Global Biobank Meta-analysis Initiative:Powering genetic discovery across human disease

Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)—a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.</p

Sources of evolution of the Japan Air Self-Defense Force's strategy

The Japan Air Self-Defense Force's (JASDF) activities, training, and weapons after the first decade of this century seem to deviate from the exclusively defense-oriented policy. This thesis investigates what is driving the evolution of JASDF's strategy behind this behavior and what is the most influential driver of that evolving strategy. This thesis first examines the JASDF's strategic changes in terms of ends, ways, and means, and assesses these changes through the concepts of defensive defense and offensive defense to illuminate the JASDF's strategy. Then, this thesis analyzes four possible drivers of the JASDF's strategic evolution: the People's Liberation Army's (PLA) air power, the North Korean threat, the conservative swing of Japanese domestic politics, and the offensive nature of the air strategy. This thesis argues that the JASDF's strategy has evolved from the defensive defense strategy to the offensive defense strategy after the early 2000s. In addition, even though the evolution of the JASDF's strategy is a combined result of the four independent variables, the strongest driver is the modernization of the PLA's air power. Therefore, the improvement of the relationship between Japan and China is the most important factor in curtailing an arms race in Northeast Asia.http://archive.org/details/sourcesofevoluti1094551559Captain, Republic of Korea Air ForceApproved for public release; distribution is unlimited

Uncovering associations between pre-existing conditions and COVID-19 Severity: A polygenic risk score approach across three large biobanks.

OBJECTIVE: To overcome the limitations associated with the collection and curation of COVID-19 outcome data in biobanks, this study proposes the use of polygenic risk scores (PRS) as reliable proxies of COVID-19 severity across three large biobanks: the Michigan Genomics Initiative (MGI), UK Biobank (UKB), and NIH All of Us. The goal is to identify associations between pre-existing conditions and COVID-19 severity. METHODS: Drawing on a sample of more than 500,000 individuals from the three biobanks, we conducted a phenome-wide association study (PheWAS) to identify associations between a PRS for COVID-19 severity, derived from a genome-wide association study on COVID-19 hospitalization, and clinical pre-existing, pre-pandemic phenotypes. We performed cohort-specific PRS PheWAS and a subsequent fixed-effects meta-analysis. RESULTS: The current study uncovered 23 pre-existing conditions significantly associated with the COVID-19 severity PRS in cohort-specific analyses, of which 21 were observed in the UKB cohort and two in the MGI cohort. The meta-analysis yielded 27 significant phenotypes predominantly related to obesity, metabolic disorders, and cardiovascular conditions. After adjusting for body mass index, several clinical phenotypes, such as hypercholesterolemia and gastrointestinal disorders, remained associated with an increased risk of hospitalization following COVID-19 infection. CONCLUSION: By employing PRS as a proxy for COVID-19 severity, we corroborated known risk factors and identified novel associations between pre-existing clinical phenotypes and COVID-19 severity. Our study highlights the potential value of using PRS when actual outcome data may be limited or inadequate for robust analyses

Uncovering associations between pre-existing conditions and COVID-19 Severity: A polygenic risk score approach across three large biobanks.

OBJECTIVE: To overcome the limitations associated with the collection and curation of COVID-19 outcome data in biobanks, this study proposes the use of polygenic risk scores (PRS) as reliable proxies of COVID-19 severity across three large biobanks: the Michigan Genomics Initiative (MGI), UK Biobank (UKB), and NIH All of Us. The goal is to identify associations between pre-existing conditions and COVID-19 severity. METHODS: Drawing on a sample of more than 500,000 individuals from the three biobanks, we conducted a phenome-wide association study (PheWAS) to identify associations between a PRS for COVID-19 severity, derived from a genome-wide association study on COVID-19 hospitalization, and clinical pre-existing, pre-pandemic phenotypes. We performed cohort-specific PRS PheWAS and a subsequent fixed-effects meta-analysis. RESULTS: The current study uncovered 23 pre-existing conditions significantly associated with the COVID-19 severity PRS in cohort-specific analyses, of which 21 were observed in the UKB cohort and two in the MGI cohort. The meta-analysis yielded 27 significant phenotypes predominantly related to obesity, metabolic disorders, and cardiovascular conditions. After adjusting for body mass index, several clinical phenotypes, such as hypercholesterolemia and gastrointestinal disorders, remained associated with an increased risk of hospitalization following COVID-19 infection. CONCLUSION: By employing PRS as a proxy for COVID-19 severity, we corroborated known risk factors and identified novel associations between pre-existing clinical phenotypes and COVID-19 severity. Our study highlights the potential value of using PRS when actual outcome data may be limited or inadequate for robust analyses

Uncovering associations between pre-existing conditions and COVID-19 Severity: A polygenic risk score approach across three large biobanks.

ObjectiveTo overcome the limitations associated with the collection and curation of COVID-19 outcome data in biobanks, this study proposes the use of polygenic risk scores (PRS) as reliable proxies of COVID-19 severity across three large biobanks: the Michigan Genomics Initiative (MGI), UK Biobank (UKB), and NIH All of Us. The goal is to identify associations between pre-existing conditions and COVID-19 severity.MethodsDrawing on a sample of more than 500,000 individuals from the three biobanks, we conducted a phenome-wide association study (PheWAS) to identify associations between a PRS for COVID-19 severity, derived from a genome-wide association study on COVID-19 hospitalization, and clinical pre-existing, pre-pandemic phenotypes. We performed cohort-specific PRS PheWAS and a subsequent fixed-effects meta-analysis.ResultsThe current study uncovered 23 pre-existing conditions significantly associated with the COVID-19 severity PRS in cohort-specific analyses, of which 21 were observed in the UKB cohort and two in the MGI cohort. The meta-analysis yielded 27 significant phenotypes predominantly related to obesity, metabolic disorders, and cardiovascular conditions. After adjusting for body mass index, several clinical phenotypes, such as hypercholesterolemia and gastrointestinal disorders, remained associated with an increased risk of hospitalization following COVID-19 infection.ConclusionBy employing PRS as a proxy for COVID-19 severity, we corroborated known risk factors and identified novel associations between pre-existing clinical phenotypes and COVID-19 severity. Our study highlights the potential value of using PRS when actual outcome data may be limited or inadequate for robust analyses

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausibility of distinct influences of both sleep duration extremes in cardiovascular health. With several of our loci reflecting specificity towards population background or sex, our discovery sheds light on the importance of embracing granularity when addressing heterogeneity entangled in gene-environment interactions, and in therapeutic design approaches for blood pressure management

Global Biobank Meta-analysis Initiative: Powering genetic discovery across human disease

Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)—a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits

Global Biobank Meta-analysis Initiative: Powering genetic discovery across human disease

Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits

Global Biobank Meta-analysis Initiative: Powering genetic discovery across human disease

Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)—a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.</p