Publications
15 results found
Hahn J, Bressler J, Domingo-Relloso A, et al., 2023, DNA methylation analysis is used to identify novel genetic loci associated with circulating fibrinogen levels in blood, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 21, Pages: 1135-1147, ISSN: 1538-7933
Huang J, Gill D, Zuber V, et al., 2023, Circulatory proteins relate cardiovascular disease to cognitive performance: a Mendelian randomisation study, Frontiers in Genetics, Vol: 14, Pages: 1-11, ISSN: 1664-8021
Background and objectives: Mechanistic research suggests synergistic effects of cardiovascular disease (CVD) and dementia pathologies on cognitive decline. Interventions targeting proteins relevant to shared mechanisms underlying CVD and dementia could also be used for the prevention of cognitive impairment.Methods: We applied Mendelian randomisation (MR) and colocalization analysis to investigate the causal relationships of 90 CVD-related proteins measured by the Olink CVD I panel with cognitive traits. Genetic instruments for circulatory protein concentrations were obtained using a meta-analysis of genome-wide association studies (GWAS) from the SCALLOP consortium (N = 17,747) based on three sets of criteria: 1) protein quantitative trait loci (pQTL); 2) cis-pQTL (pQTL within ±500 kb from the coding gene); and 3) brain-specific cis-expression QTL (cis-eQTL) which accounts for coding gene expression based on GTEx8. Genetic associations of cognitive performance were obtained from GWAS for either: 1) general cognitive function constructed using Principal Component Analysis (N = 300,486); or, 2) g Factor constructed using genomic structural equation modelling (N = 11,263–331,679). Findings for candidate causal proteins were replicated using a separate protein GWAS in Icelanders (N = 35,559).Results: A higher concentration of genetically predicted circulatory myeloperoxidase (MPO) was nominally associated with better cognitive performance (p < 0.05) using different selection criteria for genetic instruments. Particularly, brain-specific cis-eQTL predicted MPO, which accounts for protein-coding gene expression in brain tissues, was associated with general cognitive function (βWald = 0.22, PWald = 2.4 × 10−4). The posterior probability for colocalization (PP.H4) of MPO pQTL with the g Factor was 0.577. Findings for MPO were replicated using the Icelandic GWAS. Although we did not find evidence for colocalization, we found that higher gene
Kojouri M, Pinto R, Mustafa R, et al., 2023, Metabolome-wide association study on physical activity, Scientific Reports, Vol: 13, Pages: 1-9, ISSN: 2045-2322
The underlying mechanisms linking physical activity to better health are not fully understood. Here we examined the associations between physical activity and small circulatory molecules, the metabolome, to highlight relevant biological pathways. We examined plasma metabolites associated with self-reported physical activity among 2217 participants from the Airwave Health Monitoring Study. Metabolic profiling was conducted using the mass spectrometry-based Metabolon platform (LC/GC–MS), measuring 828 known metabolites. We replicated our findings in an independent subset of the study (n = 2971) using untargeted LC–MS. Mendelian randomisation was carried out to investigate potential causal associations between physical activity, body mass index, and metabolites. Higher vigorous physical activity was associated (P < 0.05/828 = 6.03 × 10–5) with circulatory levels of 28 metabolites adjusted for age, sex and body mass index. The association was inverse for glutamate and diacylglycerol lipids, and direct for 3–4-hydroxyphenyllactate, phenyl lactate (PLA), alpha-hydroxy isovalerate, tiglylcarnitine, alpha-hydroxyisocaproate, 2-hydroxy-3-methylvalerate, isobutyrylcarnitine, imidazole lactate, methionine sulfone, indole lactate, plasmalogen lipids, pristanate and fumarate. In the replication panel, we found 23 untargeted LC–MS features annotated to the identified metabolites, for which we found nominal associations with the same direction of effect for three features annotated to 1-(1-enyl-palmitoyl)-2-oleoyl-GPC (P-16:0/18:1), 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2), 1-stearoyl-2-dihomo-linolenoyl-GPC (18:0/20:3n3 or 6). Using Mendelian randomisation, we showed a potential causal relationship between body mass index and three identified metabolites. Circulatory metabolites are associated with physical activity and may play a role in mediating its health effects.
Huang J, Su B, Karhunen V, et al., 2023, Inflammatory diseases, inflammatory biomarkers, and Alzheimer disease: an observational analysis and mendelian randomization, Neurology, Vol: 100, Pages: e568-e581, ISSN: 0028-3878
OBJECTIVES: Whether chronic autoimmune inflammatory diseases causally affect the risk of AD is controversial. We characterised the relationship between inflammatory diseases and the risk of AD and explore the role of circulating inflammatory biomarkers in the relationships between inflammatory diseases and AD. METHODS: We performed observational analyses for chronic autoimmune inflammatory diseases and risk of AD using data from 2,047,513 participants identified in the UK Clinical Practice Research Datalink (CPRD). Using data of a total of more than 1,100,000 individuals from 15 large scale genome-wide association study (GWAS) datasets, we performed two-sample Mendelian randomisation (MR) to investigate the relationships between chronic autoimmune inflammatory diseases, circulating inflammatory biomarker levels, and risk of AD. RESULTS: Cox regression models using CPRD data showed that overall incidence of AD was higher among patients with inflammatory bowel disease (IBD) (hazard ratio (HR)=1.17; 95%CI 1.15 to 1.19; P-value=2.1×10-4), other inflammatory polyarthropathies & systematic connective tissue disorders (OID) (HR=1.13; 95%CI 1.12 to 1.14; P-value=8.6×10-5), psoriasis (HR=1.13; 95%CI 1.10 to 1.16; P-value=2.6×10-4), rheumatoid arthritis (RA) (HR=1.08; 95%CI 1.06 to 1.11; P-value=4.0×10-4), and multiple sclerosis (MS) (HR=1.06; 95%CI 1.04 to 1.07; P-value=2.8×10-4) compared to the age (± 5 years) and sex-matched comparison groups free from all inflammatory diseases under investigation. Bidirectional MR analysis identified relationships between chronic autoimmune inflammatory diseases and circulating inflammatory biomarkers. Particularly, circulating monokine induced by gamma interferon (MIG) level was suggestively associated with a higher risk of AD (odds ratio from inverse variance weighted (ORIVW)=1.23; 95%CI 1.06 to 1.42; PIVW=0.007), and lower risk of Crohn's disease (ORIVW=0.73; 95%CI -0.62, 0.86; PIVW=1.3×10
Francis C, Futschik M, Huang J, et al., 2022, Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities, Nature Communications, Vol: 13, ISSN: 2041-1723
Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease.
Huang J, Law E, Karaman I, et al., 2022, Investigation of metabolomic biomarkers for childhood executive function and the role of genetic and dietary factors: The GUSTO cohort, EBIOMEDICINE, Vol: 81, ISSN: 2352-3964
Tsilidis K, 2022, Circulating inflammatory cytokines and risk of five cancers: a mendelian randomization analysis, BMC Medicine, Vol: 20, ISSN: 1741-7015
Background: Epidemiological and experimental evidence has linked chronic inflammation to cancer etiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered genetically-predicted concentration of circulating cytokines are associated with cancer development, we performed a two-sample Mendelian randomization (MR) analysis.Methods: Up to 31,112 individuals of European descent were included in genome-wide association study (GWAS) meta-analyses of 47 circulating cytokines. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene (cis), were used as instrumental variables. Inverse-variance weighted MR was used as the primary analysis, and the MR assumptions were evaluated in sensitivity and colocalization analyses and a false discovery rate (FDR) correction for multiple comparisons was applied. Corresponding germline GWAS summary data for five cancer outcomes (breast, endometrial, lung, ovarian and prostate) and their subtypes were selected from the largest cancer-specific GWASs available (cases ranging from 12 906 for endometrial to 133 384 for breast cancer). Results: There was evidence of inverse associations of macrophage migration inhibitory factor with breast cancer (OR per SD = 0.88, 95%CI: 0.83 to 0.94), interleukin-1 receptor antagonist with endometrial cancer (0.86, 0.80 to 0.93), interleukin-18 with lung cancer (0.87, 0.81 to 0.93), and beta-chemokine-RANTES with ovarian cancer (0.70, 0.57 to 0.85); and positive associations of monokine induced by gamma interferon with endometrial cancer (3.73, 1.86 to 7.47) and cutaneous T-cell attracting chemokine with lung cancer (1.51, 1.22 to 1.87). These associations were similar in sensitivity analyses and supported in colocalization analyses. Conclusions: Our study adds to current knowledge on the role of specific inflammatory biomarker pathways in cancer etiology. Further va
Karabegović I, Dehghan A, Elliott P, et al., 2021, Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption, Nature Communications, Vol: 12, ISSN: 2041-1723
Coffee and tea are extensively consumed beverages worldwide which have received considerable attention regarding health. Intake of these beverages is consistently linked to, among others, reduced risk of diabetes and liver diseases; however, the mechanisms of action remain elusive. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. Here we report the results from epigenome-wide association studies (EWAS) on coffee and tea consumption in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis of coffee consumption reveals 11 CpGs surpassing the epigenome-wide significance threshold (P-value <1.1×10−7), which annotated to the AHRR, F2RL3, FLJ43663, HDAC4, GFI1 and PHGDH genes. Among them, cg14476101 is significantly associated with expression of the PHGDH and risk of fatty liver disease. Knockdown of PHGDH expression in liver cells shows a correlation with expression levels of genes associated with circulating lipids, suggesting a role of PHGDH in hepatic-lipid metabolism. EWAS meta-analysis on tea consumption reveals no significant association, only two CpGs annotated to CACNA1A and PRDM16 genes show suggestive association (P-value <5.0×10−6). These findings indicate that coffee-associated changes in DNA methylation levels may explain the mechanism of action of coffee consumption in conferring risk of diseases.
He Z, Chin Y, Yu S, et al., 2021, The Influence of Average Temperature and Relative Humidity on New Cases of COVID-19: Time-Series Analysis, JMIR PUBLIC HEALTH AND SURVEILLANCE, Vol: 7, Pages: 231-244, ISSN: 2369-2960
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- Citations: 16
Huang J, Zuber V, Matthews P, et al., 2020, Sleep, major depressive disorder and Alzheimer’s disease: a Mendelian randomisation study, Neurology, Vol: 95, ISSN: 0028-3878
ObjectiveTo explore the causal relationships between sleep, major depressive disorder (MDD), and Alzheimer’s disease (AD).MethodsWe conducted bi-directional two-sample Mendelian randomisation analyses. Genetic associations were obtained from the largest genome-wide association studies currently available in UK Biobank (N=446,118), the Psychiatric Genomics Consortium (N=18,759), and the International Genomics of Alzheimer’s Project (N=63,926). We used the inverse variance weighted Mendelian randomisation method to estimate causal effects, and weighted median and MR-Egger for sensitivity analyses to test for pleiotropic effects. ResultsWe found that higher risk of AD was significantly associated with being a “morning person” (odds ratio (OR)=1.01, P=0.001), shorter sleep duration (self-reported: β=-0.006, P=1.9×10-4; accelerometer-based: β=-0.015, P=6.9×10-5), less likely to report long sleep (β=-0.003, P=7.3×10-7), earlier timing of the least active 5 hours (β=-0.024, P=1.7×10-13), and a smaller number of sleep episodes (β=-0.025, P=5.7×10-14) after adjusting for multiple comparisons. We also found that higher risk of AD was associated with lower risk of insomnia (OR=0.99, P=7×10-13). However, we did not find evidence either that these abnormal sleep patterns were causally related to AD or for a significant causal relationship between MDD and risk of AD. ConclusionWe found that AD may causally influence sleep patterns. However, we did not find evidence supporting a causal role of disturbed sleep patterns for AD or evidence for a causal relationship between MDD and AD.
Bai W, Suzuki H, Huang J, et al., 2020, A population-based phenome-wide association study of cardiac and aortic structure and function, Nature Medicine, Vol: 26, Pages: 1654-1662, ISSN: 1078-8956
Differences in cardiac and aortic structure and function are associated with cardiovascular diseases and a wide range of other types of disease. Here we analyzed cardiovascular magnetic resonance images from a population-based study, the UK Biobank, using an automated machine-learning-based analysis pipeline. We report a comprehensive range of structural and functional phenotypes for the heart and aorta across 26,893 participants, and explore how these phenotypes vary according to sex, age and major cardiovascular risk factors. We extended this analysis with a phenome-wide association study, in which we tested for correlations of a wide range of non-imaging phenotypes of the participants with imaging phenotypes. We further explored the associations of imaging phenotypes with early-life factors, mental health and cognitive function using both observational analysis and Mendelian randomization. Our study illustrates how population-based cardiac and aortic imaging phenotypes can be used to better define cardiovascular disease risks as well as heart–brain health interactions, highlighting new opportunities for studying disease mechanisms and developing image-based biomarkers.
He Z, Zhang CJP, Huang J, et al., 2020, A new era of epidemiology: Digital epidemiology for investigating the novel coronaviral disease (COVID-19) outbreak in China, Journal of Medical Internet Research, Vol: 22, ISSN: 1438-8871
UNSTRUCTURED: A novel pneumonia like disease outbreak named the 2019 Coronavirus disease (COVID-19) caused by a novel coronavirus, a.k.a. the severe acute respiratory syndrome (SARS)-CoV-2, has swept China and then globally. Public health measures that showed effectiveness in previous infection outbreaks (e.g., facemask wear, quarantine) were implemented in this outbreak. Available multidimensional social network data that take advantage of recent rapid development of information and communication technologies allow for an exploration of the disease spread and control via a modernised epidemiological approach. By using spatiotemporal data and real-time information, we can provide more accurate estimates of spread patterns related to human activities and more efficient responses to the outbreak control. Two real cases during the COVID-19 outbreak demonstrated the applications of emerging technologies and digital data in monitoring human movements related to the disease spread. Although the ethics of digital epidemiology is still under debate, the cases reported in this article may provide insight into identifying more effective public health measures, and the future application of such digital-directed epidemiological approach in controlling the infectious disease outbreak and offer an alternative and modern outlook on addressing the long-standing challenges in population health.
Wu H-L, Huang J, Zhang CJP, et al., 2020, Facemask shortage and the novel coronavirus disease (COVID-19) outbreak: Reflections on public health measures., EClinicalMedicine, Vol: 21, Pages: 100329-100329, ISSN: 2589-5370
Background: A novel coronavirus disease (COVID-19) outbreak due to the severe respiratory syndrome coronavirus (SARS-CoV-2) infection occurred in China in late December 2019. Facemask wearing with proper hand hygiene is considered an effective measure to prevent SARS-CoV-2 transmission, but facemask wearing has become a social concern due to the global facemask shortage. China is the major facemask producer in the world, contributing to 50% of global production. However, a universal facemask wearing policy would put an enormous burden on the facemask supply. Methods: We performed a policy review concerning facemasks using government websites and mathematical modelling shortage analyses based on data obtained from the National Health Commission (NHC), the Ministry of Industry and Information Technology (MIIT), the Centre for Disease Control and Prevention (CDC), and General Administration of Customs (GAC) of the People's Republic of China. Three scenarios with respect to wearing facemasks were considered: (1) a universal facemask wearing policy implementation in all regions of mainland China; (2) a universal facemask wearing policy implementation only in the epicentre (Hubei province, China); and (3) no implementation of a universal facemask wearing policy. Findings: Regardless of different universal facemask wearing policy scenarios, facemask shortage would occur but eventually end during our prediction period (from 20 Jan 2020 to 30 Jun 2020). The duration of the facemask shortage described in the scenarios of a country-wide universal facemask wearing policy, a universal facemask wearing policy in the epicentre, and no universal facemask wearing policy were 132, seven, and four days, respectively. During the prediction period, the largest daily facemask shortages were predicted to be 589·5, 49·3, and 37·5 million in each of the three scenarios, respectively. In any scenario, an N95 mask shortage was predicted to occur on 24 January 2020 with a
Huang JV, Leung GM, Schooling CM, 2019, The association of air pollution with body mass index: evidence from Hong Kong’s “Children of 1997” birth cohort, International Journal of Obesity, Vol: 43, Pages: 62-72, ISSN: 0307-0565
Huang JV, Cardenas A, Colicino E, et al., 2018, DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence, Epigenetics, Vol: 13, Pages: 1072-1087, ISSN: 1559-2294
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