Role Of Environmental Risk Factors Research Articles

Role of Environmental Risk Factors in the Etiology of Inflammatory Bowel Diseases: A Multicenter Study.

The increasing global incidence and prevalence of inflammatory bowel disease (IBD) necessitates an investigation into the potential influence of environmental risk factors on its origin. This multicenter case-control study aimed to investigate potential environmental risk factors contributing to IBD development in Turkey. The study included 156 Crohn's disease (CD), 277 ulcerative colitis (UC) patients, and 468 controls (matched for age and gender) from six hospitals' gastroenterology departments. Data collection relied on the International Organization of IBD's questionnaire on environmental factors. Each environmental factor was initially analyzed using univariate and subsequently multivariate logistic regression models. In the multivariate model, regular coffee consumption was associated with decreased odds for both CD (OR 0.28; 95% CI 0.14-0.55) and UC (OR 0.25; 95% CI 0.15-0.42). Stress was associated with UC (OR 3.27; 95% CI 1.76-6.10) and CD (OR 4.40; 95% CI 2.12-9.10) development. A history of childhood infectious diseases (gastroenteritis, upper respiratory tract infections, etc.) raised the odds for both CD (OR 9.45; 95% CI 2.51-35.6) and UC (OR 7.56; 95% CI 1.57-36.4). Conversely, consuming well/spring water (OR 0.22; 95% CI 0.10-0.50) and childhood antibiotic use (OR 0.41; 95% CI 0.18-0.93) showed a positive association against UC. Increased consumption of refined sugar and industrial food products emerged as risk factors for IBD. Smoking increased the risk for CD (OR 2.38; 95% CI 1.16-4.91), while ex-smoking increased the risk for UC (OR 3.16; 95% CI 1.19-8.37). This study represents the first multicenter case-control study in Turkey examining the effects of environmental factors on IBD. It revealed that coffee consumption is positively associated, while stress and childhood infection-related diseases are risk factors. These findings, which are not supported by other studies, provide insight into the relationships between these factors and IBD.

Transient Complete Asthenozoospermia

ABSTRACT Limited research exists on the mechanisms underlying asthenozoospermia associated with acquired ciliary dyskinesia. Primary ciliary dyskinesia links respiratory pathology with infertility and provides a basis for a potential mechanism. The aetiology of asthenozoospermia is often unclear and may be secondary to direct or indirect effects on sperm motility. Here, we report a case – with a brief clinical review – of recovering sperm motility after diagnosis of complete asthenozoospermia coinciding with resolution of chronic respiratory infections. The patient is a 36-year-old male, with initial semen analysis demonstrating 100% immotile sperm. Following the resolution of chronic respiratory infection, subsequent analysis demonstrated functional improvement with 76 million sperm/mL, 8% progressive motility and 4% strict morphology. Our case reinforces a potentially underappreciated role of environmental risk factors in infertility, with a focus on the patient’s history of infections and other risk factors for acquired ciliary dyskinesia, which should be kept in mind when treating patients with asthenozoospermia.

Meconium Concentrations of Pesticides and Risk of Hypospadias: A Case-Control Study in Brittany, France.

Hypospadias is a male genital tract defect for which an increase in prevalence has been documented over the last few decades. A role for environmental risk factors is suspected, including prenatal exposure to pesticides. To study the risk of hypospadias in association with multiple pesticide measurements in meconium samples. The Brittany Registry of Congenital Anomalies (France) conducted a case-control study between 2012 and 2018. Cases were hypospadias, ascertained by a pediatrician and a pediatric surgeon, excluding genetic conditions, following European Surveillance of Congenital Anomalies guidelines (N = 69). Controls (N = 135) were two male infants without congenital anomaly born after each case in the same maternity unit. Mothers in the maternity units completed a self-administered questionnaire, we collected medical data from hospital records, and medical staff collected meconium samples. We performed chemical analysis of 38 pesticides (parent compound and/or metabolite) by UHPLC/MS/MS following strict quality assurance/quality control criteria and blind to case-control status. We carried out logistic regression accounting for frequency-matching variables and major risk factors. Among the 38 pesticides measured, 16 (42%) were never detected in the meconium samples, 18 (47%) were in <5% of samples, and 4 (11%) in ≥5% of the samples. We observed an association between the detection of fenitrothion in meconium and the risk of hypospadias (OR = 2.6 [1.0-6.3] with n cases = 13, n controls = 21), but not the other pesticides. Our small study provides a robust assessment of fetal exposure. Fenitrothion's established antiandrogenic activities provide biologic plausibility for our observations. Further studies are needed to confirm this hypothesis.

Neighborhood deprivation and household socioeconomic status as risk factors for diabetes in Brussels

Abstract Background Socioeconomic (SE) differences in diabetes prevalence have been shown both at the individual and neighborhood level. Disentangling the role of SE determinants of diabetes at different levels can help to identify more targeted strategies to reduce SE differences in diabetes prevalence. As contextual factors may differ it is important to explore this in different settings. In this study we investigated the association of diabetes with household socioeconomic status (SES) and neighborhood deprivation in Brussels taking into account individual risk factors. Methods The study sample included participants ≥ 15 years of the Belgian National Health Interview Survey (HIS) 2013 and 2018 residing in Brussels (n = 5045). Information on neighborhood deprivation, assessed through a composite indicator (income, employment, nationality,..), was linked to the HIS data. A multilevel analysis was conducted to assess the association of self-reported diabetes with household SES and neighborhood deprivation adjusting for age, sex, obesity, nationality and country of birth. Results The overall prevalence of diabetes in the study sample was 6.8%. Individual risk factors associated with a higher diabetes prevalence were older age, obesity and being born outside the EU. Belonging to a household with a low income (OR 2.3;95% CI 1.2-2.5 - ref. highest income group), low education at household level (OR 1.6;95% CI 1.0-2.5 - ref. highest education group) and living in a deprived neighborhood (OR 2.0, 95%CI 1.3-3.1 - ref. living in wealthy area) were all independently associated with a higher diabetes prevalence. Conclusions Neighborhood deprivation and low household SES are independent risk factors of diabetes. Actions to reduce SE differences in diabetes prevalence should take into account determinants at the individual, household and neighborhood level. Further research should explore the role of environmental risk factors to explain the higher diabetes prevalence in deprived areas. Key messages • Differences in diabetes prevalence between rich and poor neighborhoods remain when accounting for individual characteristics and household socioeconomic status. • Environmental factors may explain the higher diabetes prevalence in deprived neighborhoods.

Groundwater constituents and the incidence of kidney cancer.

Kidney cancer incidence demonstrates significant geographic variation suggesting a role for environmental risk factors. This study sought to evaluate associations between groundwater exposures and kidney cancer incidence. The authors identified constituents from 18,506 public groundwater wells in all 58 California counties measured in 1996-2010, and obtained county-level kidney cancer incidence data from the California Cancer Registry for 2003-2017. The authors developed a water-wide association study (WWAS) platform using XWAS methodology. Three cohorts were created with 5 years of groundwater measurements and 5-year kidney cancer incidence data. The authors fit Poisson regression models in each cohort to estimate the association between county-level average constituent concentrations and kidney cancer, adjusting for known risk factors: sex, obesity, smoking prevalence, and socioeconomic status at the county level. Thirteen groundwater constituents met stringent WWAS criteria (a false discovery rate<0.10 in the first cohort, followed by p values<.05 in subsequent cohorts) and were associated with kidney cancer incidence. The seven constituents directly related to kidney cancer incidence (and corresponding standardized incidence ratios) were chlordane (1.06; 95% confidence interval [CI], 1.02-1.10), dieldrin (1.04; 95% CI, 1.01-1.07), 1,2-dichloropropane (1.04; 95% CI, 1.02-1.05), 2,4,5-TP (1.03; 95% CI, 1.01-1.05), glyphosate (1.02; 95% CI, 1.01-1.04), endothall (1.02; 95% CI, 1.01-1.03), and carbaryl (1.02; 95% CI, 1.01-1.03). Among the six constituents inversely related to kidney cancer incidence, the standardized incidence ratio furthest from the null was for bromide (0.97; 95% CI, 0.94-0.99). This study identified several groundwater constituents associated with kidney cancer. Public health efforts to reduce the burden of kidney cancer should consider groundwater constituents as environmental exposures that may be associated with the incidence of kidney cancer.

Environmental Risk Factors Contributing to the Transmission of COVID-19 in Zambia: A Cross-Sectional Study in Lusaka District

Background: A propagative increase in SARS-CoV-2 transmission has been witnessed in Zambia since the index case was reported in March 2020. Although sociocultural factors including movement patterns, people’s livelihood, and way of life have been demonstrated to influence SARS-CoV-2 transmission dynamics, the role of environmental risk factors has not been adequately documented. The aim of the study was to investigate environmental risk factors contributing to the transmission dynamics of SARS-CoV-2 in Zambia using a cross-sectional study Results: The positivity rates were 10.5 % cell phones, 5.3% door knobs, 2.7% remote controls and 2.6% beddings. All the other surfaces came out negative. The sex proportion of the respondents was 55% and 45% males and females respectively. Regarding occupancy density, 37.5% (15/40) resided in a 2 to 3-roomed house, 32.5% (13/40) resided in a 4 to 7 roomed house and 30% (12/40) resided in &gt; 7-roomed house. Of the 40 respondents, 75% (30/40) used recyclable face masks while 25% (10/40) used non-recyclable face masks. For the non-recyclable face masks, 30% of the respondents indicated incineration as a disposal method. A correlation coefficient of 0.25 was documented for the association between occupancy density and surface contamination. Conclusions: The study revealed that most environmental surfaces particularly mobile phones were rarely disinfected and were most likely to contribute to the transmission of SARS-CoV-2 in the community. Furthermore, the majority of the respondents used recyclable face masks which are easily washable. However, those who used non-recyclable face masks disposed of them indiscriminately which has the potential of contaminating the environment and further lead to the transmission of SARS-CoV-2.

Retrospective study of tumors from cattle slaughtered in Lombardy (Italy): preliminary evaluation on the establishment of a bovine cancer registry.

Forty‑one tumors were detected in a population of 1,649,003 cattle slaughtered in 4 abattoirs in Lombardy over a 5‑year period, for an overall prevalence of 2.5 tumors per 100,000 cattle. Tumors were classified according to the WHO histological classification of tumors of domestic animals. Alimentary and hemopoietic systems were commonly affected with 9 cases each. Other affected sites were the respiratory (n = 3), urinary (n = 2), endocrine (n = 2), musculoskeletal (n = 2), nervous (n = 1), and cardiovascular (n = 1) systems. The peritoneum was affected by 6 cases, while the primary location of 3 tumors of the connective tissues and 3 metastatic carcinomas was unidentified. Liver tumors and mesotheliomas, for which environmental risk factors are well‑known in humans, were common, as well as tumors typically encountered in pediatric human patients (tumors of mesenchymal tissues, pulmonary blastomas and nephroblastomas). These findings suggest the useful role of bovines as sentinel and model for human carcinogenesis. Our study indicates that the establishment of a bovine cancer registry in Lombardy is feasible considering its potential contribution to understanding the role of environmental risk factors in the genesis of tumors in animals and humans.

P339 A study of environmental risk factors in chronic rhinosinusitis

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM ObjectivesChronic rhinosinusitis (CRS) is a complex disease that incorporates many different conditions. Our aim is to determine the role of environmental risk factors in chronic rhinosinusitis.MethodsThis was a case-control study where forty cases of CRS in the age group of 18-62 years were recruited from the ENT-OPD of UCMS and GTB Hospital, Delhi, a tertiary care hospital, along with 40 age-appropriate healthy controls. Informed and written consent was obtained from all the subjects. Detailed history and examination along with routine blood and radiological investigations were done. Subjective assessment of disease was done using visual analog scales of SNOT 22 questionnaire, environmental questionnaire, and saccharine test. Objective assessment was done using endoscopic grading according to Lund and Kennedy scoring. CT scores were also obtained using Lund and Mackay staging system. Passive air sampling was done by the settle plate method and Anderson six-stage cascade impactor was used for active air sampling. Blood agar and Sabouraud dextrose agar plates were inserted on the six stages of the cascade impactor, which were later incubated at 35°C and 25°C respectively, for 18-24 hours. Bioaerosol concentrations were calculated and MicroScan WalkAway system was used to identify bacterial and fungal growth. The correlation between total bioaerosol concentration and the symptom score was done by spearman's correlation coefficient; a comparison of mean total bioaerosol concentration between the case and control groups was done by Mann-Whitney U-test.ResultsThe mean total bio-aerosol concentration from active air sampling in the case group was 458.52 CFU/m3 and 437.63 CFU/m3 in control, which was not significant. It was found to be negatively correlated, but not significant with various parameters in case groups like SNOT 22 score, environmental exposure score, saccharine test, smoking, and endoscopic score. A positive but insignificant correlation was found between total bioaerosol concentration and absolute eosinophilic count and CT score. The mean CFU/100 mm3 counted after passive air sampling between case and control group was 34.03 and 30.88 CFU/100mm3 which was not significant. Fungal growths were mostly Aspergillus flavus and A. Niger followed by Cladosporium spp.ConclusionThe fungal burden was high in all the households of the case as well as control groups, although, a significant correlation could not be established. The environmental conditions found in this study were found to be conducive to future risk of exacerbation of preexisting fungal infections for which, indoor air quality needs to be monitored.

The association between dietary total antioxidant capacity and NMO-IgG seropositivity in patients with neuromyelitis optica spectrum disorder

ObjectivesThere is growing evidence highlighting the role of environmental risk factors of NMO-IgG seropositivity in patients with neuromyelitis optica spectrum disorder (NMOSD). The present study investigated the possible association between dietary total antioxidant capacity (TAC) and NMO-IgG seropositivity in NMOSD patients. MethodsFifty-six patients with a definite diagnosis of NMOSD were included in the study. Data on patients’ age, gender, height, weight, cigarette smoking status, and alcohol consumption were collected and recorded. Body mass index (BMI) was also calculated. In addition, dietary habits of patients were evaluated using an adjusted semi-quantitative food frequency questionnaire (FFQ) that consists of 168 food items. Dietary TAC was calculated using the oxygen radical absorption capacity (ORAC) method. Enzyme-linked immunosorbent assay (ELISA) method was used to determine the NMO-IgG serum status. The association between dietary TAC and odds of NMO-IgG seropositivity was measured using the logistic regression analysis. ResultsThe mean of dietary TAC was 8362.8 (μmolTE/1000 kcal) in seronegative patients and 6609.9 (μmolTE/1000 kcal) in seropositive patients and had a significant difference between the mentioned groups of patients (P: 0.02). An inverse association was found between dietary TAC and odds of NMO-IgG seropositivity in all three regression models. The higher dietary intake of antioxidant resulted in significant findings as follows: 92% (95% CI: 0.01–0.53), 97% (95% CI: 0.00–0.34), and 97% (95% CI: 0.00–0.32) lower odds of NMO-IgG seropositivity in the fourth quartiles of the first, the second, and the third regression model, respectively. Moreover, the inverse association between fruit intake and odds of NMO-IgG seropositivity was significant in the third quartile (OR:0.10; 95%CI: 0.01–0.97). ConclusionThe present study indicated a significant inverse association between dietary TAC and NMO-IgG seropositivity of NMOSD patients. As no definite treatment can be offered for NMOSD and nutrition is a modifiable factor in this regard, specification of dietary factors affecting the risk of NMOSD is of great value.

The Role of Environmental Risk Factors on the Development of Childhood Allergic Rhinitis.

Environmental factors play an important role in the development and exacerbation of allergic rhinitis (AR) in childhood. Indoor air pollution, such as house dust mites and secondhand smoke, can significantly increase the onset of AR, while pet dander may affect the exacerbation of AR symptoms in children. Furthermore, traffic related air pollution and pollen are outdoor air pollutants that can affect immune competency and airway responsiveness, increasing the risk of AR in children. Climate change has increased AR in children, as growth patterns of allergenic species have changed, resulting in longer pollen seasons. More extreme and frequent weather events also contribute to the deterioration of indoor air quality due to climate change. Additionally, viruses provoke respiratory tract infections, worsening the symptoms of AR, while viral infections alter the immune system. Although viruses and pollution influence development and exacerbation of AR, a variety of treatment and prevention options are available for AR patients. The protective influence of vegetation (greenness) is heavily associated with air pollution mitigation, relieving AR exacerbations, while the use of air filters can reduce allergic triggers. Oral antihistamines and intranasal corticosteroids are common pharmacotherapy for AR symptoms. In this review, we discuss the environmental risk factors for AR and summarize treatment strategies for preventing and managing AR in children.

Environmental Risk Factors for Bipolar Disorders and High-Risk States in Adolescence: A Systematic Review.

Background and objectives: A deeper comprehension of the role that environmental risk factors play in the development of adolescent Bipolar Disorder (BD), as well as in the evolution of high-risk states for BD, may entangle further prevention and treatment advances. The present systematic review is aimed at critically summarizing evidence about the role that environmental risk factors play in the development of BD in adolescence and their interaction with BD high-risk states. Materials and Methods: MEDLINE/Pubmed, Scopus and Web of Science datasets were systematically searched until 4 September 2020. Original studies that reported information about the role of environmental risk factors in the development of BD during adolescence, or assessing their influence on the development of psychopathology in high-risk states for BD, were considered for inclusion. Two blind researchers performed title/abstract, full-text screening, and hand-screening of relevant references. The risk of bias was assessed by means of the Newcastle-Ottawa Scale. Results: Fourteen studies were included in the review. Negative stressful life events, particularly sexual and physical abuse, but also emotional mistreatment, were associated with more severe psychopathology in adolescents with BD, as well as with higher risk for developing mood disorders in BD offspring. Similar findings were detected for familial environment-related features, such as parental rejection and low perceived care, while no univocal results were found when analyzing familial functioning. Conclusions: The present systematic review confirmed the relevant role that environmental risk factors, particularly negative stressful live events and family-related features, play in the development of BD psychopathology during adolescence. Future studies are expected to clarify possible further environmental factors that may be implicated in the development of BD during youth that may serve as target of prevention and early treatment strategies.

Environmental Risk Factors for Early-Onset Alzheimer's Dementia and Frontotemporal Dementia: A Case-Control Study in Northern Italy.

Background: Early-onset dementia (EOD) is defined as dementia with symptom onset before 65 years. The role of environmental risk factors in the etiology of EOD is still undefined. We aimed at assessing the role of environmental risk factors in EOD etiology, taking into account its different clinical types. Methods: Using a case-control study, we recruited all EOD cases referred to Modena hospitals from 2016 to 2019, while the referent population was drawn from cases’ caregivers. We investigated residential history, occupational and environmental exposures to chemicals and lifestyle behaviors through a self-administered questionnaire. We computed the odds ratios of EOD risk (overall and restricting to the Alzheimer’s dementia (AD) or frontotemporal dementia (FTD) diagnoses) and the corresponding 95% confidence intervals using an unconditional logistic regression model. Results: Fifty-eight EOD patients (19 FTD and 32 AD) and 54 controls agreed to participate. Most of the investigated exposures, such as occupational exposure to aluminum, pesticides, dyes, paints or thinners, were associated with an increased odds ratio (OR) for FTD but not for AD. Long-term use of selenium-containing dietary supplements was associated with increased OR for EOD and, particularly, for FTD. For both EOD forms, smoking and playing football showed an increased odds ratio, while cycling was associated with increased risk only in FTD. Overall sports practice appeared to be a protective factor for both types. Conclusions: Our results suggest a role of environmental and behavioral risk factors such as some chemical exposures and professional sports in EOD etiology, in particular with reference to FTD. Overall sports practice may be associated with a reduced EOD risk.

Environmental and occupational risk factors for early onset dementia in an Italian community

Background: Early onset dementia (EOD) is defined as dementia with symptoms onset before 65 years. Little is known about the etiological role of environmental and occupational risk factors. We aimed at assessing the role of these factors in disease etiology. Methods: Using a case-control design, we recruited all EOD cases resident in Modena province from October, 2016 to October, 2019, as well as a referent population drawn from patients’ care-givers. We investigated residential history of study participants, and their occupational and environmental exposures to pesticides, solvents and metals through a self-administered questionnaire. We computed the odds ratios (ORs) of disease risk, and the corresponding 95% confidence intervals (CIs), according to exposure to the investigated risk factors, using an unconditional logistic regression model adjusted for sex, age, and education. Results: Fifty-eight EOD cases and fifty-four controls agreed to participate. Among occupational factors, disease risk was associated with exposure to aluminum (OR 2.6, 95% CI 0.4-15.7), pesticides (OR 2.3, 95% CI 0.7-7.8) particularly from agricultural occupational exposure (OR 3.1, 95% CI 0.7-13.3) and dyes, paints or thinners (OR 1.7, 95% CI 0.6-5.0). Among lifestyles factors, smoking (OR 1.3, 95% CI 0.6-2.9) and playing football (OR 2.2, 95% CI 0.5-9.3) or cycling (OR 2.3, 95% CI 0.4-13.4) were associated with higher EOD risk, although overall sports practice appeared to be protective factor (OR 0.4, 95% CI 0.2-0.9). Risk was also positively associated with history of head trauma (OR 1.2, 95% CI 0.3-4.1) and particularly upper arm trauma (OR 2.2, 95% CI 0.7-7.5), but not overall trauma. No association emerged for exposure to electromagnetic fields. Conclusions: Despite the study limitations, our results appear to support a role of environmental risk factors in EOD etiology, particularly of some chemical exposures and professional sports, while overall sports practice may have a beneficial effect.

Orbital disease in neuro-ophthalmology.

Orbital disease represents a diverse spectrum of pathology and can result in a variety of neuro-ophthalmic manifestations. The aim of this review is to provide updates on recent advances in our understanding of orbital disease secondary to thyroid eye disease, myositis, IgG4-related disease, sarcoidosis, granulomatosis with polyangiitis and various tumours. With regards to thyroid eye disease, there have been recent advances in the development of steroid-sparing therapies, new modalities for objectively monitoring disease activity and increased understanding of the role of environmental risk factors. There has been interest in characterizing the clinical course and underlying mechanism of optic nerve disease secondary to orbital disorders, which has led to advances in how we monitor for and prevent permanent vision loss. Increased knowledge of orbital tumour subtype histopathology and the development of novel classification systems has had prognostic value and aided medical decision-making. Orbital disease occurs secondary to a wide variety of diseases and can lead to neuro-ophthalmic manifestations with significant morbidity. Advances in our understanding of different subtypes of orbital disease have improved our ability to treat these potentially debilitating conditions.

Dermatophytosis among Ruminants in Egypt: The Infection Rate, Identification and Comparison between Microscopic, Cultural and Molecular Methods

Dermatophytosis is a skin disease of farm animals caused by different species of the Microsporum and Trichophyton genera. Although the disease is self-limiting, ringworm has a major public and veterinary health problem with worldwide distribution including Egypt. The objectives of this study were to estimate the infection rate of dermatophytosis in ruminants, identify the incriminated dermatophyte species and differentiate among them using conventional and molecular methods. Moreover, assessment of the role of environmental risk factors in the occurrence of the disease. Cow (n=197), sheep (n=103) and goats (n=70) of different breeds, sexes, and ages in Sharkia and Dakahalia Governorates were clinically examined during the period from June 2018 to July 2019. Out of the examined animals, 111 (30%) have skin lesions consistent with dermatophytosis. The infection rate of the disease was 30, 37.9 and 18.6% in cow, sheep and goat, respectively. The rate of infection was higher in the Holstein breed (36.6%) compared to native breed (23%). The higher rate of infection was found amongst lambs less than 6 months while in cow and goats the infection rate was higher in animals more than 6 months old. Male animals were generally more infected than females in all studied animals, and the infection was more common in winter season. Trichophyton verrucosum was the most commonly identified dermatophyte species (25.6%). Polymerase chain reaction (PCR) of internal transcribed spacer (ITS) along with restriction fragment length polymorphism method (RFLP) succeeded to differentiate between both isolated Trichophyton and Microsporum species. In conclusion, PCR along with culture results acted as gold standard methods for diagnosis of dermatophytosis. Restriction Fragment Length Polymorphism method was considered as a rapid approach with high specificity and sensitivity to identify and differentiate dermatophytes in ruminants.

T170. GENE AND ENVIRONMENT INTERPLAY AMONG DIAGNOSTIC CATEGORIES IN THE EUGEI STUDY

BackgroundThe importance of inherited factors in the development of affective psychosis, which includes bipolar disorder and major depression disorder, is widely accepted, but the fact that monozygotic twin concordance is substantially less than 100% suggests that environmental factors (ERF) are likely to play an important role as well. While the link between a variety of ERF and schizophrenia-spectrum disorder is well established, less is known about how these ERF impact in affective psychosis. In the current study we aim to analyse the role of environmental risk factors in the expression of affective disorder compared with schizophrenia-spectrum disorder, and its interaction with the genetic risk by using polygenic risk score (PRS).MethodsDNA was obtained from most participants (73.6% of 1130 cases and 78.5% of 1499 controls) among 16 European cities as part of the EUGEI case-control study. PRS for SZ, BD and MDD were built using the latest available data from the Psychiatric Genomic Consortium (PGC). Multinomial logistic regression models were used to test whether the association of genetic load (by PRSs) with different diagnostic categories based on DSMIV from OPCRIT items were greater if there was also evidence of ERF (urbanicity, migration, cannabis use and childhood trauma) through the inclusion of interaction terms between the different PRSs and the ERF. Analyses were conducted for each environmental factor separately and for a combined poly-environmental risk score based on Maudsley Environmental Score (MPES) will be calculated.ResultsBeing 1st generation migrant was not associated with any of the diagnostic categories, nor independently nor in interaction with PRSs. Living in urban environment increases the risk of SSD (RRR=1.68, 95% CI 1.06 – 2.67), but without interacting with any genetic measure. Regarding cannabis use, having ever used cannabis is independently significantly associated with SSD (RRR=2.26, 95% CI 1.69 – 3.02) and BD (RRR=5.3, 95% CI 2.69 – 10.46), showing as well in the latter group an interaction with PRS MDD (RRR=2.3, 95% CI 1.18 – 4.49). Although daily use of cannabis strongly predicted risk of SSD and BD, having use more than once a week only increased risk for SSD. Neither having used cannabis more than once a week or daily interacted with any of the PRSs. Having been exposed to any childhood trauma was independently significantly associated with all three diagnostic groups, but did not show any significant interaction with PRSs. Lastly, despite MPES increased risk for SSD and BD, it didn’t interact significantly with any PRSs.DiscussionThese results suggest that despite evidence of both PRSs on one hand and urbanicity, cannabis and childhood trauma overall increase risk of belonging to any psychotic diagnostic category separately, we only found some suggestion of potential interaction between genetic vulnerability to MDD and cannabis use associated with BD. Nonetheless, due to most of the interactions showing the expected trend, analyses examining interactions between PRSs and ERF with the different diagnostic groups with bigger samples are warranted.

OP07 The epidemiology of inflammatory bowel diseases among immigrants to Denmark: A population-based cohort study

Abstract Background The incidence of inflammatory bowel diseases (IBDs) among immigrants and in countries with historically low IBD risk is rising, implicating environmental risk factors in IBD pathogenesis. The purpose of our study was to determine the incidence rates of Crohn’s disease (CD) and ulcerative colitis (UC), among immigrants to Denmark, a high IBD incidence country, according to the country of birth and age at immigration, in comparison with the corresponding incidence rates in the Danish host population. Methods Using the Danish Civil Registration System, we identified all residents in Denmark with a known country of birth between January 1977 and December 2018. First-generation immigrants were persons who, along with parents, were born outside Denmark; second-generation immigrants were Danish-born persons whose parents were born outside Denmark. We recorded immigrants’ (or parents’) country of birth, age at immigration and duration of stay in Denmark. Study participants were followed for CD and UC diagnosis in the Danish National Patient Registry. Incidence rate ratios (IRRs) according to immigration status were estimated using log-linear Poisson regression analysis, and stratified by IBD prevalence in the country of birth (low, intermediate and high), and among first-generation immigrants, by age at immigration and duration of stay in Denmark. Results In this cohort of 9,038,025 subjects, among 1,295,518 first-generation and 208,826 second-generation immigrants eligible for inclusion, 4,805 first-generation and 898 second-generation immigrants were diagnosed with CD or UC. The risk of IBD among first-generation immigrants reflected risk in the country of birth (low, intermediate or high, Table 1), and increased with &amp;gt;20 years stay in Denmark (Table 2). Among second-generation immigrants, the risk of CD and UC was comparable to that in Danish natives (Table 1). Younger age at immigration did not impact IBD risk. Conclusion In this population-based study, the risk of IBD among first-generation immigrants reflected that in their country of birth, and increased with &amp;gt;20 years stay in Denmark. Among second-generation immigrants, the risk was comparable to native Danes. These findings underscore the role of environmental risk factors in the aetiology of IBD. Further studies to determine risk factors for IBD among immigrants to Denmark are ongoing.

Metabolomic and metallomic profile differences between Veterans and Civilians with Pulmonary Sarcoidosis

Sarcoidosis is a disorder characterized by granulomatous inflammation of unclear etiology. In this study we evaluated whether veterans with sarcoidosis exhibited different plasma metabolomic and metallomic profiles compared with civilians with sarcoidosis. A case control study was performed on veteran and civilian patients with confirmed sarcoidosis. Proton nuclear magnetic resonance spectroscopy (1H NMR), hydrophilic interaction liquid chromatography mass spectrometry (HILIC-MS) and inductively coupled plasma mass spectrometry (ICP-MS) were applied to quantify metabolites and metal elements in plasma samples. Our results revealed that the veterans with sarcoidosis significantly differed from civilians, according to metabolic and metallomics profiles. Moreover, the results showed that veterans with sarcoidosis and veterans with COPD were similar to each other in metabolomics and metallomics profiles. This study suggests the important role of environmental risk factors in the development of different molecular phenotypic responses of sarcoidosis. In addition, this study suggests that sarcoidosis in veterans may be an occupational disease.

A model of human endogenous retrovirus (HERV) activation in mental health and illness

Despite strong evidence for the heritability of major depressive disorder (MDD), efforts to identify causal genes have been disappointing. Furthermore, although there is strong support for life stress as a major predictor of MDD, there are also considerable individual differences in susceptibility and resilience that remain poorly understood. Efforts to identify specific gene-by-environment risk factors produced results that were initially encouraging, but that were not supported by later large-scale studies. Here I propose a novel mechanism that could address the “missing heritability” of MDD, the role of environmental risk factors, and individual differences in susceptibility and resilience. This mechanism focuses on a class of transposable elements, Human Endogenous Retroviruses (HERVs), which make up approximately 8% of the human genome as the result of ancient retroviral infections that entered mammalian germ lines throughout the course of evolution. My primary hypothesis is that exposure to either exogenous viruses or traumatic experiences can activate HERVs in the brain to cause depressive (and possibly other psychiatric) symptoms. My secondary hypothesis is that individual differences in vulnerability or resilience result from the balance of activated HERVs with pathogenic versus protective functions in the brain. Future research can test these hypotheses by analysis of postmortem human brain tissue from donors with known viral or trauma histories; animal studies manipulating HERV expression; cell culture studies examining regulatory mechanisms of HERV expression; and from brain imaging studies of individuals with known HERV-expression. Such research may reveal novel functions of HERVs in neural tissue and may lead to a new generation of psychiatric interventions designed to target aberrant HERV activation.

Discrimination of indoor versus outdoor environmental state with machine learning algorithms in myopia observational studies

BackgroundWearable smart watches provide large amount of real-time data on the environmental state of the users and are useful to determine risk factors for onset and progression of myopia. We aim to evaluate the efficacy of machine learning algorithm in differentiating indoor and outdoor locations as collected by use of smart watches.MethodsReal time data on luminance, ultraviolet light levels and number of steps obtained with smart watches from dataset A: 12 adults from 8 scenes and manually recorded true locations. 70% of data was considered training set and support vector machine (SVM) algorithm generated using the variables to create a classification system. Data collected manually by the adults was the reference. The algorithm was used for predicting the location of the remaining 30% of dataset A. Accuracy was defined as the number of correct predictions divided by all. Similarly, data was corrected from dataset B: 172 children from 3 schools and 12 supervisors recorded true locations. Data collected by the supervisors was the reference. SVM model trained from dataset A was used to predict the location of dataset B for validation. Finally, we predicted the location of dataset B using the SVM model self-trained from dataset B. We repeated these three predictions with traditional univariate threshold segmentation method.ResultsIn both datasets, SVM outperformed the univariate threshold segmentation method. In dataset A, the accuracy and AUC of SVM were 99.55% and 0.99 as compared to 95.11% and 0.95 with the univariate threshold segmentation (p < 0.01). In validation, the accuracy and AUC of SVM were 82.67% and 0.90 compared to 80.88% and 0.85 with the univariate threshold segmentation method (p < 0.01). In dataset B, the accuracy and AUC of SVM and AUC were 92.43% and 0.96 compared to 80.88% and 0.85 with the univariate threshold segmentation (p < 0.01).ConclusionsMachine learning algorithm allows for discrimination of outdoor versus indoor environments with high accuracy and provides an opportunity to study and determine the role of environmental risk factors in onset and progression of myopia. The accuracy of machine learning algorithm could be improved if the model is trained with the dataset itself.