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Abstract Body mass index (BMI) is a well-known risk factor for type 2 diabetes mellitus (T2DM). We aimed to identify BMI trajectory patterns and evaluate their association with T2DM during 18 years of follow-up. We included 6026 participants aged 20 to 65 from the prospective population-based Tehran Lipid and Glucose Study (TLGS). The BMI trajectory patterns were identified using latent growth mixture modeling (LGMM) during the measurement period. The association between the BMI trajectory patterns and future T2DM was evaluated using the Cox proportional hazard regression models. Three BMI trajectory patterns of low-increasing (38.6%), medium-increasing (47.1%), and high-increasing (14.3%) were detected. The participants in the medium-increasing and high-increasing BMI trajectory groups had HRs of 1.87 (95% CI 1.53–2.28) and 3.41(95% CI 2.71–4.29) for T2DM incidence, respectively. Within the normoglycemic subpopulation, the high-increasing BMI group had an HR of 3.82 (95% CI 2.79–5.24) compared to the low-increasing BMI group, while in the prediabetic subpopulation, the high-increasing BMI group had an HR of 2.93 (95% CI 2.04–4.19) compared to the low-increasing BMI group. Body weight varies in a relatively stable pattern in adulthood over the long-term period. Medium and high-increasing BMI trajectory patterns have a significantly increased risk for future T2DM in both normoglycemic and prediabetic individuals. Identifying BMI trajectory patterns can help healthcare providers in early prediction, risk assessment, and monitoring strategies development for the prevention of T2DM.

Abstract This cross-sectional study investigated the associations between urinary sodium (UNa) to potassium (UK) ratio, different phenotypes of elevated blood pressure (BP), and microalbuminuria (MAU) in a cohort of the Tehran Lipid and Glucose Study (TLGS). Adult participants (n = 1782, mean age of 43.0 ± 13.7 years and 46.0% were men) were recruited (2015–2017) for measurements of spot urinary metabolites, i.e., Na, K, creatinine (Cr), microalbumin, and BP. Multinomial logistic regression was used to estimate the relative risk ratios (RRR) of elevated BP phenotypes [i.e., isolated systolic (ISH), diastolic (IDH), and systolic-diastolic (SDH) hypertension], and binary logistic regression was used to estimate odds ratios (ORs) of MAU across quintile categories and per each SD-increment of UNa-K ratio. Mean UNa, UK, and its ratio was 137 ± 57.4, 72.1 ± 36.6 mmol/L, and 2.31 ± 1.41, respectively. Subjects with UNa-K > 3.14 had higher prevalence of ISH (3.4 vs. 1.1%), SDH (11.0 vs. 6.2%), and MAU (14.1 vs. 6.2%) (P for all 3.14 vs.

Abstract This study aimed to examine the association between blood pressure (BP) with health-related quality of life (HRQoL) and emotional states, considering the disease awareness and commitment to treatment among the Iranian adult population. This cross-sectional study uses the data of 7257 and 2449 individuals aged ≥ 20 who had completed data on HRQoL and emotional states, respectively. Linear and logistic regression were used to evaluate the mentioned association. The results showed that commitment to treatment had an inverse association with physical HRQoL in both sexes, except for bodily pain in men. Concerning mental HRQoL, in women, poor medication adherence was linked to a decline in mental HRQoL and social functioning, while good treatment adherence was associated with a reduction in the mental health domain. However, except for a decrease in vitality of hypertensive males with high treatment adherence, no significant association was found between their mental HRQoL and BP. In women, increased commitment to treatment was associated with anxiety, whereas poor commitment was related to depression and stress. The undiagnosed disease was not associated with any HRQoL and emotional state deficits. This study highlights the significance of psychiatric assessment, counseling, and support services while taking into account gender-specific differences among hypertensive patients. It also emphasizes the necessity for customized interventions for both men and women to improve their mental well-being and adherence to treatment.

Abstract Maturity-onset diabetes of the young (MODY) is an uncommon monogenic type of diabetes mellitus. Detecting genetic variants for MODY is a necessity for precise diagnosis and treatment. The majority of MODY genetic predisposition has been documented in European populations and a lack of information is present in Iranians which leads to misdiagnosis as a consequence of defects in unknown variants. In this study, using genetic variant information of 20,002 participants from the family-based TCGS (Tehran Cardiometabolic Genetic Study) cohort, we evaluated the genetic spectrum of MODY in Iran. We concentrated on previously discovered MODY-causing genes. Genetic variants were evaluated for their pathogenicity. We discovered 6 variants that were previously reported in the ClinVar as pathogenic/likely pathogenic (P/LP) for MODY in 45 participants from 24 families (INS in 21 cases, GCK in 13, HNF1B in 8, HNF4A, HNF1A, and CEL in 1 case). One potential MODY variant with Uncertain Risk Allele in ClinVar classification was also identified, which showed complete disease penetrance (100%) in four subjects from one family. This is the first family-based study to define the genetic spectrum and estimate the prevalence of MODY in Iran. The discovered variants need to be investigated by additional studies.

Abstract This study aimed to examine the interaction between diet quality indices (DQIs) and smoking on the incidence of hypertension (HTN), stroke, cardiovascular diseases, and all-cause mortality. We prospectively followed 5720 participants and collected dietary data via a validated food frequency questionnaire to calculate DQI-international (DQI-I) and DQI-revised (DQI-R). Considering an interaction analysis, we classified participants based on diet quality (median: higher/lower) and smoking status. Over 9 years of follow-up, higher diet quality scores were associated with a lower risk of stroke and mortality. While current smokers had a higher risk of stroke and mortality but had a lower risk of developing HTN. Compared to the current smokers with lower diet quality, nonsmokers with higher diet quality according to the DQI-I [HR 0.24; 95% CI (0.08, 0.66)], and DQI-R [HR 0.20; 95% CI (0.07, 0.57)] had a lower risk of stroke. Moreover, the lower risk of mortality was more evident in nonsmokers with higher DQI-I [HR 0.40; 95% CI (0.22–0.75)] and DQI-R scores [HR 0.34; 95% CI (0.18–0.63)] compared to nonsmokers with lower diet quality. While higher DQI-I and DQI-R scores were associated with a lower risk of stroke and mortality, this beneficial effect may be negated by smoking.

Abstract This study investigates the risk of chronic kidney disease (CKD) across four metabolic phenotypes: Metabolically Healthy-No Obesity (MH-NO), Metabolically Unhealthy-No obesity (MU-NO), Metabolically Healthy-Obesity (MH-O), and Metabolically Unhealthy-Obesity (MU-O). Data from the Tehran Lipid and Glucose Study, collected from 1999 to 2020, were used to categorize participants based on a BMI ≥ 30 kg/m2 and metabolic health status, defined by the presence of three or four of the following components: high blood pressure, elevated triglycerides, low high-density lipoprotein, and high fasting blood sugar. CKD, characterized by a glomerular filtration rate

Abstract Dyslipidemia, as a metabolic risk factor, with the strongest and most heritable independent cause of cardiovascular diseases worldwide. We investigated the familial transmission patterns of dyslipidemia through a longitudinal family-based cohort, the Tehran Cardiometabolic Genetic Study (TCGS) in Iran. We enrolled 18,729 individuals (45% were males) aged > 18 years (mean: 38.15 (15.82)) and observed them over five 3-year follow-up periods. We evaluated the serum concentrations of total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol with the first measurement among longitudinal measures and the average measurements (AM) of the five periods. Heritability analysis was conducted using a mixed-effect framework with likelihood-based and Bayesian approaches. The periodic prevalence and heritability of dyslipidemia were estimated to be 65.7 and 42%, respectively. The likelihood of an individual having at least one dyslipidemic parent reveals an OR = 6.94 (CI 5.28–9.30) compared to those who do not have dyslipidemic parents. The most considerable intraclass correlation of family members was for the same-sex siblings, with ICC ~ 25.5%. For serum concentrations, heritability ranged from 33.64 to 60.95%. Taken together, these findings demonstrate that familial transmission of dyslipidemia in the Tehran population is strong, especially within the same-gender siblings. According to previous reports, the heritability of dyslipidemia in this population is considerably higher than the global average.

Abstract We investigated sex-specific associations and their differences between major cardiovascular risk factors and the risk of incident coronary heart disease (CHD) and hard CHD (defined as nonfatal myocardial infarction and CHD death). A total of 7518 (3377 men) participants from the Tehran Lipid and Glucose Study were included. Cox models were used to estimate the hazard ratios (HRs) and women-to-men ratios of HRs for CHD events associated with each risk factor. During 20 years of follow-up (1999–2018), 1068 (631 men) and 345 (238 men) new cases of CHD and hard CHD, respectively, were documented. In total population, the incidence rates per 1000 person-years were 9.5 (9.0–10.1) and 2.9 (2.6–3.2) for CHD and hard CHD, respectively. Hypertension, diabetes, pre-diabetes, and a high waist-to-hip ratio (WHR) were associated with a greater HR of hard CHD in women than men; the women-to-men HRs were 2.85 [1.36–5.98], 1.92 [1.11–3.31], 2.04 [1.09–3.80] and 1.42 [1.10–1.82], respectively. Diabetes was associated with a higher HR of CHD in women than men (ratio of HRs 1.49 (1.10–2.01). In conclusion, we found that hypertension, diabetes, pre-diabetes, and high WHR conferred a greater excess risk of CHD events in women than in men, suggesting that Iranian women may require greater attention for the prevention of CHD events.

Abstract The effectiveness of long-term leisure time physical activity (LTPA) on blood pressure (BP) changes is still under debate. Since adolescence lifestyle behaviors shape the adulthood health profile, this study aimed to investigate the sex-specific impact of LTPA on BP changes from adolescence to young adulthood. This longitudinal study uses the data of 1412 adolescents (52% females) aged 12–18 years through a median follow-up of 12.2 years in the Tehran Lipid and Glucose Study (TLGS) framework. LTPA was calculated using the reliable and valid Iranian version of the modified activity scale (MAQ), and BP was measured at least twice by trained physicians. The linear mixed model was used to examine the study variables, considering individual and intrapersonal differences during the study. The majority of participants consistently demonstrated insufficient LTPA throughout the follow-up assessments, ranging from 54.7 to 67.1% for males and 77.7–83.4% for females. Despite a declining trend in LTPA (β = − 2.77 for males and β = − 1.43 for females), an increasing trend was noticeable in SBP, DBP, and BMI (β = 1.38, β = 1.81, β = 0.97 for males, and β = 0.10, β = 0.20, β = 0.97 for females, respectively). The unadjusted model revealed a significant trend in all variables for both sexes, except for female BP (P = 0.45 for SBP and P = 0.83 for DBP). Using the adjusted model, no significant association was observed between LTPA and changes in BP over time in both sexes. Our study indicates no association between LTPA and BP changes from adolescence to young adulthood. Insufficient LTPA levels, particularly among Iranian females, are likely the primary factor. Further research is crucial to identify appropriate LTPA levels to promote cardiovascular health and implement targeted interventions to achieve optimal LTPA levels in the Iranian population.

Abstract Type 2 diabetes and thyroid function disorders are two common chronic endocrine disorders with the high prevalence in various populations. Metformin is well established as the first-line drug therapy for managing diabetes mellitus. In this meta-analysis, we aimed to determine the effect of metformin on serum TSH and FT4 concentrations in patients with type 2 diabetes. We searched PubMed, Scopus, web of science, Cochrane library, and google scholar to collect information on the effect of metformin on serum TSH and FT4 levels. Demographic and clinical information and serum TSH and FT4 concentrations before and after metformin treatment were extracted. Studies on patients over 18 years of age were included. A total of 11 studies including 1147 patients were selected for the final analysis. In hypothyroid patients, the TSH level decreased significantly after treatment with metformin (Hedges’s g:1.55, 95%CI 0.93–2.16, p-value

Abstract Traditional metabolic syndrome (MetS) criteria have several limitations, which hinder its use in clinical practice. To overcome the limitations, we investigated the association between age- and sex-specific continuous MetS severity score (cMetS-S) and cardiovascular disease (CVD) and mortality beyond MetS components in the framework of the Tehran Lipid and Glucose Study. Participants aged 20–60 years at baseline were included in the study. We excluded participants with CVD, cancer, use of corticosteroids, estimated glomerular filtration rate

Abstract Metabolic syndrome (MetS), defined as the coexistence of interrelated cardiometabolic risk factors, is limited by ignoring the severity of the disease and individuals with a pre-metabolic state. We aimed to develop the first age- and sex-specific continuous MetS severity score in the adult population using confirmatory factor analysis (CFA) based on the MetS components in the Middle East. Using data from the population-based Tehran Lipid and Glucose Study (TLGS) I and II datasets, we conducted CFA of the single factor MetS on 8933 adults (20–60 years old) totally, and in age and sex subgroups. We allowed for different factor loadings across the subgroups to formulate age- and sex-specific continuous MetS severity score equations. Thereafter, we validated these equations in the dataset of TLGS III participants. Triglyceride had the highest factor loading across age and sex subgroups, indicating the most correlation with MetS. Except for women aged 40–60 years, waist circumference was the second most significant factor contributing to MetS. Systolic blood pressure was more closely related to MetS in women than in men. Systolic blood pressure and fasting plasma glucose had the weakest correlation with MetS among the 40–60 age group. Moreover, as women age, the contribution of fasting plasma glucose to MetS tended to decline, while it remained relatively constant in men. The resulting MetS severity score was correlated with age and homeostasis model assessment of insulin resistance. Furthermore, the continuous MetS severity score well predicted the traditional MetS according to receiver operating characteristic analysis in the validation dataset. The age- and sex-specific continuous MetS severity score for the West Asian adult population provides a tangible quantitative measure of MetS enabling clinicians to screen and monitor the individuals at risk and assess their metabolic trends.

Abstract The current study aimed to examine the possible association of the dietary index for insulin resistance (DIR) and the lifestyle index for insulin resistance (LIR), determined by dietary components, body mass index, and physical activity, with the risk of cardiometabolic diseases, including insulin resistance (IR), hypertension (HTN), diabetes, and metabolic syndrome (MetS). This prospective cohort study was performed on 2717 individuals aged ≥ 19 years in the framework of the Tehran Lipid-Glucose Study. Data on nutritional intakes were assessed using a validated food frequency questionnaire. Logistic regression models were used to determine the odds ratio and 95% confidence intervals (ORs and 95% CIs) of cardiometabolic diseases across tertiles of DIR and LIR scores. During 3-years of follow-up, the incidence rate of diabetes, IR, HTN, and MetS was 3%, 13%, 13.9%, and 17%, respectively. In the multi-variables model, after controlling all potential confounders, the risk of IR(OR: 1.65, 95% CI 1.01–2.69, P-trend = 0.047), diabetes (OR: 1.95, 95% CI 1.02–3.74, P-trend = 0.058), and HTN(OR: 1.52, 95% CI 1.07–2.15, P-trend = 0.016) was increased across tertiles of DIR score. Also, the risk of IR (OR: 2.85, 95% CI 1.72–4.73, P-trend

Abstract Due to the central role in insulin secretion, the potassium inwardly-rectifying channel subfamily J member 11 (KCNJ11) gene is one of the essential genes for type 2 diabetes (T2D) predisposition. However, the relevance of this gene to T2D development is not consistent among diverse populations. In the current study, we aim to capture the possible association of common KCNJ11 variants across Iranian adults, followed by a meta-analysis. We found that the tested variants of KCNJ11 have not contributed to T2D incidence in Iranian adults, consistent with similar insulin secretion levels among individuals with different genotypes. The integration of our results with 72 eligible published case–control studies (41,372 cases and 47,570 controls) as a meta-analysis demonstrated rs5219 and rs5215 are significantly associated with the increased T2D susceptibility under different genetic models. Nevertheless, the stratified analysis according to ethnicity showed rs5219 is involved in the T2D risk among disparate populations, including American, East Asian, European, and Greater Middle Eastern, but not South Asian. Additionally, the meta-regression analysis demonstrated that the sample size of both case and control groups was significantly associated with the magnitude of pooled genetic effect size. The present study can expand our knowledge about the KCNJ11 common variant's contributions to T2D incidence, which is valuable for designing SNP-based panels for potential clinical applications in precision medicine. It also highlights the importance of similar sample sizes for avoiding high heterogeneity and conducting a more precise meta-analysis.

Abstract Previous epidemiologic studies debated the association of body mass index (BMI) trends with cardiovascular disease and mortality. This study aimed to evaluate the association of BMI variability and slope with the incidence of Type 2 diabetes mellitus (T2DM) in a sex-stratified 15.8-year follow-up in the population-based Tehran Lipid and Glucose Study (TLGS). Of 10,911 individuals aged 20–60 years, 4981 subjects were included and followed for 15.8-years. The slope coefficient of BMI in the linear regression model represented individuals’ BMI trends up to the incidence of DM. The root mean squared error (RMSE) of the BMI linear trend was selected to reflect BMI variability through six follow-ups. Cox proportional hazards regression was used to investigate the association of the baseline BMI, BMI slope and RMSE with the incidence of T2DM among men and women. Multivariable-adjusted HRs of T2DM for each SD increment in BMI slope was 1.18 (95% CI: 0.94–1.48, p = 0.161) in normal weight men and 1.26 (95% CI: 1.10–1.44, p = 0.001) in overweight and obese men. However, in women, each SD increment in BMI slope increased the risk of T2DM with a HR of 1.19 (95% CI: 1.01–1.40, p = 0.039) in normal weight, and 1.14 (95% CI: 1.08–1.19, p

Abstract Ideal cardiovascular health (CVH) is associated with a lower risk of developing cardiovascular diseases. This study aims to investigate the association of CVH metrics with carotid intima-media thickness (cIMT) as a marker of subclinical atherosclerosis in young adults. A cross-sectional study was performed on 1295 adults, average age of 29.7 ± 4.0 years, selected from the participants of the Tehran Lipid and Glucose Study. The participants were divided into three groups based on the overall CVH score: ideal, intermediate, and poor CVH. Multivariate-adjusted linear regression was used to determine the association of the CVH score with cIMT. Multivariate-adjusted odds ratios (ORs) were calculated for high cIMT (≥ 95% percentile). Also, the independent effects of each ideal CVH metric on cIMT were analyzed. The prevalence of ideal CVH was 6.4% in men and 12.4% in women, and mean cIMT was obtained 0.53 ± 0.09 mm in men and 0.57 ± 0.08 mm in women. A 1-point increase of the CVH score in men and women was associated with a cIMT decrease of 0.009 and 0.011 mm (men: Beta [SE] = − 0.009 [0.003]; women: − 0.011 [0.007], p

Abstract Cardiovascular disease (CVD), as the leading cause of death worldwide, is the collective term named for disorders afflicting the blood vessels and heart. Inflammation and enhanced oxidative stress have been shown as fundamental risk factors in the onset and progression of CVD. Chronic inflammatory conditions attenuate blood levels of antioxidants because of the continuous generation of elevated levels of reactive oxygen species (ROS). A sufficient intake of antioxidants is also suggested to beneficially interfere with CVD by quenching ROS. Antioxidant vitamins and minerals, such as vitamins A, E, and C, and zinc may slow the development and progression of CVD. This study aimed at investigating the association between daily consumption of dietary vitamins A, E, and C, and zinc and the incidence of CVD. Eligible adults (n = 5102) aged ≥ 30 years, were selected from the participants of the Tehran lipid and glucose study with an average follow-up of 5.3 years. Dietary intake was assessed using a valid and reliable semi-quantitative food frequency questionnaire. Anthropometrics and biochemical variables were evaluated at baseline and follow-up examinations. Multivariable Cox proportional hazard regression models were used to estimate the development of CVD associated with total intakes of vitamins A, E, and C, and zinc. This study was conducted on 2253 men and 2849 women aged 47.0 ± 11.6 and 45.6 ± 10.5 years, respectively. The main sources of dietary vitamins A, E, and C and zinc were fruits, vegetables, and legumes. Risk of CVD decreased from quartile 1 to quartile 4 for vitamin E intake (HR 1.00, 0.91, 0.77, and 0.57; P trend = 0.03). The association between the risk of CVD and quartiles of vitamins A, and C and zinc intake was not statistically significant. Our study suggests an inverse association between vitamin E intake and the risk of CVD, emphasizing the potential protective role of fruit and vegetable in the prevention of CVD.

Abstract Sudden cardiac death (SCD) is described as death within one hour, if observed, from the onset of symptoms, and within 24 h of being alive and well if not observe. Study population includes 3705 men and 4446 women, aged ≥ 30 years. Multivariable Cox proportional hazard models were used to determine the risk factors associated with SCD. After a median follow-up of 17.9 years, 244 SCD (165 in males) occurred. The age-standardized incidence rate (95% confidence intervals (CI)) of SCD was 2.3 (2.1–2.7) per 1000 person-year. Current smoking [Hazard ratio (HR): 2.43, 95% CI: 1.73–3.42], high waist circumference [1.49: 1.04–2.12], hypertension [1.39: 1.05–1.84], type 2 diabetes mellitus [2.78: 2.09–3.69], pulse rate ≥ 90 beats per/minute [1.72: 1.22–2.42] and prevalent cardiovascular disease [1.75: 1.26–2.45] were significant risk factors. The corresponding population attributed fractions (PAF) were 14.30, 16.58, 14.03, 19.60, 7.62, and 8.30, respectively. Being overweight [0.58: 0.40–0.83] and obese [0.61: 0.38–0.98] decreased the risk of SCD. After excluding known diabetes cases from our data analysis, the newly diagnosed diabetes still showed an HR of 2.0 (1.32–3.00) with a PAF of 7.15% in the full adjustment model. To deal with sudden death as a catastrophic outcome, multi-component strategies by policy health makers are suggested.

Abstract Considering the dynamic nature of body mass index (BMI) and its importance in determining cardiovascular risks, this study aimed to investigate the life-course trajectory pattern of women’s BMI and its association with cardiovascular risk factors. A total of 1356 couples with 2976 children were recruited and followed up for an average period of 20 years. Latent growth curve modeling was applied to determine women's BMI trajectories; logistic regression was used to investigate the associations between trajectory patterns and cardiovascular risk factors, including hypertension (HTN), dyslipidemia, diabetes mellitus (DM), and obesity. Women were classified into three trajectories, including normal, stage 1 obesity, and stage 2 obesity. Compared to women’s in the normal trajectory group, those in obesity trajectories had higher odds ratios for HTN, DM, and dyslipidemia. Men with obese spouses showed a higher rate of HTN 1.54 (95% CI 1.05–2.25) and DM 1.55; (95% CI 1.00–2.44). The odds of men’s obesity were higher in obese spouses (OR 1.70; 95% CI 1.10–2.62). Offspring of stage 2 obese (OR 2.39; 95% CI 1.67–3.44) and stage 1 obese (OR 4.81; 95% CI 3.16–7.34) mothers were more likely to be obese. Our findings emphasized paying more attention to women with excessive weight to promote familial cardiovascular health in the communities.

Abstract 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.

Abstract Metabolic syndrome (MetS) is one of the most important risk factors for cardiovascular disease. The 11p23.3 chromosomal region plays a potential role in the pathogenesis of MetS. The present study aimed to assess the association between 18 single nucleotide polymorphisms (SNPs) located at the BUD13, ZPR1, and APOA5 genes with MetS in the Tehran Cardio-metabolic Genetics Study (TCGS). In 5421 MetS affected and non-affected participants, we analyzed the data using two models. The first model (MetS model) examined SNPs' association with MetS. The second model (HTg-MetS Model) examined the association of SNPs with MetS affection participants who had a high plasma triglyceride (TG). The four-gamete rules were used to make SNP sets from correlated nearby SNPs. The kernel machine regression models and single SNP regression evaluated the association between SNP sets and MetS. The kernel machine results showed two sets over three sets of correlated SNPs have a significant joint effect on both models (p

Abstract In recent decades, ongoing GWAS findings discovered novel therapeutic modifications such as whole-genome risk prediction in particular. Here, we proposed a method based on integrating the traditional genomic best linear unbiased prediction (gBLUP) approach with GWAS information to boost genetic prediction accuracy and gene-based heritability estimation. This study was conducted in the framework of the Tehran Cardio-metabolic Genetic study (TCGS) containing 14,827 individuals and 649,932 SNP markers. Five SNP subsets were selected based on GWAS results: top 1%, 5%, 10%, 50% significant SNPs, and reported associated SNPs in previous studies. Furthermore, we randomly selected subsets as large as every five subsets. Prediction accuracy has been investigated on lipid profile traits with a tenfold and 10-repeat cross-validation algorithm by the gBLUP method. Our results revealed that genetic prediction based on selected subsets of SNPs obtained from the dataset outperformed the subsets from previously reported SNPs. Selected SNPs’ subsets acquired a more precise prediction than whole SNPs and much higher than randomly selected SNPs. Also, common SNPs with the most captured prediction accuracy in the selected sets caught the highest gene-based heritability. However, it is better to be mindful of the fact that a small number of SNPs obtained from GWAS results could capture a highly notable proportion of variance and prediction accuracy.

Abstract Obesity is the most crucial phenotype in metabolic syndrome (MetS), and waist circumference (WC) and body mass index (BMI) are two common indexes to define obesity. It is an accepted fact that genetic and environmental interaction influence obesity and MetS. Microsatellites are a subcategory of tandem repeats with a length of 1 to 10 nucleotides. Tandem repeats make up repetitive genomic regions. Differences in the number of tandem repeats or their variation (alleles) result in microsatellite polymorphisms. Thus, we attempted to find microsatellite variation associated with WC and BMI in a family-based study. Twelve microsatellite markers were selected to investigate possible genes or chromosomal regions in 91 families with at least one affected MetS. The cut-off values for BMI and WC were considered 25 kg/m2 and 90 cm, respectively. In all members of the families, the strongest association was observed between the marker D11S1304 (allele 1) with both WC and BMI, independently, by the biallelic model in the family-based association test analysis (P

Abstract The genetic variations among individuals are one of the notable factors determining disease severity and drug response. Nowadays, COVID-19 pandemic has been adversely affecting many aspects of human life. We used the Tehran Cardio-Metabolic Genetic Study (TCGS) data that is an ongoing genetic study including the whole-genome sequencing of 1200 individuals and chip genotyping of more than 15,000 participants. Here, the effect of ACE2 variations by focusing on the receptor-binding site of SARS-CoV-2 and ACE2 cleavage by TMPRSS2 protease were investigated through simulations study. After analyzing TCGS data, 570 genetic variations on the ACE2 gene, including single nucleotide polymorphisms (SNP) and insertion/deletion (INDEL) were detected. Interestingly, two observed missense variants, K26R and S331F, which only the first one was previously reported, can reduce the receptor affinity for the viral Spike protein. Moreover, our bioinformatics simulation of 3D structures and docking of proteins explains important details of ACE2-Spike and ACE2-TMPRSS2 interactions, especially the critical role of Arg652 of ACE2 for protease function of TMPRSS2 was uncovered. As our results show that the genetic variation of ACE2 can at least influence the affinity of this receptor to its partners, we need to consider the genetic variations on ACE2 as well as other genes in the pathways that contribute to the pathogenesis of COVID-19 for designing efficient drugs and vaccines.

Abstract To examine the trends of 7 cardiovascular health metrics (CVH metrics) incorporate of smoking, physical activity, diet, body mass index (BMI), fasting plasma glucose (FPG), total cholesterol (TC), and blood pressure (BP) level during three cross-sectional STEPwise approaches to surveillance (STEPS), 2007–2016, among Iranian adults. The study population consisted of 19,841 women and 17,243 men, aged 20–65 years. The CVH metrics were categorized as ‘ideal’, ‘intermediate’, and ‘poor’. The sex-stratified weighted prevalence rate of each CVH metrics was reported. The conditional probability of each poor versus combined intermediate and ideal metric was analyzed using logistic regression. In 2016 compared to 2007, the prevalence of poor BP level (20.4% vs. 23.7%), smoking (13.7% vs. 23.8%), TC ≥ 240 mg/dl (2.4% vs. 11.2%) and FPG

Abstract It is well documented that physical inactivity is related to weight gain and a whole host of chronic diseases. This study investigated trends of low physical activity among Iranian adolescents in urban and rural areas between 2006–2011. A total of 12,178 adolescents, aged between 15 and 19 years, participated in National Surveys of Risk Factors for Non-Communicable Diseases. Data on physical activity was obtained using the global physical activity questionnaire. A complex sample survey and multinomial logistic regression were used to model physical activity levels. The percentage of adolescents who had low levels of physical activity increased from 2006 to 2011 in both urban and rural areas. Low and moderate levels of physical activity were lower in rural girls as compared with urban girls, with a prevalence ratio of 0.59 (95% CI 0.47–0.74) and 0.59 (95% CI 0.47–0.74), respectively. The corresponding values for boys residing in rural areas compared with boys in urban areas were 0.56 (95% CI 0.43–0.75) and 0.60 (95% CI 0.48–0.74), respectively. The adolescents' lifestyles showed an increasing trend for physical inactivity in both genders; however, in rural areas, only girls had a rising affinity for a sedentary lifestyle throughout the 2006–2011 years.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Abstract We identified risk patterns associated with incident coronary heart disease (CHD) using survival tree, and compared performance of survival tree versus Cox proportional hazards (Cox PH) in a cohort of Iranian adults. Data on 8,279 participants (3,741 men) aged ≥30 yr were used to analysis. Survival trees identified seven subgroups with different risk patterns using four [(age, non-HDL-C, fasting plasma glucose (FPG) and family history of diabetes] and five [(age, systolic blood pressure (SBP), non-HDL-C, FPG and family history of CVD] predictors in women and men, respectively. Additional risk factors were identified by Cox models which included: family history of CVD and waist circumference (in both genders); hip circumference, former smoking and using aspirin among men; diastolic blood pressure and lipid lowering drug among women. Survival trees and multivariate Cox models yielded comparable performance, as measured by integrated Brier score (IBS) and Harrell’s C-index on validation datasets; however, survival trees produced more parsimonious models with a minimum number of well recognized risk factors of CHD incidence, and identified important interactions between these factors which have important implications for intervention programs and improve clinical decision making.

Abstract There are conflicting data on the impact of zinc transporter 8 (ZNT8) gene variations on the metabolic syndrome (MetS). Hence, the effects of the interaction between rs13266634 and dietary factors on the risk of MetS were investigated in this study. Subjects of this nested case-control study were selected from the participants in Tehran Lipid and Glucose Study. Each of the cases (n = 817) was individually matched with a control. Dietary patterns were determined using factor analysis. The ZNT8 rs13266634 were genotyped by the Tetra-refractory mutation system-polymerase chain reaction analysis. Two dietary patterns were extracted. There were no significant interactions between the ZNT8 SNP and the dietary patterns on the risk of MetS or its components. An interaction was observed between rs13266634 and the omega-3 fatty acid intakes on the risk of MetS in subjects with the CC genotype (P interaction