The long non‐coding RNAs (lncRNAs) play a critical regulatory role in the host response to the viral infection. However, little is understood about the transcriptome architecture, especially lncRNAs ...pattern during the SARS‐CoV‐2 infection. In the present study, using publicly available RNA sequencing data of bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) samples from COVID‐19 patients and healthy individuals, three interesting findings highlighted: (a) More than half of the interactions between lncRNAs‐PCGs of BALF samples established by three trans‐acting lncRNAs (HOTAIRM1, PVT1 and AL392172.1), which also exhibited the high affinity for binding to the SARS‐CoV‐2 genome, suggesting the major regulatory role of these lncRNAs during the SARS‐CoV‐2 infection. (b) lncRNAs of MALAT1 and NEAT1 are possibly contributed to the inflammation development in the SARS‐CoV‐2 infected cells. (c) In contrast to the 3′ part of the SARS‐CoV‐2 genome, the 5′ part can interact with many human lncRNAs. Therefore, the mRNA‐based vaccines will not show any side effects because of the off‐label interactions with the human lncRNAs. Overall, the putative functionalities of lncRNAs can be promising to design the non‐coding RNA‐based drugs and to inspect the efficiency of vaccines to overcome the current pandemic.
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.
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.
•The FABP2 rs10857064 was significantly associated with increased obesity risk only in the women under the additive model.•The presence of the rs10857064-G allele were not significantly associated ...with obesity in other with genetic models (recessive, dominant, over-dominant, and genotypic) in Iranian population.•The TG haplotype containing rs7670862 and rs10857064 could significantly enhance the risk of obesity in only women, not in men.
FABP2 is one of the key genes involved in obesity development across different populations. However, there is no comprehensive report about the FABP2 contribution to obesity incidence among Iranians. Hence, the present study was designed to assess the probable role of FABP2 polymorphisms in obesity incidence in the Tehran Cardio- metabolic Genetic Study (TCGS) representative Iran population. Unrelated adults who had BMI information for at least 3 consecutive phases of the TCGS cohort were included. The control and case groups were defined as individuals who always had long-term persistent normal weight (20 < BMI < 25; n = 1526) and individuals who were long-term persistent obese (30 < BMI < 35; n = 1313), respectively. The logistic regression test was used to assess the possible association between SNPs located in and around the FABP2 gene with obesity. Also, we used Haploview and SHEsis to perform haplotype analysis to detect whether or not this chromosomal region is correlated with obesity. We found a gender-dependent association between the rs10857064 FABP2 and the risk of obesity. The presence of the rs10857064-G allele could significantly increase the risk of obesity only in women, not men (OR = 1.26; 95 % CI: 1.02–1.57; p = 0.03). Through haplotype analysis, we also detected that the TG haplotype containing rs7670862 and rs10857064 could significantly enhance the risk of obesity in women, further supporting the central role of rs10857064 in women’s long-term obesity risk. In the current study, we revealed that rs10857064-G FABP2 can significantly predispose women to develop obesity. It highlights the importance of different genetic variants in both genders, which could help us to distinguish more efficient obesity screening tests and treatments based on gender in the future.
There is increasing interest of which dietary patterns can modify the association of fat mass and obesity associated (FTO) variants with obesity. This study was aimed at investigating the interaction ...of the Mediterranean dietary pattern (Med Diet) with FTO polymorphisms in relation to obesity phenotypes. Subjects of this nested case-control study were selected from the Tehran Lipid and Glucose Study participants. Each case was individually matched with a normal weight control (
= 1254). Selected polymorphisms (rs1421085, rs1121980, rs17817449, rs8050136, rs9939973, and rs3751812) were genotyped. Genetic risk score (GRS) were calculated using the weighted method. The Mediterranean dietary score (MDS) was computed. Individuals with minor allele carriers of rs9939973, rs8050136, rs1781749, and rs3751812 had lower risk of obesity when they had higher MDS, compared to wild-type homozygote genotype carriers. The obesity risk was decreased across quartiles of MDS in participants with high GRS (OR: 1, 0.8, 0.79, 0.67) compared to individuals with low GRS (OR: 1.33, 1.06, 0.97, 1.12) (Pinteraction < 0.05). No significant interaction between the GRS and MDS on abdominal obesity was found. A higher Med Diet adherence was associated with lower obesity risk in subjects with more genetic predisposition to obesity, compared to those with lower adherence to the Med Diet and lower GRS.
We sought to investigate the familial aggregation and family-based heritability of dietary intakes among adults in a population-based longitudinal study of the Tehran Lipid and Glucose Study (TLSG). ...Total of 4359 males and 5439 females entered our study. We categorized foods into main groups based on the literature on main food groups and their subgroups among the Iranian dietary habits and food culture as follows: grains, fruits, vegetables, dairy, meats, legume, nuts, beverages, snacks, and fats. The intraclass correlation coefficients (ICC) are estimated to verify familial resemblance of dietary habits for all relative pairs and spouses. Family-based heritability is obtained using a mixed effect framework with likelihood-based approach. For almost all food groups, the correlation between parents and offsprings tended to be larger than those of siblings. Family-based heritability of food groups varies from the lowest 6.36% for snacks to the highest 25.67% for fruits, and 25.66% for legume. Our findings indicated weak-to-moderate similarities between parents' and offspring's food intakes; however, the similarity in parent-child food intakes was different, and the correlation in mother-daughter food intakes was stronger than other parent-child correlations, and almost all of dietary components showed strong family-based heritability.
•MC4R risk alleles have not the constant effect on obesity across life periods.•MC4R variants could be considered for obesity screening and treatment in early adulthood.•rs9954571-A has a protective ...role against obesity-related factors.
This population-based longitudinal study is the first investigation that assesses the association of common MC4R SNPs with the obesity-related parameters over time and determines the effect of risk alleles during the three adulthood life periods (early, middle, and late) in a large Iranian cohort, a population with a unique genetic make-up that has been understudied and relatively unexplored. We obtained the genotype of 5370 unrelated adults who participated in the ongoing Tehran Cardiometabolic Genetic Study (TCGS) cohort project for the common MC4R SNPs. Linear regression and linear mixed model analyses were performed to examine the effect of MC4R polymorphisms on maximum BMI and other obesity-related factors over time. We recognized that several SNPs associated with the maximum BMI and the increased BMI, waist circumference, and waist-hip ratio across Iranian adults over a lifetime. Interestingly, we found that rs9954571-A has a yet unreported protective role against obesity-related factors, including BMI, waist circumference, waist-hip ratio, and triglyceride level. Additionally, a survey of the impact of the MC4R risk score throughout the adulthood life periods indicated that the MC4R risk score is influenced both the elevated BMI and waist circumference only during the early adulthood period. Our findings can expand our knowledge about the MC4R genetic variant's contributions to adulthood obesity and highlight the importance of evaluating the genetic components affecting obesity over a lifetime, which could be considered for obesity clinical screening and treatment.
Abstract
Background
We aimed to investigate the familial resemblance of dietary intakes, including energy and nutrients, and the family-based heritability of dietary intake in different age-sex dyads ...of the Tehran cardiometabolic genetic study.
Methods
This cross-sectional study was conducted on 9,798 participants, aged ≥ 18 years, with complete data in each of the third, fourth, fifth, and sixth surveys of the Tehran Cardiometabolic Genetic study, who were eligible to enter the current study based on inclusion and exclusion criteria. Nutrient intake was determined using a valid and reliable food frequency questionnaire (FFQ). FCOR command of the S.A.G.E. software was used to estimate the intra-class correlation coefficients of all relative pairs to verify the family resemblance of dietary nutrient intakes. Classical likelihood-based is used to assess the family-based heritability of dietary nutrient traits.
Results
There were 4338 families with a mean family size of 3.20 ± 2.89, including 1 to 32 members (2567 constituent pedigrees and 1572 singletons) and 3627 sibships. The mean ± SD age of participants was 42.0 ± 15.2 years, and 44.5% were males. The heritability of nutrient intake ranged from 3 to 21%. The resemblance degree of energy intake and most nutrients between spouses or between parents and children is weak to moderate; however, a high resemblance of intake was observed for some food components, especially among spouses, including trans fatty acids (TFAs) (r:0.70), chromium (r:0.44), fiber(r:0.35), pantothenic acid (r:0.31), and vitamin C(r:0.31). Based on our findings, the resemblance of nutrient intake in spouses was greater than in parent-offspring. The similarity in parent–offspring nutrient intake was different, and the correlation in mother-girls nutrient intakes was greater than other parent–child correlations. Also, the lowest resemblance in nutrient intake was observed among siblings.
Conclusions
Our findings suggested a weak-to-moderate similarity between the nutrient intakes of parents and offspring. The resemblance degree in nutrient intake varied between different family pairs; the strongest correlation of nutrients was observed between spouses, which includes TFAs, chromium, fiber, pantothenic acid, and vitamin C. The lowest correlation of nutrients was between siblings, such as carbohydrates, thiamine, niacin, and vitamin K. An individual's nutrient intake can somewhat be influenced by genetics, family relationships, and the effects of parents, although the significant influence of environmental factors should not be ignored.
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.
Missing data is a pervasive problem in longitudinal data analysis. Several single-imputation (SI) and multiple-imputation (MI) approaches have been proposed to address this issue. In this study, for ...the first time, the function of the longitudinal regression tree algorithm as a non-parametric method after imputing missing data using SI and MI was investigated using simulated and real data.
Using different simulation scenarios derived from a real data set, we compared the performance of cross, trajectory mean, interpolation, copy-mean, and MI methods (27 approaches) to impute missing longitudinal data using parametric and non-parametric longitudinal models and the performance of the methods was assessed in real data. The real data included 3,645 participants older than 18 years within six waves obtained from the longitudinal Tehran cardiometabolic genetic study (TCGS). The data modeling was conducted using systolic and diastolic blood pressure (SBP/DBP) as the outcome variables and included predictor variables such as age, gender, and BMI. The efficiency of imputation approaches was compared using mean squared error (MSE), root-mean-squared error (RMSE), median absolute deviation (MAD), deviance, and Akaike information criteria (AIC).
The longitudinal regression tree algorithm outperformed based on the criteria such as MSE, RMSE, and MAD than the linear mixed-effects model (LMM) for analyzing the TCGS and simulated data using the missing at random (MAR) mechanism. Overall, based on fitting the non-parametric model, the performance of the 27 imputation approaches was nearly similar. However, the SI traj-mean method improved performance compared with other imputation approaches.
Both SI and MI approaches performed better using the longitudinal regression tree algorithm compared with the parametric longitudinal models. Based on the results from both the real and simulated data, we recommend that researchers use the traj-mean method for imputing missing values of longitudinal data. Choosing the imputation method with the best performance is widely dependent on the models of interest and the data structure.
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