Jing Hua Zhao

Jing Hua Zhao
Medical Research Council (UK) | mrc · MRC Epidemiology Unit

About

534
Publications
101,021
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
61,474
Citations
Citations since 2017
163 Research Items
32369 Citations
201720182019202020212022202301,0002,0003,0004,0005,000
201720182019202020212022202301,0002,0003,0004,0005,000
201720182019202020212022202301,0002,0003,0004,0005,000
201720182019202020212022202301,0002,0003,0004,0005,000

Publications

Publications (534)
Article
Full-text available
Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understa...
Article
Full-text available
Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensit...
Article
Full-text available
A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We fir...
Preprint
Full-text available
Lung function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry GWAS meta-analysis of lung function to date, comprising 580,869 participants, 1020 independent association signals identified 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. Th...
Article
Full-text available
BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our underst...
Article
Full-text available
Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use¹. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels², heart disease remains the leading cause of death worldwi...
Preprint
Full-text available
Genetic variants within nearly 1,000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. To expand our understanding of the underl...
Preprint
Full-text available
A major challenge of genome-wide association studies (GWAS) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We firs...
Preprint
Full-text available
We performed the largest genome-wide meta-analysis (GWAMA) (Max N=26,494) of the levels of 184 cardiovascular-related plasma protein levels to date and reported 592 independent loci (pQTL) associated with the level of at least one protein (1308 significant associations, median 6 per protein). We estimated that only between 8-37% of testable pQTL ov...
Preprint
Full-text available
Homeostatic control of blood glucose requires different physiological responses in the fasting and post-prandial states. We reasoned that glucose measurements under non-standardised conditions (random glucose, RG) may capture diverse glucoregulatory processes more effectively than previous genome-wide association studies (GWAS) of fasting glycaemia...
Preprint
Full-text available
Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quant...
Article
Full-text available
Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in...
Article
Full-text available
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10⁻⁸), of which 32 were in new BP-associated loci...
Preprint
Full-text available
Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization (MR) analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs o...
Article
Full-text available
Background Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes. Methods We constructed a polygenic risk score using a genome-wide assoc...
Article
Full-text available
Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the di...
Article
Full-text available
In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding...
Article
Full-text available
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association sign...
Article
Full-text available
The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene–smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. C...
Article
Full-text available
Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore,...
Article
Full-text available
Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individua...
Article
Full-text available
In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776...
Article
Full-text available
In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.
Article
Full-text available
C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 100...
Preprint
Full-text available
Birth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negat...
Article
Full-text available
High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insight...
Article
Full-text available
Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development p...
Article
Full-text available
Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understand...
Data
Summary of biological description for novel BP loci. Information summary of the nearest genes for blood pressure novel loci. (DOCX)
Data
Study design of SNV x alcohol interactions for BP. Schematic study design of the joint model of SNV main effect and SNV-alcohol consumption interaction; Blood pressure (BP) traits: systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP); Alcohol consumption was defined by two categories: (I) as current drinking...
Data
Description of participating studies. Study descriptions of discovery cohorts (Stage 1) and replication cohorts (Stage 2). (DOCX)
Data
Manhattan plots of combined Stage 1 and Stage 2 meta-analysis for SBP in current drinkers (A) and in light/heavy drinkers (B) in European ancestry. Novel loci are highlighted in blue. (TIF)
Data
Manhattan plots of combined Stage 1 and Stage 2 meta-analysis for SBP in current drinkers (A) and in light/heavy drinkers (B) in African ancestry. Novel loci are highlighted in blue. (TIF)
Data
Manhattan plots of combined Stage 1 and Stage 2 meta-analysis for DBP in current drinkers (A) and in light/heavy drinkers (B) in African ancestry. (TIF)
Data
Manhattan plots of combined Stage 1 and Stage 2 meta-analysis for SBP (A) and DBP (B) in current drinkers in Asian ancestry. (TIF)
Data
Protein-protein interactions network. In the figure, ellipses in black represent all novel genes; ellipses in red represent novel from EA; squares in blue represent potential novel findings from African ancestry; and triangles in black from correlated-meta. Labeled with A and B free-hand circles are proteins that have two connections, while labeled...
Data
Protein-protein interactions between tankyrase and beta-catenin. Tankyrase (from TNKS gene) and β-catenin (from CTNNB1 gene). (TIF)
Data
Wnt signaling KEGG pathway. TNKS interacts with CTNNB1. (TIF)
Data
Descriptive analyses for discovery data (Stage 1) in current drinkers. Characteristics of blood pressure (BP) in current drinkers (yes or no), within sub-sample of individuals with or without anti-hypertensive (BP Lowering) medications, and in combined samples; SBP, systolic BP; DBP, diastolic BP; MAP, mean arterial pressure; PP, pulse pressure; N,...
Data
Descriptive analyses for blood pressure (BP) stratified by alcohol consumption for discovery data (Stage 1). Characteristics of systolic BP and diastolic BP, after correcting for BP lowering medication and winsorizing observations. (XLSX)
Data
Descriptive analyses for replication data (Stage 2) in current drinkers. Characteristics of blood pressure (BP) within current drinkers (CURD: yes or no), and in alcohol combined samples; SBP, systolic BP; DBP, diastolic BP; MAP, mean arterial pressure; PP, pulse pressure; N, number of individuals; mean, mean levels; SD, standard deviation of mean;...
Data
Demographic statistics for replication data (Stage 2). N, Number of subjects; % Hypertensive, defined whether participants presented: (i) SBP ≥ 140 mm Hg, (ii) DBP ≥ 90 mm Hg, and/or (iii) taking anti-hypertensive medication; Mean, age mean; SD, standard deviation of mean; Min, minimum age; Max, maximum age. (XLSX)
Data
SNVs/genes associated with BP traits in European ancestry. Variants previously reported for blood pressure (BP) in genome-wide association studies. The most significant associated SNVs are shown per gene for each Blood Pressure (BP) trait and alcohol status. Abbreviations: Nb, order number based on genes; SNV, single nucleotide variant; Chr, chromo...
Data
SNVs/genes associated with BP traits in multi-ancestry meta-analysis in combined Stage 1 and Stage 2. Variants previously reported for blood pressure (BP) in genome-wide association studies. The most significant associated SNVs are shown per gene for each Blood Pressure (BP) trait and alcohol status. Abbreviations: Nb, order number based on genes;...
Data
Novel SNVs/genes associated with BP traits for eSNV/eQTL using GTEx. Target genes (Tissues and P-Values). Association findings from European Ancestry (novel) and correlated meta-analysis (novel variants). The annotation of variants was sourced from NCBI dbSNP build 138 (hg19) during the analyses and updated to dbSNP build 150 (hg38) for reporting r...
Data
Data analysis tools and databases. (DOCX)
Data
QQ plots for BP traits for light/heavy drinkers. Meta-analysis distributions of–log10 P-values of observed versus–log10 P-values expected (QQ plots) for light/heavy drinkers (1–7 drinks/week or ≥8 drinks/week) in European ancestry (A) and in African ancestry (B). (TIF)
Data
Manhattan plots of combined Stage 1 and Stage 2 meta-analysis for DBP in current drinkers (A) and in light/heavy drinkers (B) in European ancestry. Novel loci are highlighted in blue. (TIF)
Data
Manhattan plots of combined Stage 1 and Stage 2 meta-analysis for PP in current drinkers (A) and in light/heavy drinkers (B) in European ancestry. Novel loci are highlighted in blue. (TIF)
Data
Descriptive analyses for replication data (Stage 2) in light/heavy drinkers. Characteristics of blood pressure (BP) within light/heavy drinkers (LHD: 1–7 drinks/week or ≥8 drinks/week), and in alcohol combined samples; SBP, systolic BP; DBP, diastolic BP; MAP, mean arterial pressure; PP, pulse pressure; N, number of individuals; mean, mean levels;...
Data
Characteristics of each study and their genotype data for replication data (Stage 2). Study design, population-based or cohort-unrelated; Principal components used; Other covariates entered in the model; Genotyping platforms; Genotyping calling algorithm; Imputation reference panel; NCBI dbSNP build; Analysis software; Robust or model-based statist...
Data
Novel SNVs/ genes associated with BP traits in multi-ancestry and specific-ancestry meta-combined results. Top significant associated SNVs are shown per gene for each trait and alcohol exposure. (XLSX)
Data
SNVs/genes associated with BP traits in African ancestry. Variants previously reported for blood pressure (BP) in genome-wide association studies. The most significant associated SNVs are shown per gene for each Blood Pressure (BP) trait and alcohol status. Abbreviations: Nb, order number based on genes; SNV, single nucleotide variant; Chr, chromos...
Data
Regional association plots on 16q12. SNV x current drinker interaction for SBP (A), DBP (B), MAP (C) and PP (D) in European Ancestry. (TIF)
Data
Manhattan plots of combined Stage 1 and Stage 2 meta-analysis for MAP in current drinkers (A) and in light/heavy drinkers (B) in European ancestry. Novel loci are highlighted in blue. (TIF)
Data
Manhattan plots of combined Stage 1 and Stage 2 meta-analysis for PP in current drinkers (A) and in light/heavy drinkers (B) in African ancestry. Novel loci are highlighted in blue. (TIF)
Data
Manhattan plots of combined Stage 1 and Stage 2 meta-analysis for MAP (A) and PP (B) in current drinkers in Asian ancestry. (TIF)
Data
Descriptive analyses for discovery data (Stage 1) in light/heavy drinkers. Characteristics of blood pressure (BP) in light/heavy drinkers (1–7 drinks/week or ≥8 drinks/week), within sub-sample of individuals with or without anti-hypertensive (BP Lowering) medications, and in combined samples; SBP, systolic BP; DBP, diastolic BP; MAP, mean arterial...
Data
SNVs/genes associated with BP traits for regulatory features using HaploReg and RegulomeDB. Association findings from European Ancestry (novel), African Ancestry (potential) and correlated meta-analysis (novel variants). The annotation of variants was sourced from NCBI dbSNP build 138 (hg19) during the analyses and updated to dbSNP build 150 (hg38)...
Data
QQ plots for BP traits for current drinkers. Meta-analysis distributions of–log10 P-values of observed versus–log10 P-values expected (QQ plots) for current drinkers (yes/no) European ancestry (A) and in African ancestry (B). (TIF)