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  1. Assessment of the factors contributing to the variations in microcystins biodegradability of the biofilms on a practical biological treatment facility
    Li J, Shimizu K, Akasako H, Lu Z, Akiyama S, Goto M, et al.
    Bioresour Technol, 2015 Jan;175:463-72.
    PMID: 25459856 DOI: 10.1016/j.biortech.2014.10.047
    This study revealed the biotic and abiotic parameters driving the variations in microcystins (MCs) biodegradability of a practical biological treatment facility (BTF). Results showed that similar trends of seasonal variation were seen for microcystin-LR (MCLR) biodegradability of biofilms on the BTF and indigenous MCLR-degrader population, where both peaks co-occurred in October, following the peaks of natural MCLR concentration and water temperature observed in August. The lag period might be required for accumulation of MCLR-degraders and MCLR-degrading enzyme activity. The MCLR-degrader population was correlated to temperature, MCLR and chlorophyll-a concentration in water where the biofilms submerged, indicating that these abiotic and biotic parameters exerted direct and/or indirect influences on seasonal variation in MCLR-biodegradability. In comparison, no effect of other co-existing MCs on biodegradation of one MC was observed. However, proliferation of MC-degraders along biodegradation processes positively responded to total amount of MCs, suggesting that multiple MCs contributed additively to MC-degrader proliferation.
  2. Overproduction of lipoxygenase from Pseudomonas aeruginosa in Escherichia coli by auto-induction expression and its application in triphenylmethane dyes degradation
    Lu J, Zhang C, Leong HY, Show PL, Lu F, Lu Z
    J Biosci Bioeng, 2020 Mar;129(3):327-332.
    PMID: 31585857 DOI: 10.1016/j.jbiosc.2019.09.006
    In this study, the bacterial lipoxygenase (LOX) gene from Pseudomonas aeruginosa ATCC27853 (pse-LOX) was cloned, sequenced and heterologous expressed in Escherichia coli by auto-induction expression strategy. Production of the recombinant pse-LOX (pse-rLOX) gene up to 23,850 U/mL (264 mg pure protein/L bacterial culture fluid) was observed in the end of this process. To the best of our knowledge, this is the first attempt to manipulate LOX heterologous expression process using auto-induction expression approach, and it is the highest production of recombinant LOX compared with other reports. Subsequently, the resulted pse-rLOX was proved to efficiently degrade triphenylmethane dyes such as malachite green, brilliant green and aniline blue. Generally, an overproduction of the LOX from P. aeruginosa was observed in E. coli, and this recombinant gene is a potential candidate as biocatalyst for triphenylmethane dyes decolorization.
  3. Surface active complexes formed between keratin polypeptides and ionic surfactants
    Pan F, Lu Z, Tucker I, Hosking S, Petkov J, Lu JR
    J Colloid Interface Sci, 2016 Dec 15;484:125-134.
    PMID: 27599381 DOI: 10.1016/j.jcis.2016.08.082
    Keratins are a group of important proteins in skin and hair and as biomaterials they can provide desirable properties such as strength, biocompatibility, and moisture regaining and retaining. The aim of this work is to develop water-soluble keratin polypeptides from sheep wool and then explore how their surface adsorption behaves with and without surfactants. Successful preparation of keratin samples was demonstrated by identification of the key components from gel electrophoresis and the reproducible production of gram scale samples with and without SDS (sodium dodecylsulphate) during wool fibre dissolution. SDS micelles could reduce the formation of disulphide bonds between keratins during extraction, reducing inter-molecular crosslinking and improving keratin polypeptide solubility. However, Zeta potential measurements of the two polypeptide batches demonstrated almost identical pH dependent surface charge distributions with isoelectric points around pH 3.5, showing complete removal of SDS during purification by dialysis. In spite of different solubility from the two batches of keratin samples prepared, very similar adsorption and aggregation behavior was revealed from surface tension measurements and dynamic light scattering. Mixing of keratin polypeptides with SDS and C12TAB (dodecyltrimethylammonium bromide) led to the formation of keratin-surfactant complexes that were substantially more effective at reducing surface tension than the polypeptides alone, showing great promise in the delivery of keratin polypeptides via the surface active complexes. Neutron reflection measurements revealed the coexistence of surfactant and keratin polypeptides at the interface, thus providing the structural support to the observed surface tension changes associated with the formation of the surface active complexes.
  4. Characterization of a novel type I l-asparaginase from Acinetobacter soli and its ability to inhibit acrylamide formation in potato chips
    Jiao L, Chi H, Lu Z, Zhang C, Chia SR, Show PL, et al.
    J Biosci Bioeng, 2020 Jun;129(6):672-678.
    PMID: 32088137 DOI: 10.1016/j.jbiosc.2020.01.007
    l-Asparaginases have the potential to inhibit the formation of acrylamide, a harmful toxin formed during high temperature processing of food. A novel bacterium which produces l-asparaginase was screened. Type I l-asparaginase gene from Acinetobacter soli was cloned and expressed in Escherichia coli. The recombinant l-asparaginase had an activity of 42.0 IU mL-1 and showed no activity toward l-glutamine and d-asparagine. The recombinant l-asparaginase exhibited maximum catalytic activity at pH 8.0 and 40°C. The enzyme was stable in the pH ranging from 6.0 to 9.0. The activity of the recombinant enzyme was substantially enhanced by Ba2+, dithiothreitol, and β-mercaptoethanol. The Km and Vmax values of the l-asparaginase for the l-asparagine were 3.22 mmol L-1 and 1.55 IU μg-1, respectively. Moreover, the recombinant l-asparaginase had the ability to mitigate acrylamide formation in potato chips. Compared with the untreated group, the content of acrylamide in samples treated with the enzyme was effectively decreased by 55.9%. These results indicate that the novel type I l-asparaginase has the potential for application in the food processing industry.
  5. Fulltext CNPase, a 2',3'-Cyclic-nucleotide 3'-phosphodiesterase, as a Therapeutic Target to Attenuate Cardiac Hypertrophy by Enhancing Mitochondrial Energy Production
    Tan KS, Wang D, Lu Z, Zhang Y, Li S, Lin Y, et al.
    Int J Mol Sci, 2021 Oct 06;22(19).
    PMID: 34639145 DOI: 10.3390/ijms221910806
    Heart failure is the end-stage of all cardiovascular diseases with a ~25% 5-year survival rate, and insufficient mitochondrial energy production to meet myocardial demand is the hallmark of heart failure. Mitochondrial components involved in the regulation of ATP production remain to be fully elucidated. Recently, roles of 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in the pathophysiological processes of heart diseases have emerged, implicated by evidence that mitochondrial CNPase proteins are associated with mitochondrial integrity under metabolic stress. In this study, a zebrafish heart failure model was established, by employing antisense morpholino oligonucleotides and the CRISPR-Cas9 gene-editing system, which recapitulates heart failure phenotypes including heart dysfunction, pericardial edema, ventricular enlargement, bradycardia, and premature death. The translational implications of CNPase in the pathophysiological process of heart failure were tested in a pressure overload-induced heart hypertrophy model, which was carried out in rats through transverse abdominal aorta constriction (TAAC). AAV9-mediated myocardial delivery of CNPase mitigated the hypertrophic response through the specific hydrolysis of 2'-3'-cyclic nucleotides, supported by the decrease of cardiac hypertrophy and fibrosis, the integrity of mitochondrial ultrastructure, and indicators of heart contractility in the AAV9-TAAC group. Finally, the biometrics of a mitochondrial respiration assay carried out on a Seahorse cellular energy analyzer demonstrated that CNPase protects mitochondrial respiration and ATP production from AngII-induced metabolic stress. In summary, this study provides mechanistic insights into CNPase-2',3'-cyclic nucleotide metabolism that protects the heart from energy starvation and suggests novel therapeutic approaches to treat heart failure by targeting CNPase activity.
  6. Therapeutic evaluation and metabolic reprograming of isosteviol sodium in a rat model of ischemic cardiomyopathy
    Cao Y, Lu Z, Wang D, Tan KS, Liu W, Wu Q, et al.
    Eur J Pharmacol, 2021 Nov 15;911:174539.
    PMID: 34599913 DOI: 10.1016/j.ejphar.2021.174539
    Ischemia heart disease, one of the lethal cardiovascular diseases, irreversibly impairs cardiac function and is recognized as the primary risk factor for mortality in industrialized countries. The myocardial ischemia treatment still faces a considerable degree of increasing unmet needs. Isosteviol sodium (STVNa) and its derivatives have been proven to effectively alleviate metabolic diseases, hypertension, and heart hypertrophy. Little is known about how STVNa confers the cardioprotective effect during acute myocardial ischemia (AMI). In the present study, a rat model of acute ST-segment-elevation myocardial ischemia by left anterior descending (LAD) ligation was established. Compared to the AMI model group, STVNa administration (4 mg/kg, twice a day) well preserved left ventricle function by ejection fraction (45.10 ± 10.39 vs. 73.64 ± 13.15, p = 0.0013) and fractional shortening (22.94 ± 6.28 vs. 44.00 ± 11.05, p = 0.0017). Further analysis shows that high-dose STVNa (4 mg/kg) significantly improved the hemodynamics in AMI rats, with LVSP (88.25 ± 12.78 vs 99.75 ± 5.10, p = 0.018), max dP/dt (2978.45 ± 832.46 vs 4048.56 ± 827.23, p = 0.096), LVEDP (19.88 ± 2.00 vs 22.26 ± 3.21, p = 0.04) and left ventricular relaxation time constant (Tau) (0.030 ± 0.006 vs 0.021 ± 0.004, p = 0.021). Mechanically, STVNa administration retained the myocardial levels of phosphorylated AMPK, and CPT1b. Moreover, STVNa significantly increased the total energy expenditure, and reduced fatty acid accumulation through mitochondrial oxidative phosphorylation, which was supported by the indirect calorimetry and cellular energy analysis. Taken together, these findings suggest that STVNa is a potential cardioprotection agent for ischemic cardiomyopathy, likely through improving energy homeostasis, left ventricular hemodynamics, and heart function.
  7. Blue carbon sink capacity of mangroves determined by leaves and their associated microbiome
    Lu Z, Qin G, Gan S, Liu H, Macreadie PI, Cheah W, et al.
    Glob Chang Biol, 2024 Jan;30(1):e17007.
    PMID: 37916453 DOI: 10.1111/gcb.17007
    Mangroves play a globally significant role in carbon capture and storage, known as blue carbon ecosystems. Yet, there are fundamental biogeochemical processes of mangrove blue carbon formation that are inadequately understood, such as the mechanisms by which mangrove afforestation regulates the microbial-driven transfer of carbon from leaf to below-ground blue carbon pool. In this study, we addressed this knowledge gap by investigating: (1) the mangrove leaf characteristics using state-of-the-art FT-ICR-MS; (2) the microbial biomass and their transformation patterns of assimilated plant-carbon; and (3) the degradation potentials of plant-derived carbon in soils of an introduced (Sonneratia apetala) and a native mangrove (Kandelia obovata). We found that biogeochemical cycling took entirely different pathways for S. apetala and K. obovata. Blue carbon accumulation and the proportion of plant-carbon for native mangroves were high, with microbes (dominated by K-strategists) allocating the assimilated-carbon to starch and sucrose metabolism. Conversely, microbes with S. apetala adopted an r-strategy and increased protein- and nucleotide-biosynthetic potentials. These divergent biogeochemical pathways were related to leaf characteristics, with S. apetala leaves characterized by lower molecular-weight, C:N ratio, and lignin content than K. obovata. Moreover, anaerobic-degradation potentials for lignin were high in old-aged soils, but the overall degradation potentials of plant carbon were age-independent, explaining that S. apetala age had no significant influences on the contribution of plant-carbon to blue carbon. We propose that for introduced mangroves, newly fallen leaves release nutrient-rich organic matter that favors growth of r-strategists, which rapidly consume carbon to fuel growth, increasing the proportion of microbial-carbon to blue carbon. In contrast, lignin-rich native mangrove leaves shape K-strategist-dominated microbial communities, which grow slowly and store assimilated-carbon in cells, ultimately promoting the contribution of plant-carbon to the remarkable accumulation of blue carbon. Our study provides new insights into the molecular mechanisms of microbial community responses during reforestation in mangrove ecosystems.
  8. Application of Semi-supervised Fuzzy Clustering Based on Knowledge Weighting and Cluster Center Learning to Mammary Molybdenum Target Image Segmentation
    Peng P, Wu D, Huang LJ, Wang J, Zhang L, Wu Y, et al.
    Interdiscip Sci, 2024 Mar;16(1):39-57.
    PMID: 37486420 DOI: 10.1007/s12539-023-00580-0
    Breast cancer is commonly diagnosed with mammography. Using image segmentation algorithms to separate lesion areas in mammography can facilitate diagnosis by doctors and reduce their workload, which has important clinical significance. Because large, accurately labeled medical image datasets are difficult to obtain, traditional clustering algorithms are widely used in medical image segmentation as an unsupervised model. Traditional unsupervised clustering algorithms have limited learning knowledge. Moreover, some semi-supervised fuzzy clustering algorithms cannot fully mine the information of labeled samples, which results in insufficient supervision. When faced with complex mammography images, the above algorithms cannot accurately segment lesion areas. To address this, a semi-supervised fuzzy clustering based on knowledge weighting and cluster center learning (WSFCM_V) is presented. According to prior knowledge, three learning modes are proposed: a knowledge weighting method for cluster centers, Euclidean distance weights for unlabeled samples, and learning from the cluster centers of labeled sample sets. These strategies improve the clustering performance. On real breast molybdenum target images, the WSFCM_V algorithm is compared with currently popular semi-supervised and unsupervised clustering algorithms. WSFCM_V has the best evaluation index values. Experimental results demonstrate that compared with the existing clustering algorithms, WSFCM_V has a higher segmentation accuracy than other clustering algorithms, both for larger lesion regions like tumor areas and for smaller lesion areas like calcification point areas.
  9. Changing Geographic Distribution of Japanese Encephalitis Virus Genotypes, 1935-2017
    Gao X, Liu H, Li X, Fu S, Cao L, Shao N, et al.
    Vector Borne Zoonotic Dis, 2019 Jan;19(1):35-44.
    PMID: 30207876 DOI: 10.1089/vbz.2018.2291
    Japanese encephalitis virus (JEV) is a representative virus of the JEV serogroup in genus Flavivirus, family Flaviviridae. JEV is a mosquito-borne virus that causes Japanese encephalitis (JE), one of the most severe viral encephalitis diseases in the world. JEV is divided into five genotypes (G1-G5), and each genotype has its own distribution pattern. However, the distribution of different JEV genotypes has changed markedly in recent years. JEV G1 has replaced G3 as the dominant genotype in the traditional epidemic areas in Asia, while G3 has spread from Asia to Europe and Africa and caused domestic JE cases in Africa. G2 and G5, which were endemic in Malaysia, exhibited great geographical changes as well. G2 migrated southward and led to prevalence of JE in Australia, while G5 emerged in China and South Korea after decades of silence. Along with these changes, JE occurred in some non-traditional epidemic regions as an emerging infectious disease. The regional changes in JEV pose a great threat to human health, leading to huge disease burdens. Therefore, it is of great importance to strengthen the monitoring of JEV as well as virus genotypes, especially in non-traditional epidemic areas.
  10. Comparison of common human respiratory pathogens among hospitalized children aged ≤ 6 years in Hainan Island, China, during spring and early summer in 2019-2021
    Mai W, Ren Y, Tian X, Al-Mahdi AY, Peng R, An J, et al.
    J Med Virol, 2023 Apr;95(4):e28692.
    PMID: 36946502 DOI: 10.1002/jmv.28692
    The coronavirus disease 2019 (COVID-19) pandemic and related public health intervention measures have been reported to have resulted in the reduction of infections caused by influenza viruses and other common respiratory viruses. However, the influence may be varied in areas that have different ecological, economic, and social conditions. This study investigated the changing epidemiology of 8 common respiratory pathogens, including Influenza A (IFVA), Influenza B (IFVB), Respiratory syncytial virus (HRSV), rhinovirus (RV), Human metapneumovirus Adenovirus, Human bocavirus, and Mycoplasma pneumoniae, among hospitalized children during spring and early summer in 2019-2021 in two hospitals in Hainan Island, China, in the COVID-19 pandemic era. The results revealed a significant reduction in the prevalence of IFVA and IFVB in 2020 and 2021 than in 2019, whereas the prevalence of HRSV increased, and it became the dominant viral pathogen in 2021. RV was one of the leading pathogens in the 3 year period, where no significant difference was observed. Phylogenetic analysis revealed close relationships among the circulating respiratory viruses. Large scale studies are needed to study the changing epidemiology of seasonal respiratory viruses to inform responses to future respiratory virus pandemics.
  11. Fulltext Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic oesophageal cancer: a JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS
    Muro K, Lordick F, Tsushima T, Pentheroudakis G, Baba E, Lu Z, et al.
    Ann Oncol, 2019 Jan 01;30(1):34-43.
    PMID: 30475943 DOI: 10.1093/annonc/mdy498
    The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of oesophageal cancer was published in 2016, and covered the management and treatment of local/locoregional disease, limited disease, locally advanced disease and the management of advanced/metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic oesophageal cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic oesophageal cancer representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.
  12. Fulltext Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic gastric cancer: a JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS
    Muro K, Van Cutsem E, Narita Y, Pentheroudakis G, Baba E, Li J, et al.
    Ann Oncol, 2019 Jan 01;30(1):19-33.
    PMID: 30475956 DOI: 10.1093/annonc/mdy502
    The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of gastric cancer (GC) was published in 2016, and covered the management and treatment of local, locoregional, locally advanced and metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and The Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic GC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic GC representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.
  13. The prevalence and clinical correlates of suicide attempts in patients with bipolar disorder misdiagnosed with major depressive disorder: Results from a national survey in China
    Chen L, Xu YY, Lin JY, Ji ZP, Yang F, Tan S, et al.
    Asian J Psychiatr, 2024 Mar;93:103958.
    PMID: 38364597 DOI: 10.1016/j.ajp.2024.103958
    BACKGROUND AND AIM: Suicide is nearly always associated with underlying mental disorders. Risk factors for suicide attempts (SAs) in patients with bipolar disorder (BD) misdiagnosed with major depressive disorder (MDD) remain unelucidated. This study was to evaluate the prevalence and clinical risk factors of SAs in Chinese patients with BD misdiagnosed with MDD.

    METHODS: A total of 1487 patients with MDD from 13 mental health institutions in China were enrolled. Mini International Neuropsychiatric Interview (MINI) was used to identify patients with BD who are misdiagnosed as MDD. The general sociodemographic and clinical data of the patients were collected and MINI suicide module was used to identify patients with SAs in these misdiagnosed patients.

    RESULTS: In China, 20.6% of patients with BD were incorrectly diagnosed as having MDD. Among these misdiagnosed patients, 26.5% had attempted suicide. These patients tended to be older, had a higher number of hospitalizations, and were more likely to experience frequent and seasonal depressive episodes with atypical features, psychotic symptoms, and suicidal thoughts. Frequent depressive episodes and suicidal thoughts during depression were identified as independent risk factors for SAs. Additionally, significant sociodemographic and clinical differences were found between individuals misdiagnosed with MDD in BD and patients with MDD who have attempted suicide.

    CONCLUSIONS: This study highlights the importance of accurate diagnosis in individuals with BD and provide valuable insights for the targeted identification and intervention of individuals with BD misdiagnosed as having MDD and those with genuine MDD, particularly in relation to suicidal behavior.

  14. Multi-country evidence that crop diversification promotes ecological intensification of agriculture
    Gurr GM, Lu Z, Zheng X, Xu H, Zhu P, Chen G, et al.
    Nat Plants, 2016 02 22;2:16014.
    PMID: 27249349 DOI: 10.1038/nplants.2016.14
    Global food security requires increased crop productivity to meet escalating demand(1-3). Current food production systems are heavily dependent on synthetic inputs that threaten the environment and human well-being(2,4,5). Biodiversity, for instance, is key to the provision of ecosystem services such as pest control(6,7), but is eroded in conventional agricultural systems. Yet the conservation and reinstatement of biodiversity is challenging(5,8,9), and it remains unclear whether the promotion of biodiversity can reduce reliance on inputs without penalizing yields on a regional scale. Here we present results from multi-site field studies replicated in Thailand, China and Vietnam over a period of four years, in which we grew nectar-producing plants around rice fields, and monitored levels of pest infestation, insecticide use and yields. Compiling the data from all sites, we report that this inexpensive intervention significantly reduced populations of two key pests, reduced insecticide applications by 70%, increased grain yields by 5% and delivered an economic advantage of 7.5%. Additional field studies showed that predators and parasitoids of the main rice pests, together with detritivores, were more abundant in the presence of nectar-producing plants. We conclude that a simple diversification approach, in this case the growth of nectar-producing plants, can contribute to the ecological intensification of agricultural systems.
  15. Genomic bacterial load associated with bacterial genotypes and clinical characteristics in patients with scrub typhus in Hainan Island, Southern China
    Wang G, Fu R, Zhang L, Xue L, Al-Mahdi AY, Xie X, et al.
    PLoS Negl Trop Dis, 2023 Apr 21;17(4):e0011243.
    PMID: 37083859 DOI: 10.1371/journal.pntd.0011243
    Scrub typhus, caused by mite-borne Orientia tsutsugamushi (O. tsutsugamushi), is a major febrile disease in the Asia-Pacific region. The DNA load of O. tsutsugamushi in the blood was previously found to be significantly higher in patients with fatal disease than those with non-fatal disease and correlated with the duration of illness, presence of eschar, and hepatic enzyme levels. In this prospective observation study, we analyzed the association of bacterial DNA load with clinical features, disease severity, and genotype using real-time PCR targeting the 56 kDa TSA gene of O. tsutsugamushi in the blood samples of 117 surviving patients with scrub typhus who had not received appropriate antibiotic treatment. The median O. tsutsugamushi DNA load was 3.11×103 copies/mL (range, 44 to 3.3×106 copies/mL). The severity of patients was categorized as mild, moderate, and severe based on the number of dysfunctional organs, and no significant difference in O. tsutsugamushi DNA load was found among these groups. Patients infected with the Karp group showed a significantly higher O. tsutsugamushi DNA load than those in the Gilliam (P 
  16. Fulltext Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
    Wang A, Shen J, Rodriguez AA, Saunders EJ, Chen F, Janivara R, et al.
    Nat Genet, 2023 Dec;55(12):2065-2074.
    PMID: 37945903 DOI: 10.1038/s41588-023-01534-4
    The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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