Displaying publications 1 - 20 of 37 in total

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  1. Zhong J, Jermusyk A, Wu L, Hoskins JW, Collins I, Mocci E, et al.
    J Natl Cancer Inst, 2020 Oct 01;112(10):1003-1012.
    PMID: 31917448 DOI: 10.1093/jnci/djz246
    BACKGROUND: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown.

    METHODS: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples).

    RESULTS: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction.

    CONCLUSIONS: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.

  2. Zhao J, Shi J, Chen X, Lei Y, Tian T, Zhu S, et al.
    Mol Omics, 2024 Mar 25;20(3):192-202.
    PMID: 38224158 DOI: 10.1039/d3mo00232b
    Areca nut (Areca catechu L.) is commonly consumed as a chewing food in the Asian region. However, the investigations into the components of areca nut are limited. In this study, we have developed an approach that combines mass spectrometry with feature-based molecular network to explore the chemical characteristics of the areca nut. In comparison to the conventional method, this technique demonstrates a superior capability in annotating unknown compounds present in areca nut. We annotated a total of 52 compounds, including one potential previously unreported alkaloid, one carbohydrate, and one phenol and confirmed the presence of 7 of them by comparing with commercial standards. The validated method was used to evaluate chemical features of areca nut at different growth stages, annotating 25 compounds as potential biomarkers for distinguishing areca nut growth stages. Therefore, this approach offers a rapid and accurate method for the component analysis of areca nut.
  3. Zhang Y, Shi J, Tan C, Liu Y, Xu YJ
    Food Res Int, 2023 Nov;173(Pt 1):113301.
    PMID: 37803609 DOI: 10.1016/j.foodres.2023.113301
    Oil is one of three nutritious elements. The application of omics techniques in the field of oil science and technology is attracted increasing attention. Oilomics, which emerged as an important branch of foodomics, has been widely used in various aspects of oil science and technology. However, there are currently no articles systematically reviewing the application of oilomics. This paper aims to provide a critical overview of the advantages and value of oilomics technology compared to traditional techniques in various aspects of oil science and technology, including oil nutrition, oil processing, oil quality, safety, and traceability. Moreover, this article intends to review major issues in oilomics and give a comprehensive, critical overview of the current state of the art, future challenges and trends in oilomics, with a view to promoting the optimal application and development of oilomics technology in oil science and technology.
  4. Zhang M, Zhang F, Guo L, Dong P, Cheng C, Kumar P, et al.
    J Environ Manage, 2023 Dec 15;348:119465.
    PMID: 37924697 DOI: 10.1016/j.jenvman.2023.119465
    Grassland degradation poses a serious threat to biodiversity, ecosystem services, and human well-being. In this study, we investigated grassland degradation in Zhaosu County, China, between 2001 and 2020, and analyzed the impacts of climate change and human activities using the Miami model. The actual net primary productivity (ANPP) obtained with CASA (Carnegie-Ames-Stanford Approach) modeling, showed a decreasing trend, reflecting the significant degradation that the grasslands in Zhaosu County have experienced in the past 20 years. Grassland degradation was found to be highest in 2018, while the degraded area continuously decreased in the last 3 years (2018-2020). Climatic factors for found to be the dominant factor affecting grassland degradation, particularly the decrease in precipitation. On the other hand, human activities were found to be the main factor affecting improvement of grasslands, especially in recent years. This finding profoundly elucidates the underlying causes of grassland degradation and improvement and helps implement ecological conservation and restoration measures. From a practical perspective, the research results provide an important reference for the formulation of policies and management strategies for sustainable land use.
  5. Zhang H, Rios RS, Boursier J, Anty R, Chan WK, George J, et al.
    Chin Med J (Engl), 2023 Feb 05;136(3):341-350.
    PMID: 36848175 DOI: 10.1097/CM9.0000000000002603
    BACKGROUND: Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH.

    METHODS: Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL).

    RESULTS: A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P  

  6. Yuan F, Hung RJ, Walsh N, Zhang H, Platz EA, Wheeler W, et al.
    Cancer Res, 2020 Sep 15;80(18):4004-4013.
    PMID: 32641412 DOI: 10.1158/0008-5472.CAN-20-0447
    Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10-6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. SIGNIFICANCE: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.
  7. Xu H, Zhang F, Li W, Shi J, Johnson BA, Tan ML
    Environ Monit Assess, 2023 Dec 27;196(1):94.
    PMID: 38150164 DOI: 10.1007/s10661-023-12249-8
    This study analyzed the spatial-temporal change pattern and underlying factors in production-living-ecological space (PLES) of Nanchong City, China, over the past 20 years using historical land use data (2000, 2010, 2020). A land use transfer matrix was calculated from the historical land use maps, and spatial analysis was conducted to analyze changes in the land use dynamics degree, standard deviation ellipse, and center of gravity. The results showed that there was a rapid spatial evolution of the PLES in Nanchong from 2000 to 2010, followed by a stabilization in the second decade. The transfer of ecological-production space occurred mainly in the Jialing and Yilong River basins, while the reduction of production space and the increase of living space were most prominent in the intersection of three districts (Shunqing, Jialing, and Gaoping districts). The return of production-ecological space was observed in the south and northeast of Yingshan, and there was little notable transfer of other types. The distribution of production space in Nanchong evolved in a north-south to east-west trend, with the center of gravity moving from Yilong to Peng'an County. The living space and production space expanded in a north-south direction, and the center of gravity position was in Nanbu, indicating a more balanced growth or decrease in the last 20 years. The changes in the spatial-temporal pattern of PLES in Nanchong were attributed to the intertwined factors of national policies, economic development, population growth, and the natural environment. This study introduced a novel approach towards rational planning of land resources in Nanchong, which may facilitate more sustainable urban planning and development.
  8. Wei S, Sun B, Liu C, Sokolova I, Waiho K, Fang JKH, et al.
    Sci Total Environ, 2023 Oct 01;893:164836.
    PMID: 37321498 DOI: 10.1016/j.scitotenv.2023.164836
    Nano-TiO2 can act as a vector to organic compounds, such as pentachlorophenol (PCP) posing a potential threat to the marine ecosystems. Studies showed that nano pollutant toxicity can be modulated by abiotic factors, but little is known about the potential influence of biotic stressors (such as predators) on the physiological responses to pollutants in marine organisms. We explored the effects of n-TiO2 and PCP on the mussel Mytilus coruscus in the presence of its natural predator, the swimming crab Portunus trituberculatus. Exposure to n-TiO2, PCP, and predation risk showed interactive effects on antioxidant and immune parameters of the mussels. Elevated activities of catalase (CAT), glutathione peroxidase (GPX), acid phosphatase (ACP) and alkaline phosphatase (AKP), suppressed activity of superoxide dismutase (SOD), lower levels of glutathione (GSH) and increased malondialdehyde (MDA) levels indicated dysregulation of the antioxidant system and immune stress induced by single PCP or n-TiO2 exposure. Integrated biomarker (IBR) response values showed the effect of PCP was concentration dependent. Of the two used n-TiO2 sizes (25 and 100 nm), larger particles induced higher antioxidant and immune disturbances indicating higher toxicity possibly due to higher bioavailability. Compared to single PCP exposure, the combination of n-TiO2 and PCP enhanced the imbalance of SOD/CAT and GSH/GPX and led to elevated oxidative lesions and activation of immune-related enzymes. Overall, the combined impacts of pollutants and biotic stress exhibited a greater magnitude of adverse effects on antioxidant defense and immune parameters in mussels. The toxicological effects of PCP were exacerbated in the presence of n-TiO2, and the deleterious impact of these stressors was further amplified under predator-induced risk after prolonged (28 days) exposure. However, the underlying physiological regulatory mechanisms governing the interplay of these stressors and predatory cues on mussels remain elusive, warranting further investigation.
  9. Wang Y, Shi J, Xu YJ, Tan CP, Liu Y
    Food Chem, 2024 Apr 16;438:137400.
    PMID: 38039864 DOI: 10.1016/j.foodchem.2023.137400
    The digestion behavior of lipids plays a crucial role in their nutritional bioaccessibility, which subsequently impacts human health. This study aims to investigate potential variations in lipid digestion profiles among individuals of different ages, considering the distinct physiological functions of the gastrointestinal tract in infants, aging populations, and healthy young adults. The digestion fates of high oleic peanut oil (HOPO), sunflower oil (SO), and linseed oil (LINO) were investigated using in vitro digestion models representing infants, adults, and elders. Comparatively, lipid digestion proved to be more comprehensive in adults, leading to free fatty acid (FFA) levels of 64.53%, 62.32%, and 57.90% for HOPO, SO, and LINO, respectively. Besides, infants demonstrated propensity to selectively release FFAs with shorter chain lengths and higher saturation levels during the digestion. In addition, in the gastric phase, particle sizes among the elderly were consistently larger than those observed in infants and adults, despite adults generating approximately 15% FFAs within the stomach. In summary, this study enhances our fundamental comprehension of how lipids with varying degrees of unsaturation undergo digestion in diverse age groups.
  10. Sun DQ, Targher G, Byrne CD, Wheeler DC, Wong VW, Fan JG, et al.
    Hepatobiliary Surg Nutr, 2023 Jun 01;12(3):386-403.
    PMID: 37351121 DOI: 10.21037/hbsn-22-421
    BACKGROUND: With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no appropriate guidance on CKD in individuals with MAFLD. Furthermore, there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.

    METHODS AND RESULTS: Using a Delphi-based approach, a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.

    CONCLUSIONS: This Delphi-based consensus statement provided guidance on the epidemiology, mechanisms, management and treatment of MAFLD and CKD, as well as the relationship between the severity of MAFLD and risk of CKD, which establish a framework for the early prevention and management of these two common and interconnected diseases.

  11. Shu X, Long J, Cai Q, Kweon SS, Choi JY, Kubo M, et al.
    Nat Commun, 2020 Mar 05;11(1):1217.
    PMID: 32139696 DOI: 10.1038/s41467-020-15046-w
    Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P 
  12. Shi J, Sun J, Hu N, Hu Y
    Infect Genet Evol, 2020 11;85:104442.
    PMID: 32622923 DOI: 10.1016/j.meegid.2020.104442
    Little is known about the genetic features of Nipah virus (NiV) associated with virulence and transmission. Herein, phylogenetic and genetic analyses for all available NiV strains revealed sequence variations between the two genetic lineages of NiV with pathogenic differences, as well as among different strains within Bangladesh lineage. A total of 143 conserved amino acid differences, distributed among viral nucleocapsid (N), phosphoprotein (P), matrix protein (M), fusion protein (F) and glycoprotein (G), were revealed. Structural modeling revealed one key substitution (S3554N) in the viral G protein that might mediate a 12-amino-acid structural change from a loop into a β sheet. Multiple key amino acids substitutions in viral G protein were observed, which may alter viral fitness and transmissibility from bats to humans.
  13. Shi J, Khoo Z
    Front Psychol, 2023;14:1092884.
    PMID: 37057164 DOI: 10.3389/fpsyg.2023.1092884
    BACKGROUND: A key research question with theoretical and practical implications is to investigate the various conditions by which social network sites (SNS) may either enhance or interfere with mental well-being, given the omnipresence of SNS and their dual effects on well-being.

    METHOD/PROCESS: We study SNS' effects on well-being by accounting for users' personal (i.e., self-disclosure) and situational (i.e., social networks) attributes, using a mixed design of content analysis and social network analysis.

    RESULT/CONCLUSION: We compare users' within-person changes in self-disclosure and social networks in two phases (over half a year), drawing on Weibo Depression SuperTalk, an online community for depression, and find: ① Several network attributes strengthen social support, including network connectivity, global efficiency, degree centralization, hubs of communities, and reciprocal interactions. ② Users' self-disclosure attributes reflect positive changes in mental well-being and increased attachment to the community. ③ Correlations exist between users' topological and self-disclosure attributes. ④ A Poisson regression model extracts self-disclosure attributes that may affect users' received social support, including the writing length, number of active days, informal words, adverbs, negative emotion words, biological process words, and first-person singular forms.

    INNOVATION: We combine social network analysis with content analysis, highlighting the need to understand SNS' effects on well-being by accounting for users' self-disclosure (content) and communication partners (social networks).

    IMPLICATION/CONTRIBUTION: Authentic user data helps to avoid recall bias commonly found in self-reported data. A longitudinal within-person analysis of SNS' effects on well-being is helpful for policymakers in public health intervention, community managers for group organizations, and users in online community engagement.

  14. Shi J, Khoo Z
    Front Psychol, 2023;14:1227123.
    PMID: 37829080 DOI: 10.3389/fpsyg.2023.1227123
    PURPOSE/SIGNIFICANCE: Humans understand, think, and express themselves through metaphors. The current paper emphasizes the importance of identifying the metaphorical language used in online health communities (OHC) to understand how users frame and make sense of their experiences, which can boost the effectiveness of counseling and interventions for this population.

    METHODS/PROCESS: We used a web crawler to obtain a corpus of an online depression community. We introduced a three-stage procedure for metaphor identification in a Chinese Corpus: (1) combine MIPVU to identify metaphorical expressions (ME) bottom-up and formulate preliminary working hypotheses; (2) collect more ME top-down in the corpus by performing semantic domain analysis on identified ME; and (3) analyze ME and categorize conceptual metaphors using a reference list. In this way, we have gained a greater understanding of how depression sufferers conceptualize their experience metaphorically in an under-represented language in the literature (Chinese) of a new genre (online health community).

    RESULTS/CONCLUSION: Main conceptual metaphors for depression are classified into PERSONAL LIFE, INTERPERSONAL RELATIONSHIP, TIME, and CYBERCULTURE metaphors. Identifying depression metaphors in the Chinese corpus pinpoints the sociocultural environment people with depression are experiencing: lack of offline support, social stigmatization, and substitutability of offline support with online support. We confirm a number of depression metaphors found in other languages, providing a theoretical basis for researching, identifying, and treating depression in multilingual settings. Our study also identifies new metaphors with source-target connections based on embodied, sociocultural, and idiosyncratic levels. From these three levels, we analyze metaphor research's theoretical and practical implications, finding ways to emphasize its inherent cross-disciplinarity meaningfully.

  15. Shi J, Kim HK, Salmon CT, Tandoc EC, Goh ZH
    Soc Sci Med, 2024 Jan;340:116431.
    PMID: 38000175 DOI: 10.1016/j.socscimed.2023.116431
    RATIONALE: Countries worldwide faced the same public health crisis that required promoting the same health behavior-vaccinations-during the COVID-19 pandemic. Thus, scholars have a unique opportunity to test behavioral change theories across countries with different cultural backgrounds.

    OBJECTIVE: Employing the extended theory of social normative behavior, this study examines the influence of individual and collective norms on COVID-19 vaccination intention across eight Asian countries. We examine how cultural tightness-looseness, defined as the degree of a culture's emphasis on norms and tolerance of deviant behavior, shapes normative social influence on COVID-19 vaccination intention.

    METHODS: We conducted a multicountry online survey (N = 2676) of unvaccinated individuals in China, Indonesia, Japan, Malaysia, Singapore, South Korea, Thailand, and Vietnam in May and June 2021, when COVID-19 vaccination mandates had not yet been implemented in those countries. We conducted hierarchical regression analyses with interaction terms for the total sample and then re-categorizied the eight countries as either "tight" (n = 1102) or "loose" (n = 1574) to examine three-way interactions between individual norms, collective norms, and cultural tightness-looseness.

    RESULTS: Perceived injunctive norms exerted the strongest impact of all normative factors on vaccination intention. Collective injunctive norms' influence depended on both perceived injunctive and descriptive norms, which was larger when norms were lower (vs. higher). The interactive pattern between perceived and collective norms was more pronounced in countries with greater cultural tightness.

    CONCLUSION: Our findings reveal nuanced patterns of how individual and collective social norms influence health behavioral decisions, depending on the degree of cultural tightness-looseness.

  16. Shi J, Zhao J, Zhang Y, Wang Y, Tan CP, Xu YJ, et al.
    Anal Chem, 2023 Dec 26;95(51):18793-18802.
    PMID: 38095040 DOI: 10.1021/acs.analchem.3c03785
    Metabolomics and proteomics offer significant advantages in understanding biological mechanisms at two hierarchical levels. However, conventional single omics analysis faces challenges due to the high demand for specimens and the complexity of intrinsic associations. To obtain comprehensive and accurate system biological information, we developed a multiomics analytical method called Windows Scanning Multiomics (WSM). In this method, we performed simultaneous extraction of metabolites and proteins from the same sample, resulting in a 10% increase in the coverage of the identified biomolecules. Both metabolomics and proteomics analyses were conducted by using ultrahigh-performance liquid chromatography mass spectrometry (UPLC-MS), eliminating the need for instrument conversions. Additionally, we designed an R-based program (WSM.R) to integrate mathematical and biological correlations between metabolites and proteins into a correlation network. The network created from simultaneously extracted biomolecules was more focused and comprehensive compared to those from separate extractions. Notably, we excluded six pairs of false-positive relationships between metabolites and proteins in the network established using simultaneously extracted biomolecules. In conclusion, this study introduces a novel approach for multiomics analysis and data processing that greatly aids in bioinformation mining from multiomics results. This method is poised to play an indispensable role in systems biology research.
  17. Shi J, Zhang Y, Zheng W, Michailidou K, Ghoussaini M, Bolla MK, et al.
    Int J Cancer, 2016 Sep 15;139(6):1303-1317.
    PMID: 27087578 DOI: 10.1002/ijc.30150
    Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional p = 5.8 × 10(-6) ), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional p = 1.1 × 10(-6) ) and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional p = 1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2)  = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.
  18. Shen Q, Zeng X, Kong L, Sun X, Shi J, Wu Z, et al.
    Foods, 2023 Apr 01;12(7).
    PMID: 37048306 DOI: 10.3390/foods12071485
    Nitrite is a common color and flavor enhancer in fermented meat products, but its secondary amines may transfer to the carcinogen N-nitrosamines. This review focuses on the sources, degradation, limitations, and alteration techniques of nitrite. The transition among NO3- and NO2-, NH4+, and N2 constitutes the balance of nitrogen. Exogenous addition is the most common source of nitrite in fermented meat products, but it can also be produced by contamination and endogenous microbial synthesis. While nitrite is degraded by acids, enzymes, and other metabolites produced by lactic acid bacteria (LAB), four nitrite reductase enzymes play a leading role. At a deeper level, nitrite metabolism is primarily regulated by the genes found in these bacteria. By incorporating antioxidants, chromogenic agents, bacteriostats, LAB, or non-thermal plasma sterilization, the amount of nitrite supplied can be decreased, or even eliminated. Finally, the aim of producing low-nitrite fermented meat products is expected to be achieved.
  19. Peyrot WJ, Lee SH, Milaneschi Y, Abdellaoui A, Byrne EM, Esko T, et al.
    Mol Psychiatry, 2015 Jun;20(6):735-43.
    PMID: 25917368 DOI: 10.1038/mp.2015.50
    An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14,949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15,138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884,105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ~120,000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.
  20. Mullins N, Kang J, Campos AI, Coleman JRI, Edwards AC, Galfalvy H, et al.
    Biol Psychiatry, 2022 Feb 01;91(3):313-327.
    PMID: 34861974 DOI: 10.1016/j.biopsych.2021.05.029
    BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.

    METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.

    RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.

    CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

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