Wendy K. Chung

Bio: Wendy K. Chung is an academic researcher from Columbia University. The author has contributed to research in topics: Population & Genome-wide association study. The author has an hindex of 13, co-authored 40 publications receiving 1567 citations. Previous affiliations of Wendy K. Chung include Columbia University Medical Center & New York University.

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

Abstract: Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.

Precision Medicine in Diabetes: A Consensus Report From the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Abstract: The convergence of advances in medical science, human biology, data science, and technology has enabled the generation of new insights into the phenotype known as "diabetes." Increased knowledge of this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence, and how best practice in treatment varies between populations. In parallel, focus has been placed on the development of tools for the application of precision medicine to numerous conditions. This Consensus Report presents the American Diabetes Association (ADA) Precision Medicine in Diabetes Initiative in partnership with the European Association for the Study of Diabetes (EASD), including its mission, the current state of the field, and prospects for the future. Expert opinions are presented on areas of precision diagnostics and precision therapeutics (including prevention and treatment), and key barriers to and opportunities for implementation of precision diabetes medicine, with better care and outcomes around the globe, are highlighted. Cases where precision diagnosis is already feasible and effective (i.e., monogenic forms of diabetes) are presented, while the major hurdles to the global implementation of precision diagnosis of complex forms of diabetes are discussed. The situation is similar for precision therapeutics, in which the appropriate therapy will often change over time owing to the manner in which diabetes evolves within individual patients. This Consensus Report describes a foundation for precision diabetes medicine, while highlighting what remains to be done to realize its potential. This, combined with a subsequent, detailed evidence-based review (due 2022), will provide a roadmap for precision medicine in diabetes that helps improve the quality of life for all those with diabetes.

Congenital diaphragmatic hernias: from genes to mechanisms to therapies.

Abstract: Congenital diaphragmatic hernias (CDHs) and structural anomalies of the diaphragm are a common class of congenital birth defects that are associated with significant morbidity and mortality due to associated pulmonary hypoplasia, pulmonary hypertension and heart failure. In ∼30% of CDH patients, genomic analyses have identified a range of genetic defects, including chromosomal anomalies, copy number variants and sequence variants. The affected genes identified in CDH patients include transcription factors, such as GATA4, ZFPM2, NR2F2 and WT1, and signaling pathway components, including members of the retinoic acid pathway. Mutations in these genes affect diaphragm development and can have pleiotropic effects on pulmonary and cardiac development. New therapies, including fetal endoscopic tracheal occlusion and prenatal transplacental fetal treatments, aim to normalize lung development and pulmonary vascular tone to prevent and treat lung hypoplasia and pulmonary hypertension, respectively. Studies of the association between particular genetic mutations and clinical outcomes should allow us to better understand the origin of this birth defect and to improve our ability to predict and identify patients most likely to benefit from specialized treatment strategies.

Precision medicine in diabetes : a Consensus Report from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Abstract: The convergence of advances in medical science, human biology, data science and technology has enabled the generation of new insights into the phenotype known as ‘diabetes’ Increased knowledge of this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence and how best practice in treatment varies between populations In parallel, focus has been placed on the development of tools for the application of precision medicine to numerous conditions This Consensus Report presents the American Diabetes Association (ADA) Precision Medicine in Diabetes Initiative in partnership with the European Association for the Study of Diabetes (EASD), including its mission, the current state of the field and prospects for the future Expert opinions are presented on areas of precision diagnostics and precision therapeutics (including prevention and treatment) and key barriers to and opportunities for implementation of precision diabetes medicine, with better care and outcomes around the globe, are highlighted Cases where precision diagnosis is already feasible and effective (ie monogenic forms of diabetes) are presented, while the major hurdles to the global implementation of precision diagnosis of complex forms of diabetes are discussed The situation is similar for precision therapeutics, in which the appropriate therapy will often change over time owing to the manner in which diabetes evolves within individual patients This Consensus Report describes a foundation for precision diabetes medicine, while highlighting what remains to be done to realise its potential This, combined with a subsequent, detailed evidence-based review (due 2022), will provide a roadmap for precision medicine in diabetes that helps improve the quality of life for all those with diabetes

Constructing Grounded Theory: A Practical Guide through Qualitative Analysis

Abstract: การวจยเชงคณภาพ เปนเครองมอสำคญอยางหนงสำหรบทำความเขาใจสงคมและพฤตกรรมมนษย การวจยแบบการสรางทฤษฎจากขอมล กเปนหนงในหลายระเบยบวธการวจยเชงคณภาพทกำลงไดรบความสนใจ และเปนทนยมเพมสงขนเรอยๆ จากนกวชาการ และนกวจยในสาขาสงคมศาสตร และศาสตรอนๆ เชน พฤตกรรมศาสตร สงคมวทยา สาธารณสขศาสตร พยาบาลศาสตร จตวทยาสงคม ศกษาศาสตร รฐศาสตร และสารสนเทศศกษา ดงนน หนงสอเรอง “ConstructingGrounded Theory: A Practical Guide through Qualitative Analysis” หรอ “การสรางทฤษฎจากขอมล:แนวทางการปฏบตผานการวเคราะหเชงคณภาพ” จะชวยใหผอานมความรความเขาใจถงพฒนาการของปฏบตการวจยแบบสรางทฤษฎจากขอมล ตลอดจนแนวทาง และกระบวนการปฏบตการวจยอยางเปนระบบ จงเปนหนงสอทควรคาแกการอานโดยเฉพาะนกวจยรนใหม เพอเปนแนวทางในการนำความรความเขาใจไประยกตในงานวจยของตน อกทงนกวจยผเชยวชาญสามารถอานเพอขยายมโนทศนดานวจยใหกวางขวางขน

Ensembl 2021

Abstract: The Ensembl project (https://www ensembl org) annotates genomes and disseminates genomic data for vertebrate species We create detailed and comprehensive annotation of gene structures, regulatory elements and variants, and enable comparative genomics by inferring the evolutionary history of genes and genomes Our integrated genomic data are made available in a variety of ways, including genome browsers, search interfaces, specialist tools such as the Ensembl Variant Effect Predictor, download files and programmatic interfaces Here, we present recent Ensembl developments including two new website portals Ensembl Rapid Release (http://rapid ensembl org) is designed to provide core tools and services for genomes as soon as possible and has been deployed to support large biodiversity sequencing projects Our SARS-CoV-2 genome browser (https://covid-19 ensembl org) integrates our own annotation with publicly available genomic data from numerous sources to facilitate the use of genomics in the international scientific response to the COVID-19 pandemic We also report on other updates to our annotation resources, tools and services All Ensembl data and software are freely available without restriction

Pan-cancer whole-genome analyses of metastatic solid tumours

Abstract: Metastatic cancer is a major cause of death and is associated with poor treatment efficacy. A better understanding of the characteristics of late-stage cancer is required to help adapt personalized treatments, reduce overtreatment and improve outcomes. Here we describe the largest, to our knowledge, pan-cancer study of metastatic solid tumour genomes, including whole-genome sequencing data for 2,520 pairs of tumour and normal tissue, analysed at median depths of 106× and 38×, respectively, and surveying more than 70 million somatic variants. The characteristic mutations of metastatic lesions varied widely, with mutations that reflect those of the primary tumour types, and with high rates of whole-genome duplication events (56%). Individual metastatic lesions were relatively homogeneous, with the vast majority (96%) of driver mutations being clonal and up to 80% of tumour-suppressor genes being inactivated bi-allelically by different mutational mechanisms. Although metastatic tumour genomes showed similar mutational landscape and driver genes to primary tumours, we find characteristics that could contribute to responsiveness to therapy or resistance in individual patients. We implement an approach for the review of clinically relevant associations and their potential for actionability. For 62% of patients, we identify genetic variants that may be used to stratify patients towards therapies that either have been approved or are in clinical trials. This demonstrates the importance of comprehensive genomic tumour profiling for precision medicine in cancer. The mutational landscape of metastatic cancer genomes is analysed in a large-scale, pan-cancer study of metastatic solid tumours that includes whole-genome sequencing of 2,520 tumour–normal tissue pairs.