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Abstract Background It is unclear to what extent genetics explain the familial clustering and the co-occurrence of distinct cardiometabolic disorders in the general population. We therefore aimed to quantify the familial (co-)aggregation of various cardiometabolic disorders and to estimate the heritability of cardiometabolic traits and their genetic correlations using the large, multi-generational Lifelines Cohort Study. Methods We used baseline data of 162,416 participants from Lifelines. Cardiometabolic disorders including type 2 diabetes (T2D), cardiovascular diseases, hypertension, obesity, hypercholesterolemia, and metabolic syndrome (MetS), were defined in adult participants. Fifteen additional cardiometabolic traits indexing obesity, blood pressure, inflammation, glucose regulation, and lipid levels were measured in all included participants. Recurrence risk ratios (λR) for first-degree relatives (FDR) indexed familial (co-)aggregation of cardiometabolic disorders using modified conditional Cox proportional hazards models and were compared to those of spouses. Heritability (h2), shared environment, and genetic correlation (rg) were estimated using restricted maximum likelihood variance decomposition methods, adjusted for age, age2, and sex. Results Individuals with a first-degree relative with a cardiometabolic disorder had a higher risk of the same disorder, ranging from λFDR of 1.23 (95% CI 1.20–1.25) for hypertension to λFDR of 2.48 (95% CI 2.15–2.86) for T2D. Most of these were higher than in spouses (λSpouses

Abstract Low heart rate variability (HRV) has been widely reported as a predictor for increased mortality. However, the molecular mechanisms are poorly understood. Therefore, this study aimed to identify novel genetic loci associated with HRV and assess the association of phenotypic HRV and genetically predicted HRV with mortality. In a GWAS of 46,075 European ancestry individuals from UK biobank, we identified 17 independent genome-wide significant genetic variants in 16 loci associated with HRV traits. Notably, eight of these loci (RNF220, GNB4, LINCR-002, KLHL3/HNRNPA0, CHRM2, KCNJ5, MED13L, and C160rf72) have not been reported previously. In a prospective phenotypic relationship between HRV and mortality during a median follow-up of seven years, individuals with lower HRV had higher risk of dying from any cause. Genetically predicted HRV, as determined by the genetic risk scores, was not associated with mortality. To the best of our knowledge, the findings provide novel biological insights into the mechanisms underlying HRV. These results also underline the role of the cardiac autonomic nervous system, as indexed by HRV, in predicting mortality.

Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value

Functional disorders represent a prevalent health issue, significantly impacting both individuals and healthcare systems. This multidisciplinary dataset aims to enhance our comprehension of the complex interplay among various factors that contribute to functional somatic syndromes. The dataset comprises data from seemingly healthy adults (aged 18-65) in Isfahan, Iran, who were randomly selected and monitored for four consecutive years. The research data encompasses seven distinct datasets: (a) functional symptom evaluations across multiple body organs, (b) psychological assessments, (c) lifestyle factors, (d) demographic and socioeconomic variables, (e) laboratory measurements, (f) clinical examinations, and (g) historical information. A total of 1930 participants were enrolled at the study's outset in 2017. The first, second, and third annual follow-up rounds were completed with 1697 (2018), 1616 (2019), and 1176 (2020) participants, respectively. This dataset is made available for further analysis by a diverse range of researchers, healthcare policymakers, and clinicians.

Introduction Isfahan functional disorders (ISFUN) cohort study aims to describe the interplay of genetic and environmental factors in shaping the characteristics of functional somatic syndromes (FSS). This study is primarily intended to investigate the epidemiology, risk factors, course and prognosis of FSSs in a sample of adult Iranian population. The other aim is to develop a new delimitation of FSSs based on an integrated multidisciplinary approach comprising of phenotypic and multiomics data.Methods and analysis ISFUN is a population-based prospective cohort study designed to follow a population of randomly selected seemingly healthy adults (18–65 years) through annual visits during a 4-year observation period. Structured questionnaires are used for data collection and clinical assessment of the participants. Questionnaire-based diagnosis of FSSs are validated in a medical interview. Human DNA genotyping, microbial amplicon sequencing and urine analysis is under progress for genomics, microbiota and metabolomics profiling, respectively. Enrolment began in September 2017, and study completion is expected in 2022. A total number of 1943 participants were initially recruited.Ethics and dissemination Ethical approval for data collection was granted by the National Research Ethics Committee of the Iranian Ministry of Health and Medical Education and the Research Ethics Committee of Isfahan University of Medical Sciences (IR.MUI.REC.1395.1.149). Following the description of the study procedure, we obtained written informed consent from all study participants. Study findings will be disseminated through peer-reviewed publications and presentations at scientific meetings.

Physical and mental health are determined by an interplay between nature, for example genetics, and nurture, which encompasses experiences and exposures that can be short or long-lasting. The COVID-19 pandemic represents a unique situation in which whole communities were suddenly and simultaneously exposed to both the virus and the societal changes required to combat the virus. We studied 27,537 population-based biobank participants for whom we have genetic data and extensive longitudinal data collected via 19 questionnaires over 10 months, starting in March 2020. This allowed us to explore the interaction between genetics and the impact of the COVID-19 pandemic on individuals' wellbeing over time. We observe that genetics affected many aspects of wellbeing, but also that its impact on several phenotypes changed over time. Over the course of the pandemic, we observed that the genetic predisposition to life satisfaction had an increasing influence on perceived quality of life. We also estimated heritability and the proportion of variance explained by shared environment using variance components methods based on pedigree information and household composition. The results suggest that people's genetic constitution manifested more prominently over time, potentially due to social isolation driven by strict COVID-19 containment measures. Overall, our findings demonstrate that the relative contribution of genetic variation to complex phenotypes is dynamic rather than static.

Background:Serum calciprotein particle maturation time (T50), a measure of vascular calcification propensity, is associated with cardiovascular morbidity and mortality. We aimed to identify genetic loci associated with serum T50 and study their association with cardiovascular disease and mortality.Methods:We performed a genome-wide association study of serum T50 in 2,739 individuals of European descent participating in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, followed by a two-sample Mendelian randomization (MR) study to examine causal effects of T50 on cardiovascular outcomes. Finally, we examined associations between T50 loci and cardiovascular outcomes in 8,566 community-dwelling participants in the Rotterdam study.Results:We identified three independent genome-wide significant single nucleotide polymorphism (SNPs) in the AHSG gene encoding fetuin-A: rs4917 (p = 1.72 × 10−101), rs2077119 (p = 3.34 × 10−18), and rs9870756 (p = 3.10 × 10−8), together explaining 18.3% of variation in serum T50. MR did not demonstrate a causal effect of T50 on cardiovascular outcomes in the general population. Patient-level analyses revealed that the minor allele of rs9870756, which explained 9.1% of variation in T50, was associated with a primary composite endpoint of all-cause mortality or cardiovascular disease [odds ratio (95% CI) 1.14 (1.01–1.28)] and all-cause mortality alone [1.14 (1.00–1.31)]. The other variants were not associated with clinical outcomes. In patients with type 2 diabetes or chronic kidney disease, the association between rs9870756 and the primary composite endpoint was stronger [OR 1.40 (1.06–1.84), relative excess risk due to interaction 0.54 (0.01–1.08)].Conclusions:We identified three SNPs in the AHSG gene that explained 18.3% of variability in serum T50 levels. Only one SNP was associated with cardiovascular outcomes, particularly in individuals with type 2 diabetes or chronic kidney disease.

Allograft with multiple renal arteries (MRA) is considered to have an increased post-transplantation risk due to vascular and urologic complications. The aim of this study is to inves-tigate the outcome of living donor kidney transplantation using allograft with a single artery and recipients of allografts with multiple arteries. Seven hundred and eighteen consecutive adult kidney transplants done between 1998 and 2007, with living unrelated kidney donors, were enrolled in this retrospective analysis. Data from the group with MRA (n = 60) were compared with those from the group with single renal artery (SRA) (n = 658). Delayed graft function (DGF) was more frequent in recipients′ allografts with more than 2 arteries when compared with SRA recipients (Odds Ratio: 1.2; 95% CI:1.08-1.9, P = 0.02), but there was no difference between SRA and allograft with two arteries. The incidence of acute rejection (AR) was not statistically greater in recipients with MRA. Renal artery stenosis (RAS) occurred more frequently in patients with MRA (8.3% vs. 5.9% and P = 0.02), but other vascular complications such as renal artery thrombosis and hematoma revealed no differences (P > 0.05). Urologic complications such as UVJ obstruction, urinary leakage and ureteropelvic obstruction were not statistically different between the groups. The actuarial 1-year allograft survival rate was comparable in both groups (93.6% vs 96.8%, P = 0.22). Allografts with more than two arteries were associated with increased DGF and RAS, but no surgical or urological complications were detected in our series. Our findings demonstrate that renal allograft transplantation with multiple arteries could be performed with reasonable complications and acceptable outcomes.

Lorestan province in west of Iran, with its rich rivers, established links between the capitals and important cities of Iran during different periods. The need for quick and easy access and permanent communication between these areas with rich rivers and deep valleys, has led to the construction of huge bridges. The undiscovered identity and value of these works for the indigenous people of the region, the country and the international community, destruction of the works and the natural environment associated with it by indigenous people, Absence of the program and the necessary funds for conservation and restoration by trustees, to ignore the natural environment and the natural context of bridges in conservation, all have made these valuable properties destroyed. Accordingly, the purpose of this study was to identify the cultural landscape of the studied bridges and their challenges of conservation in order to provide a basis for a systematic model to conserve them. In this research, information gathering was carried out in the form of library and field studies, and four important bridges were identified on the Kashkan River. Ultimately, the Kashkan Bridge was chosen as a case study due to its location on ancient routs, Sassanian architecture roots and unique architecture. In the following, conservation challenges of cultural landscape of Kashkan historic bridge were identified, analyzed and categorized using qualitative research method, data analysis and its related coding.