Mendelian disease programs, and medical genetic initiatives are reliant upon short-read whole-genome sequencing (srWGS), which presents challenges for the detection of structural variants (SVs) relative to emerging long-read WGS (lrWGS) technologies. Given this ubiquity of srWGS in large-scale genomics initiatives, we sought to establish expectations for routine SV detection from this data type by comparison with lrWGS assembly, as well as to quantify the genomic properties and added value of SVs uniquely accessible to each technology. Analyses from the Human Genome Structural Variation Consortium (HGSVC) of three families captured ~11,000 SVs per genome from srWGS and ~25,000 SVs per genome from lrWGS assembly.

De novo structural mutation rates and gamete-of-origin biases revealed through genome sequencing of 2,396 families.

Each human genome includes de novo mutations that arose during gametogenesis. While these germline mutations represent a fundamental source of new genetic diversity, they can also create deleterious alleles that impact fitness. Whereas the rate and patterns of point mutations in the human germline are now well understood, far less is known about the frequency and features that impact de novo structural variants (dnSVs).

Functional annotation of rare structural variation in the human brain.

Structural variants (SVs) contribute to many disorders, yet, functionally annotating them remains a major challenge. Here, we integrate SVs with RNA-sequencing from human post-mortem brains to quantify their dosage and regulatory effects. We show that genic and regulatory SVs exist at significantly lower frequencies than intergenic SVs.

A structural variation reference for medical and population genetics.

Structural variants (SVs) rearrange large segments of DNA and can have profound consequences in evolution and human disease. As national biobanks, disease-association studies, and clinical genetic testing have grown increasingly reliant on genome sequencing, population references such as the Genome Aggregation Database (gnomAD) have become integral in the interpretation of single-nucleotide variants (SNVs). However, there are no reference maps of SVs from high-coverage genome sequencing comparable to those for SNVs.

A Balanced Translocation in Kallmann Syndrome Implicates a Long Noncoding RNA, RMST, as a GnRH Neuronal Regulator.

Context: Kallmann syndrome (KS) is a rare, genetically heterogeneous Mendelian disorder. Structural defects in KS patients have helped define the genetic architecture of gonadotropin-releasing hormone (GnRH) neuronal development in this condition.

Objective: Examine the functional role a novel structural defect affecting a long noncoding RNA (lncRNA), RMST, found in a KS patient.

Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder.

Whole-genome sequencing (WGS) has facilitated the first genome-wide evaluations of the contribution of de novo noncoding mutations to complex disorders. Using WGS, we identified 255,106 de novo mutations among sample genomes from members of 1902 quartet families in which one child, but not a sibling or their parents, was affected by autism spectrum disorder (ASD). In contrast to coding mutations, no noncoding functional annotation category, analyzed in isolation, was significantly associated with ASD.

Environmental governance in China: Interactions between the state and "nonstate actors".

In the West, limited government capacity to solve environmental problems has triggered the rise of a variety of "nonstate actors" to supplement government efforts or provide alternative mechanisms for addressing environmental issues. How does this development - along with our efforts to understand it - map onto environmental governance processes in China? China's efforts to address environmental issues reflect institutionalized governance processes that differ from parallel western processes in ways that have major consequences for domestic environmental governance practices and the governance of China "going abroad." China's governance processes blur the distinction between the state and other actors; the "shadow of the state" is a major factor in all efforts to address environmental issues.

An analytical framework for whole-genome sequence association studies and its implications for autism spectrum disorder.

Genomic association studies of common or rare protein-coding variation have established robust statistical approaches to account for multiple testing. Here we present a comparable framework to evaluate rare and de novo noncoding single-nucleotide variants, insertion/deletions, and all classes of structural variation from whole-genome sequencing (WGS). Integrating genomic annotations at the level of nucleotides, genes, and regulatory regions, we define 51,801 annotation categories.

Potential involvement of the interleukin-18 pathway in schizophrenia.

Objective: Accumulating evidence implicates inflammatory cytokines in the development of psychiatric disorders, including schizophrenia (SZ). IL-18 is one of cytokines that plays a crucial role in immune response and neurodevelopment. We aimed to investigate potential genetic alterations of the cytokine system underpinning SZ.

Family-based tests applied to extended pedigrees identify rare variants related to hypertension.

The application of family-based tests to whole-genome sequenced data provides a new window on the role of rare variant alleles in the etiology of disease. By applying family-based tests to these data, we can now identify rare variants associated with disease. Approaches for common variants, by contrast, require large sample sizes for power, and are powerless when faced with rare variants.

New insights into the genetic mechanism of IQ in autism spectrum disorders.

Autism spectrum disorders (ASD) comprise a number of underlying sub-types with various symptoms and presumably different genetic causes. One important difference between these sub-phenotypes is IQ. Some forms of ASD such as Asperger's have relatively intact intelligence while the majority does not.