Non-genetic Risk Factors Research Articles

The interaction between early life complications and a polygenic risk score for schizophrenia is associated with brain activity during emotion processing in healthy participants.

Previous evidence suggests that early life complications (ELCs) interact with polygenic risk for schizophrenia (SCZ) in increasing risk for the disease. However, no studies have investigated this interaction on neurobiological phenotypes. Among those, anomalous emotion-related brain activity has been reported in SCZ, even if evidence of its link with SCZ-related genetic risk is not solid. Indeed, it is possible this relationship is influenced by non-genetic risk factors. Thus, this study investigated the interaction between SCZ-related polygenic risk and ELCs on emotion-related brain activity. 169 healthy participants (HP) in a discovery and 113 HP in a replication sample underwent functional magnetic resonance imaging (fMRI) during emotion processing, were categorized for history of ELCs and genome-wide genotyped. Polygenic risk scores (PRSs) were computed using SCZ-associated variants considering the most recent genome-wide association study. Furthermore, 75 patients with SCZ also underwent fMRI during emotion processing to verify consistency of their brain activity patterns with those associated with risk factors for SCZ in HP. Results in the discovery and replication samples indicated no effect of PRSs, but an interaction between PRS and ELCs in left ventrolateral prefrontal cortex (VLPFC), where the greater the activity, the greater PRS only in presence of ELCs. Moreover, SCZ had greater VLPFC response than HP. These results suggest that emotion-related VLPFC response lies in the path from genetic and non-genetic risk factors to the clinical presentation of SCZ, and may implicate an updated concept of intermediate phenotype considering early non-genetic factors of risk for SCZ.

Asian Cohort for Alzheimer Disease (ACAD) Pilot Study: Vietnamese Americans.

The objective of this pilot study was to establish the feasibility of recruiting older Vietnamese Americans for research addressing genetic and nongenetic risk factors for Alzheimer disease (AD). Twenty-six Vietnamese Americans were recruited from communities in San Diego. A Community Advisory Board provided cultural and linguistic advice. Bilingual/bicultural staff measured neuropsychological, neuropsychiatric, lifestyle, and medical/neurological functioning remotely. Saliva samples allowed DNA extraction. A consensus team reviewed clinical data to determine a diagnosis of normal control (NC), mild cognitive impairment (MCI), or dementia. Exploratory analyses addressed AD risk by measuring subjective cognitive complaints (SCC), depression, and vascular risk factors (VRFs). Twenty-five participants completed the study (mean age=73.8y). Eighty percent chose to communicate in Vietnamese. Referrals came primarily from word of mouth within Vietnamese communities. Diagnoses included 18 NC, 3 MCI, and 4 dementia. Participants reporting SCC acknowledged more depressive symptoms and had greater objective cognitive difficulty than those without SCC. Eighty-eight percent of participants reported at least 1 VRF. This pilot study supports the feasibility of conducting community-based research in older Vietnamese Americans. Challenges included developing linguistically and culturally appropriate cognitive and neuropsychiatric assessment tools. Exploratory analyses addressing nongenetic AD risk factors suggest topics for future study.

Meta-analysis of ACE inhibitor–induced angioedema identifies novel risk locus

Angioedema is a rare but potentially life-threatening adverse drug reaction in patients receiving angiotensin-converting enzyme inhibitors (ACEis). Research suggests that susceptibility to ACEi-induced angioedema (ACEi-AE) involves both genetic and nongenetic risk factors. Genome- and exome-wide studies of ACEi-AE have identified the first genetic risk loci. However, understanding of the underlying pathophysiology remains limited. We sought to identify further genetic factors of ACEi-AE to eventually gain a deeper understanding of its pathophysiology. By combining data from 8 cohorts, a genome-wide association study meta-analysis was performed in more than 1000 European patients with ACEi-AE. Secondary bioinformatic analyses were conducted to fine-map associated loci, identify relevant genes and pathways, and assess the genetic overlap between ACEi-AE and other traits. Finally, an exploratory cross-ancestry analysis was performed to assess shared genetic factors in European and African-American patients with ACEi-AE. Three genome-wide significant risk loci were identified. One of these, located on chromosome 20q11.22, has not been implicated previously in ACEi-AE. Integrative secondary analyses highlighted previously reported genes (BDKRB2 [bradykinin receptor B2] and F5 [coagulation factor 5]) as well as biologically plausible novel candidate genes (PROCR [protein C receptor] and EDEM2 [endoplasmic reticulum degradation enhancing alpha-mannosidase like protein 2]). Lead variants at the risk loci were found with similar effect sizes and directions in an African-American cohort. The present results contributed to a deeper understanding of the pathophysiology of ACEi-AE by (1) providing further evidence for the involvement of bradykinin signaling and coagulation pathways and (2) suggesting, for the first time, the involvement of the fibrinolysis pathway in this adverse drug reaction. An exploratory cross-ancestry comparison implicated the relevance of the associated risk loci across diverse ancestries.

A post hoc analysis of previously untreated patients with severe hemophilia A who developed inhibitors in the PUPs A-LONG trial

AbstractInhibitor development is a major therapeutic complication for people with hemophilia. The phase 3 PUPs A-LONG study evaluated the safety and efficacy of efmoroctocog alfa (a recombinant factor VIII Fc fusion protein, herein referred to as rFVIIIFc) in previously untreated patients (PUPs) with severe hemophilia A. Male PUPs <6 years old were enrolled and received rFVIIIFc; inhibitor development was the primary end point. Post hoc analyses, including patient treatment regimen patterns and timing of inhibitor development, descriptive and Kaplan-Meier analyses of time to first inhibitor-positive test by treatment regimen and by titer, and consumption, were performed to describe patients who developed inhibitors during PUPs A-LONG. We investigated patient characteristics (eg, demographics and genotype) and nongenetic risk factors (eg, intense factor exposure and central venous access device [CVAD] placement) that may predict inhibitor development and characteristics of inhibitor development (low-titer vs high-titer inhibitor). Baseline characteristics were similarly distributed for age, race, and ethnicity across both patients who were inhibitor-positive and those who were inhibitor-negative (all P > .05). High-risk F8 variants were associated with development of high-titer inhibitors (P = .028). High-titer inhibitor development was often preceded by the presence of a low-titer inhibitor. Patients whose low-titer inhibitor progressed to a high-titer inhibitor received a higher mean dose per infusion (98.4 IU/kg, n = 5) compared with those whose low-titer inhibitor resolved spontaneously (59.2 IU/kg, n = 7; P = .033) or persisted (45.0 IU/kg, n = 5; P = .047). There was no association between CVAD placement surgery and inhibitor development. Post hoc analyses suggest that F8 genotype and dose of factor are as important as inhibitor risk factors and require further investigation. This study was registered at ClinicalTrials.gov as #NCT02234323.

Racial and Ethnic Differences in the Population-Attributable Fractions of Alzheimer Disease and Related Dementias.

Previous studies estimated that modifiable risk factors explain up to 40% of the dementia cases in the United States and that this population-attributable fraction (PAF) differs by race and ethnicity-estimates of future impact based on the risk factor prevalence in contemporary surveys. The aim of this study was to determine the race-specific and ethnicity-specific PAF of late-onset Alzheimer disease and related dementias (ADRDs) based on the risk factor prevalence and associations observed on the same individuals within a prospective cohort. Data were from Multiethnic Cohort Study participants (African American, Japanese American, Latino, Native Hawaiian, and White) enrolled in Medicare Fee-for-Service. We estimated the PAF based on the prevalence of risk factors at cohort baseline and their mutually adjusted association with subsequent ADRD incidence. Risk factors included low educational attainment and midlife exposures to low neighborhood socioeconomic status, unmarried status, history of hypertension, stroke, diabetes or heart disease, smoking, physical inactivity, short or long sleep duration, obesity, and low-quality diet, as well as APOE ε4 for a subset. Among 91,881 participants (mean age 59.3 at baseline, 55.0% female participants), 16,507 incident ADRD cases were identified from Medicare claims (1999-2016, mean follow-up 9.3 years). The PAF for nongenetic factors combined was similar in men (24.0% [95% CI 21.3-26.6]) and women (22.8% [20.3-25.2]) but varied across Japanese American (14.2% [11.1-17.2]), White (21.9% [19.0-24.7]), African American (27.8% [22.3-33.0]), Native Hawaiian (29.3% [21.0-36.7]), and Latino (33.3% [27.5-38.5]) groups. The combined PAF was attenuated when accounting for competing risk of death, in both men (10.4%) and women (13.9%) and across racial and ethnic groups (4.7%-25.5%). The combined PAF was also different by age at diagnosis and ADRD subtypes, higher for younger (65-74 years: 43.2%) than older (75-84 years: 32.4%; ≥85 years: 11.3%) diagnoses and higher for vascular or unspecified ADRD than for AD or Lewy body dementia. An additional PAF of 11.8% (9.9-13.6) was associated with APOE ε4, which together with nongenetic risk factors accounted for 30.6% (25.8-35.1) of ADRD. Known risk factors explained about a third of the ADRD cases but with unequal distributions across racial and ethnic groups.

Asian Cohort for Alzheimer's Disease (ACAD) pilot study on genetic and non-genetic risk factors for Alzheimer's disease among Asian Americans and Canadians.

Clinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population. The ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites. We developed a comprehensive study protocol for outreach and recruitment, an extensive data collection packet, and a centralized data management system, in English, Chinese, Korean, and Vietnamese. ACAD has recruited 606 participants with an additional 900 expressing interest in enrollment since program inception. ACAD's traction indicates the feasibility of recruiting Asians for clinical research to enhance understanding of AD risk factors. ACAD will recruit>5000 participants to identify genetic and non-genetic/lifestyle AD risk factors, establish blood biomarker levels for AD diagnosis, and facilitate clinical trial readiness. The Asian Cohort for Alzheimer's Disease (ACAD) promotes awareness of under-investment in clinical research for Asians. We are recruiting Asian Americans and Canadians for novel insights into Alzheimer's disease. We describe culturally appropriate recruitment strategies and data collection protocol. ACAD addresses challenges of recruitment from heterogeneous Asian subcommunities. We aim to implement a successful recruitment program that enrolls across three Asian subcommunities.

Genome-wide polygenic risk scores for colorectal cancer have implications for risk-based screening.

Hereditary factors, including single genetic variants and family history, can be used for targeting colorectal cancer (CRC) screening, but limited data exist on the impact of polygenic risk scores (PRS) on risk-based CRC screening. Using longitudinal health and genomics data on 453,733 Finnish individuals including 8801 CRC cases, we estimated the impact of a genome-wide CRC PRS on CRC screening initiation age through population-calibrated incidence estimation over the life course in men and women. Compared to the cumulative incidence of CRC at age 60 in Finland (the current age for starting screening in Finland), a comparable cumulative incidence was reached 5 and 11 years earlier in persons with high PRS (80-99% and >99%, respectively), while those with a low PRS (< 20%) reached comparable incidence 7 years later. The PRS was associated with increased risk of post-colonoscopy CRC after negative colonoscopy (hazard ratio 1.76 per PRS SD, 95% CI 1.54-2.01). Moreover, the PRS predicted colorectal adenoma incidence and improved incident CRC risk prediction over non-genetic risk factors. Our findings demonstrate that a CRC PRS can be used for risk stratification of CRC, with further research needed to optimally integrate the PRS into risk-based screening.

Risk factors associated with age at onset of Parkinson’s disease in the UK Biobank

Substantial evidence shown that the age at onset (AAO) of Parkinson’s disease (PD) is a major determinant of clinical heterogeneity. However, the mechanisms underlying heterogeneity in the AAO remain unclear. To investigate the risk factors with the AAO of PD, a total of 3156 patients with PD from the UK Biobank were included in this study. We evaluated the effects of polygenic risk scores (PRS), nongenetic risk factors, and their interaction on the AAO using Mann–Whitney U tests and regression analyses. We further identified the genes interacting with nongenetic risk factors for the AAO using genome-wide environment interaction studies. We newly found physical activity (P < 0.0001) was positively associated with AAO and excessive daytime sleepiness (P < 0.0001) was negatively associated with AAO, and reproduced the positive associations of smoking and non-steroidal anti-inflammatory drug intake and the negative association of family history with AAO. In the dose-dependent analyses, smoking duration (P = 1.95 × 10−6), coffee consumption (P = 0.0150), and tea consumption (P = 0.0008) were positively associated with AAO. Individuals with higher PRS had younger AAO (P = 3.91 × 10−5). In addition, we observed a significant interaction between the PRS and smoking for AAO (P = 0.0316). Specifically, several genes, including ANGPT1 (P = 7.17 × 10−7) and PLEKHA6 (P = 4.87 × 10−6), may influence the positive relationship between smoking and AAO. Our data suggests that genetic and nongenetic risk factors are associated with the AAO of PD and that there is an interaction between the two.

Deregulation of the Glymphatic System in Alzheimer's Disease: Genetic and Non-Genetic Factors.

Alzheimer's disease (AD) is the most prevalent form of dementia and is characterized by progressive degeneration of brain function. AD gradually affects the parts of the brain that control thoughts, language, behavior and mental function, severely impacting a person's ability to carry out daily activities and ultimately leading to death. The accumulation of extracellular amyloid-β peptide (Aβ) and the aggregation of intracellular hyperphosphorylated tau are the two key pathological hallmarks of AD. AD is a complex condition that involves both non-genetic risk factors (35%) and genetic risk factors (58-79%). The glymphatic system plays an essential role in clearing metabolic waste, transporting tissue fluid, and participating in the immune response. Both non-genetic and genetic risk factors affect the glymphatic system to varying degrees. The main purpose of this review is to summarize the underlying mechanisms involved in the deregulation of the glymphatic system during the progression of AD, especially concerning the diverse contributions of non-genetic and genetic risk factors. In the future, new targets and interventions that modulate these interrelated mechanisms will be beneficial for the prevention and treatment of AD.

Assessing Long-Term Non-Genetic Risk Factors for Breast Cancer

Assessing Long-Term Non-Genetic Risk Factors for Breast Cancer

Characteristics of body mass index and sodium intake of adults with hypertension family history in Yogyakarta

Hypertension is a progression of prehypertension due to the accumulation of several non-genetic risk factors (environmental factors) that occur together (common underlying risk factors) or genetic factors or the interaction between the two. Risk factors for hypertension that can be controlled include high sodium intake, lack of physical activity, obesity, smoking, and alcohol consumption, while risk factors that cannot be controlled include increasing age, gender, and a family or genetic history of hypertension. This study aimed to determine the characteristics of Body Mass Index (BMI) and sodium intake in adults with a family history of hypertension in Yogyakarta. This study used a case-control design. Subjects studied were healthy individuals with a family history of hypertension as case subjects (n = 42), and control subjects were individuals without a family history of hypertension (n = 41). Body mass index (BMI) was measured with anthropometry, and sodium intake was measured using a quantitative food frequency questionnaire. Independent Sample T-test and Chi-Square test analyzed the data with a significance level of p &lt; 0.05. The average BMI and sodium intake are higher in the case group than in the control group. There was no significant association between BMI and sodium intake and risk factors of hypertension (p&gt;0.05). Body mass index and sodium intake in the case and control group were not significant differences (p&gt;0.05). The BMI values and sodium intake levels were higher in the group of individuals with a family history of hypertension compared to those without a family history of hypertension, but not statistically significant.

Non-Genetic Factors in Schizophrenia in Yemen

Background and objective: The way we think about schizophrenia today is profoundly different from the way this illness was seen in the twentieth century. We now know that the etiology of schizophrenia is multifactorial and reflects an interaction between genetic vulnerability and environmental contributors. Environmental risk factors such as pregnancy and birth complications, childhood trauma, migration, social isolation, urbanicity, and substance abuse, alone and in combination, acting at a number of levels over time, influence the individual’s likelihood to develop the disorder. There are no studies on mental health in Yemen in general and schizophrenia in particular. Thus, the aim of this study was to study the non-genetic risk factors of schizophrenia. The specific objectives were to compare exposure to suspected risk factors for schizophrenia in a cohort of schizophrenia patients with those randomly selected from the community. Methods: The researchers approached inpatient in Al-Amal Hospital for Psychiatric Diseases with a diagnosis of schizophrenia. Patients from this list were then randomly selected using the card-shuffling technique. Patients were included in the study if a review of their records confirmed a diagnosis of schizophrenia according to DSM IV criteria, they were ≥18 years old, and had attended the clinics between the period January 2021 and December 2021. Controls were from general population by selected randomly from the list of censuses by simple random selection from Sana’a governorate. Results: Regarding associated risk factors of schizophrenia, there was significant association with low income (OR= 7.1), loss work (OR=57), smoking (OR=5.9) , Khat chewing (OR=12.4), birth complications (OR=7.2) , 1-6 Apgar scores (OR=1.8), older paternal age (OR=3.2), the spring birth (OR=2.2), and winter birth (OR=1.9), childhood trauma (OR=1.9), cannabis (OR=7.4), hypertension(OR=4.7) , and diabetics (OR=6.6). Conclusion: Future research in Yemen should also explore potential protective factors in groups at risk for psychotic disorders. A new area of ​​research should involve big data and predictive models, by replacing traditional paper notes with electronic patient records.

Clinical implications of incorporating genetic and non-genetic risk factors in CanRisk-based breast cancer risk prediction

BackgroundBreast cancer (BC) risk prediction models consider cancer family history (FH) and germline pathogenic variants (PVs) in risk genes. It remains elusive to what extent complementation with polygenic risk score (PRS) and non-genetic risk factor (NGRFs) data affects individual intensified breast surveillance (IBS) recommendations according to European guidelines. MethodsFor 425 cancer-free women with cancer FH (mean age 40·6 years, range 21–74), recruited in France, Germany and the Netherlands, germline PV status, NGRFs, and a 306 variant-based PRS (PRS306) were assessed to calculate estimated lifetime risks (eLTR) and estimated 10-year risks (e10YR) using CanRisk. The proportions of women changing country-specific European risk categories for IBS recommendations, i.e. ≥20 % and ≥30 % eLTR, or ≥5 % e10YR were determined. FindingsOf the women with non-informative PV status, including PRS306 and NGRFs changed clinical recommendations for 31·0 %, (57/184, 20 % eLTR), 15·8 % (29/184, 30 % eLTR) and 22·4 % (41/183, 5 % e10YR), respectively whereas of the women tested negative for a PV observed in their family, clinical recommendations changed for 16·7 % (25/150), 1·3 % (2/150) and 9·5 % (14/147). No change was observed for 82 women with PVs in high-risk genes (BRCA1/2, PALB2). Combined consideration of eLTRs and e10YRs identified BRCA1/2 PV carriers benefitting from IBS <30 years, and women tested non-informative/negative for whom IBS may be postponed. InterpretationFor women who tested non-informative/negative, PRS and NGRFs have a considerable impact on IBS recommendations. Combined consideration of eLTRs and e10YRs allows personalizing IBS starting age. FundingHorizon 2020, German Cancer Aid, Federal Ministry of Education and Research, Köln Fortune.

A Systematic Review and Critical Assessment of Breast Cancer Risk Prediction Tools Incorporating a Polygenic Risk Score for the General Population.

Single nucleotide polymorphisms (SNPs) in the form of a polygenic risk score (PRS) have emerged as a promising factor that could improve the predictive performance of breast cancer (BC) risk prediction tools. This study aims to appraise and critically assess the current evidence on these tools. Studies were identified using Medline, EMBASE and the Cochrane Library up to November 2022 and were included if they described the development and/ or validation of a BC risk prediction model using a PRS for women of the general population and if they reported a measure of predictive performance. We identified 37 articles, of which 29 combined genetic and non-genetic risk factors using seven different risk prediction tools. Most models (55.0%) were developed on populations from European ancestry and performed better than those developed on populations from other ancestry groups. Regardless of the number of SNPs in each PRS, models combining a PRS with genetic and non-genetic risk factors generally had better discriminatory accuracy (AUC from 0.52 to 0.77) than those using a PRS alone (AUC from 0.48 to 0.68). The overall risk of bias was considered low in most studies. BC risk prediction tools combining a PRS with genetic and non-genetic risk factors provided better discriminative accuracy than either used alone. Further studies are needed to cross-compare their clinical utility and readiness for implementation in public health practices.

The genetics and disease mechanisms of rhegmatogenous retinal detachment.

Rhegmatogenous retinal detachment (RRD) is a sight threatening condition that warrants immediate surgical intervention. To date, 29 genes have been associated with monogenic disorders involving RRD. In addition, RRD can occur as a multifactorial disease through a combined effect of multiple genetic variants and non-genetic risk factors. In this review, we provide a comprehensive overview of the spectrum of hereditary disorders involving RRD. We discuss genotype-phenotype correlations of these monogenic disorders, and describe genetic variants associated with RRD through multifactorial inheritance. Furthermore, we evaluate our current understanding of the molecular disease mechanisms of RRD-associated genetic variants on collagen proteins, proteoglycan versican, and the TGF-β pathway. Finally, we review the role of genetics in patient management and prevention of RRD. We provide recommendations for genetic testing and prophylaxis of at-risk patients, and hypothesize on novel therapeutic approaches beyond surgical intervention.

An early prediction model for type 2 diabetes mellitus based on genetic variants and nongenetic risk factors in a Han Chinese cohort.

We aimed to construct a prediction model of type 2 diabetes mellitus (T2DM) in a Han Chinese cohort using a genetic risk score (GRS) and a nongenetic risk score (NGRS). A total of 297 Han Chinese subjects who were free from type 2 diabetes mellitus were selected from the Tianjin Medical University Chronic Disease Cohort for a prospective cohort study. Clinical characteristics were collected at baseline and subsequently tracked for a duration of 9 years. Genome-wide association studies (GWASs) were performed for T2DM-related phenotypes. The GRS was constructed using 13 T2DM-related quantitative trait single nucleotide polymorphisms (SNPs) loci derived from GWASs, and NGRS was calculated from 4 biochemical indicators of independent risk that screened by multifactorial Cox regressions. We found that HOMA-IR, uric acid, and low HDL were independent risk factors for T2DM (HR >1; P<0.05), and the NGRS model was created using these three nongenetic risk factors, with an area under the ROC curve (AUC) of 0.678; high fasting glucose (FPG >5 mmol/L) was a key risk factor for T2DM (HR = 7.174, P< 0.001), and its addition to the NGRS model caused a significant improvement in AUC (from 0.678 to 0.764). By adding 13 SNPs associated with T2DM to the GRS prediction model, the AUC increased to 0.892. The final combined prediction model was created by taking the arithmetic sum of the two models, which had an AUC of 0.908, a sensitivity of 0.845, and a specificity of 0.839. We constructed a comprehensive prediction model for type 2 diabetes out of a Han Chinese cohort. Along with independent risk factors, GRS is a crucial element to predicting the risk of type 2 diabetes mellitus.

Multiple long-term conditions in people with psoriasis: alatent class and bidirectional Mendelian randomization analysis.

Coexisting long-term conditions (LTCs) in psoriasis and their potential causal associations with the disease are not well -established. To determine distinct clusters of LTCs in people with psoriasis and the potential bidirectional causal association between these LTCs and psoriasis. Using latent class analysis, cross-sectional data from people with psoriasis from the UK Biobank were analysed to identify distinct psoriasis-related comorbidity profiles. Linkage disequilibrium score regression (LDSR) was applied to compute the genetic correlation between psoriasis and LTCs. Two-sample bidirectional Mendelian randomization (MR) analysis assessed the potential causal direction using independent genetic variants that reached genome-wide significance (P < 5 × 10-8). Five comorbidity clusters were identified in a population of 10 873 people with psoriasis. LDSR revealed that psoriasis was positively genetically correlated with heart failure [genetic correlation (rg) = 0.23, P = 8.8 × 10-8], depression (rg = 0.12, P = 2.7 × 10-5), coronary artery disease (CAD; rg = 0.15, P = 2 × 10-4) and type 2 diabetes (rg = 0.19, P = 3 × 10-3). Genetic liability to CAD was associated with an increased risk of psoriasis [inverse variance weighted (IVW) odds ratio (ORIVW) 1.159, 95% confidence interval (CI) 1.055-1.274; P = 2 × 10-3]. The MR pleiotropy residual sum and outlier (MR-PRESSO; ORMR-PRESSO 1.13, 95% CI 1.042-1.228; P = 6 × 10-3) and the MR-robust adjusted profile score (RAPS) (ORMR-RAPS 1.149, 95% CI 1.062-1.242; P = 5 × 10-4) approaches corroborate the IVW findings. The weighted median (WM) generated similar and consistent effect estimates but was not statistically significant (ORWM 1.076, 95% CI 0.949-1.221; P = 0.25). Evidence for a suggestive increased risk was detected for CAD (ORIVW 1.031, 95% CI 1.003-1.059; P = 0.03) and heart failure (ORIVW 1.019, 95% CI 1.005-1.033; P = 9 × 10-3) in those with a genetic liability to psoriasis; however, MR sensitivity analyses did not reach statistical significance. Five distinct clusters of psoriasis comorbidities were observed with these findings to offer opportunities for an integrated approach to comorbidity prevention and treatment. Coexisting LTCs share with psoriasis common genetic and nongenetic risk factors, and aggressive lifestyle modification in these people is anticipated to have an impact beyond psoriasis risk. Genetically predicted CAD is possibly associated with an increased risk of psoriasis, altering our prior knowledge.

Inflammatory Conditions During Pregnancy and Risk of Autism and Other Neurodevelopmental Disorders

BackgroundMaternal inflammation can result from immune dysregulation and metabolic perturbations during pregnancy. Whether conditions associated with inflammation during pregnancy increase the likelihood of autism spectrum disorder (ASD) or other neurodevelopmental disorders (DDs) is not well understood. MethodsWe conducted a case-control study among children born in California from 2011 to 2016 to investigate maternal immune-mediated and cardiometabolic conditions during pregnancy and risk of ASD (n = 311) and DDs (n = 1291) compared with children from the general population (n = 967). Data on maternal conditions and covariates were retrieved from electronic health records. Maternal genetic data were used to assess a causal relationship. ResultsUsing multivariable logistic regression, we found that mothers with asthma were more likely to deliver infants later diagnosed with ASD (odds ratio [OR] = 1.62, 95% CI: 1.15–2.29) or DDs (OR = 1.30, 95% CI: 1.02–1.64). Maternal obesity was also associated with child ASD (OR = 1.51, 95% CI: 1.07–2.13). Mothers with both asthma and extreme obesity had the greatest odds of delivering an infant later diagnosed with ASD (OR = 16.9, 95% CI: 5.13–55.71). These increased ASD odds were observed among female children only. Polygenic risk scores for obesity, asthma, and their combination showed no association with ASD risk. Mendelian randomization did not support a causal relationship between maternal conditions and ASD. ConclusionsInflammatory conditions during pregnancy are associated with risk for neurodevelopmental disorders in children. These risks do not seem to be due to shared genetic risk; rather, inflammatory conditions may share nongenetic risk factors with neurodevelopmental disorders. Children whose mothers have both asthma and obesity during pregnancy may benefit from earlier screening and intervention.

A metabolomic perspective on the mechanisms by which environmental pollutants and lifestyle lead to male infertility.

The incidence of male infertility (MI) is rising annually. According to epidemiological studies, environmental pollution (e.g., organic, inorganic, and air pollutants), occupational exposure (e.g., high temperature, organic solvents, and pesticides), and poor lifestyle (e.g., diet, sleep, smoking, alcohol consumption, and exercise) are important non-genetic causative factors of MI. Due to multiple and complex causative factors, the dose-effect relationship, and the uncertainty of pathogenicity, the pathogenesis of MI is far from fully clarified. Recent data show that the pathogenesis of MI can be monitored by the metabolites in serum, seminal plasma, urine, testicular tissue, sperm, and other biological samples. It is considered that these metabolites are closely related to MI phenotypes and can directly reflect the individual pathological and physiological conditions. Therefore, qualitative and quantitative analysis of the metabolome, the related metabolic pathways, and the identification of biomarkers will help to explore the MI-related metabolic problems and provide valuable insights into its pathogenic mechanisms. Here, we summarized new findings in MI metabolomics biomarkers research and their abnormal metabolic pathways triggered by the presented non-genetic risk factors, providing a metabolic landscape of semen and seminal plasma in general MI patients. Then, we compared the similarities and differences in semen and seminal plasma biomarkers between MI patients exposed to environmental and poor lifestyle factors and MI patients in general, and summarized some common biomarkers. We provide a better understanding of the biological underpinnings of MI pathogenesis, which might offer novel diagnostic, prognostic, and precise treatment approaches to MI.

Suicidal Risk in People with Obsessive Compulsive Disorder

Obsessive compulsive disorder or Obsessive Compulsive Disorder (OCD) is a psychiatric disorder characterized by excessive anxiety, persistent thoughts (obsessions), and repetitive behaviors (compulsions). The prevalence of OCD in Europe ranges from 0.1-2.3% annually and more common in adults. The risk of suicide increases ten times more in OCD sufferers compared to the non-OCD sufferers with prevalence the OCD sufferers who has thoughts of suicide is 23.3%. This literature review aims to determine the risk factors for suicide in OCD patients so that prevention can be carried out in individuals who have risk factors. In this literature review we conducted a search on the PubMed, Google Schoolar, and Researchgate database using the search keyword “Obsessive Compulsive Disorder”, “Obsessive Compulsive Symptoms”, “Suicide”, “Self-murder”, and “Risk Factor”. OCD is a disease with genetic and non-genetic risk factors, can manifest clinically as obsessions and compulsions that occur due to failure in responding to yedasantience signals so that the security motivation system (SMS) will be activated longer than normal. The longer SMS activated, the more depressive symptoms can develop, which tends to give rise to suicidal thoughts. In conclusion, risk factors for suicide in OCD that can be identified earlier will not only help the patient's prognosis but also help them choose treatment steps that are appropriate with the severity of the OCD symptoms.