Population-based Risk of Psychiatric Disorders Associated with Recurrent CNVs.

Recurrent copy number variants (rCNVs) are associated with increased risk of neuropsychiatric disorders but their pathogenic population-level impact is unknown. We provide population-based estimates of rCNV-associated risk of neuropsychiatric disorders for 34 rCNVs in the iPSYCH2015 case-cohort sample (n=120,247). Most observed significant increases in rCNV-associated risk for ADHD, autism or schizophrenia were moderate (HR:1.42-5.00), and risk estimates were highly correlated across these disorders, the most notable exception being high autism-associated risk with Prader-Willi/Angelman Syndrome duplications (HR=20.8). No rCNV was associated with significant increase in depression risk. Also, rCNV-associated risk was positively correlated with locus size and gene constraint. Comparison with published rCNV studies suggests that prevalence of some rCNVs is higher, and risk of psychiatric disorders lower, than previously estimated. In an era where genetics is increasingly being clinically applied, our results highlight the importance of population-based risk estimates for genetics-based predictions.

Genome-wide association study on blood pressure traits in the Iranian population suggests ZBED9 as a new locus for hypertension.

High blood pressure is the heritable risk factor for cardiovascular and kidney diseases. Genome-wide association studies(GWAS) on blood pressure traits increase our understanding of its underlying genetic basis. However, a large proportion of GWAS was conducted in Europeans, and some roadblocks deprive other populations to benefit from their results. Iranians population with a high degree of genomic specificity has not been represented in international databases to date, so to fill the gap, we explored the effects of 652,919 genomic variants on Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Hypertension (HTN) in 7694 Iranian adults aged 18 and over from Tehran Cardiometabolic Genetic Study (TCGS). We identified consistent signals on ZBED9 associated with HTN in the genome-wide borderline threshold after adjusting for different sets of environmental predictors. Moreover, strong signals on ABHD17C and suggestive signals on FBN1 were detected for DBP and SBP, respectively, while these signals were not consistent in different GWA analysis. Our finding on ZBED9 was confirmed for all BP traits by linkage analysis in an independent sample. We found significant associations with similar direction of effects and allele frequency of genetic variants on ZBED9 with DBP (genome-wide threshold) and HTN (nominal threshold) in GWAS summary data of UK Biobank. Although there is no strong evidence to support the function of ZBED9 in blood pressure regulation, it provides new insight into the pleiotropic effects of hypertension and other cardiovascular diseases.

Familial genetic and environmental risk profile and high blood pressure event: a prospective cohort of cardio-metabolic and genetic study.

BACKGROUND AND AIMS: High blood pressure is the heritable risk factor for cardiovascular diseases. We investigated whether the presence of familial genetic and environmental risk factors are associated with increased risk of high blood pressure. METHODS: A total of 4,559 individuals from 401 families were included in this study. Familial aggregation analysis was carried out on systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and waist circumference (WC), and heritability was estimated for SBP and DBP. The association between familial risk factors and blood pressure traits including, incidence of hypertension, SBP and DBP was estimated separately using regression-based two-level Haseman-Elston (HE) method, with individual and familial BMI and WC as environmental exposures and familial genetic profile of known variants as genetic risk factors in 210 index families (≥2 hypertensive cases). Models were adjusted for the two nested sets of covariates. RESULTS: During a follow-up of 15 years, the SBP, DBP, BMI and WC were highly correlated in inter class of mother-offspring and intraclass of sister-sister with heritability of 30 and 25% for DBP and SBP, respectively. Among index families, those whose members with higher familial BMI or WC had significantly increased risk of hypertension and consistent, strong signals of rs2493134 (AGT) linked with SBP and DBP, rs976683 (NLGN1) linked with SBP and HTN, and epistasis of rs2021783 (TNXB) and known genetic variants linked with all blood pressure traits. CONCLUSIONS: Findings from this study show that familial genetic and environmental risk profile increase risk for high blood pressure beyond the effect of the individuals' own risk factors.

Explanation of somatic symptoms by mental health and personality traits: application of Bayesian regularized quantile regression in a large population study.

BACKGROUND: Somatic syndrome is one of the remarkably prevalent issues in primary health care and subspecialty settings. We aimed to elucidate multidimensional associations between somatic symptoms with major mental problems and personality traits in the framework of the quantile regression model with a Bayesian approach. METHODS: A total of 4763 employees at Isfahan University of Medical Sciences and Health Services in Isfahan province, Iran, filled out four validated questionnaires including Hospital Anxiety and Depression Scale (HADS), NEO Questionnaire, General Health Questionnaire (GHQ) and PHQ-15 for somatic symptom severity. In addition, Functional Gastrointestinal Disorders (FGIDs) were determined using Rome IV criteria. Exploratory Factor Analysis (EFA) and Bayesian regularized quantile regression with adaptive LASSO penalization were applied for reduced dimension of somatic symptoms and variable selection and parameter estimation, respectively. RESULTS: The 25 major somatic symptoms were grouped into four factors including general, upper gastrointestinal, lower gastrointestinal and respiratory by EFA. Stress, depression, and anxiety had significant effects on all of the four extracted factors. The effect of anxiety in each four extracted factors was more than stress and depression. Neuroticism and agreeableness had significant effects on all of the four extracted factors, generally (p < 0.05). CONCLUSIONS: Given the high prevalence of somatic symptoms and psychosomatic complaints in correlation with the diverse range of mental co-morbidities, developing more detailed diagnostic tools and methods is crucial; nonetheless, it seems that providing better interdisciplinary approaches in general medical practice is groundwork.