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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
A multi-ancestry genome-wide association study meta-analysis, combined with transcriptome- and methylome-wide association analyses, identifies risk loci associated with colorectal cancer. Credible effector genes and their target tissues are also highlighted, showing that over a third probably act outside the colonic mucosa.
Journal Article
Recent Advances in Understanding Multi-scale Climate Variability of the Asian Monsoon
Studies of the multi-scale climate variability of the Asian monsoon are essential to an advanced understanding of the physical processes of the global climate system. In this paper, the progress achieved in this field is systematically reviewed, with a focus on the past several years. The achievements are summarized into the following topics: (1) the onset of the South China Sea summer monsoon; (2) the East Asian summer monsoon; (3) the East Asian winter monsoon; and (4) the Indian summer monsoon. Specifically, new results are highlighted, including the advanced or delayed local monsoon onset tending to be synchronized over the Arabian Sea, Bay of Bengal, Indochina Peninsula, and South China Sea; the basic features of the record-breaking mei-yu in 2020, which have been extensively investigated with an emphasis on the role of multi-scale processes; the recovery of the East Asian winter monsoon intensity after the early 2000s in the presence of continuing greenhouse gas emissions, which is believed to have been dominated by internal climate variability (mostly the Arctic Oscillation); and the accelerated warming over South Asia, which exceeded the tropical Indian Ocean warming, is considered to be the main driver of the Indian summer monsoon rainfall recovery since 1999. A brief summary is provided in the final section along with some further discussion on future research directions regarding our understanding of the Asian monsoon variability.
Journal Article
East Asian Voices of Resistance Against Racism in Music
The negative racialization of East Asian musicians in Western classical music manifests through tropes of othering such as \"Yellow Peril,\" Orientalism, and various harmful stereotypes. This volume centers East Asian voices - in collaboration with our allies - as narrators of our own racialized experiences in music. Featuring eleven contributions, in a mixture of tone that is academic and personal or reflective - thus deliberately disrupting conventional linguistic norms - the volume brings together our voices in a creative act of resistance against racism in music, and in solidarity with activism that targets inequalities in the arts more broadly. The volume is, to our knowledge, the first of its kind. Intended for musicians and artists, academics and students, it will dynamize topical conversations circling around issues of equality, diversity and inclusion so as to contribute towards positive change.
eBook
Recent Progress in Studies of the Variabilities and Mechanisms of the East Asian Monsoon in a Changing Climate
Located in a monsoon domain, East Asia suffers devastating natural hazards induced by anomalous monsoon behaviors. East Asian monsoon (EAM) research has traditionally been a high priority for the Chinese climate community and is particularly challenging in a changing climate where the global mean temperature has been rising. Recent advances in studies of the variabilities and mechanisms of the EAM are reviewed in this paper, focusing on the interannual to interdecadal time scales. Some new results have been achieved in understanding the behaviors of the EAM, such as the evolution of the East Asian summer monsoon (EASM), including both its onset and withdrawal over the South China Sea, the changes in the northern boundary activity of the EASM, or the transitional climate zone in East Asia, and the cycle of the EASM and the East Asian winter monsoon and their linkages. In addition, understanding of the mechanism of the EAM variability has improved in several aspects, including the impacts of different types of ENSO on the EAM, the impacts from the Indian Ocean and Atlantic Ocean, and the roles of mid- to high-latitude processes. Finally, some scientific issues regarding our understanding of the EAM are proposed for future investigation.
Journal Article
A pangenome reference of 36 Chinese populations
Human genomics is witnessing an ongoing paradigm shift from a single reference sequence to a pangenome form, but populations of Asian ancestry are underrepresented. Here we present data from the first phase of the Chinese Pangenome Consortium, including a collection of 116 high-quality and haplotype-phased de novo assemblies based on 58 core samples representing 36 minority Chinese ethnic groups. With an average 30.65× high-fidelity long-read sequence coverage, an average contiguity N50 of more than 35.63 megabases and an average total size of 3.01 gigabases, the CPC core assemblies add 189 million base pairs of euchromatic polymorphic sequences and 1,367 protein-coding gene duplications to GRCh38. We identified 15.9 million small variants and 78,072 structural variants, of which 5.9 million small variants and 34,223 structural variants were not reported in a recently released pangenome reference
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. The Chinese Pangenome Consortium data demonstrate a remarkable increase in the discovery of novel and missing sequences when individuals are included from underrepresented minority ethnic groups. The missing reference sequences were enriched with archaic-derived alleles and genes that confer essential functions related to keratinization, response to ultraviolet radiation, DNA repair, immunological responses and lifespan, implying great potential for shedding new light on human evolution and recovering missing heritability in complex disease mapping.
A study reports data from the first phase of the Chinese Pangenome Consortium including 116 de novo assemblies from 58 core samples representing 36 minority Chinese ethnic groups.
Journal Article