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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
Assortative mating (AM) is defined as the correlation between matting partners with respect to a phenotype. In humans, AM has been described for different types of anthropometric, socioeconomic, and ...behavioral traits including mental disorders. Partner's similarity with respect to a phenotype can be due to couples’ attraction based on that phenotype (direct assortment), based on a secondary phenotype that is highly correlated to it (indirect assortment), or even as a consequence of phenotypic convergence among partners due to the environmental factors that partners share during their cohabitation. Disentangling the nature of the observed AM for a phenotype is essential to understand its genetic consequence. Assortative mating for heritable traits induces a correlation of genetic values among partners, whereas assortment on environmental factors (e.g. social homogamy) shared by partners does not. The correlation of the genetic values of the partners in turn affects the amount of genetic variance of the trait assorted on, which has implications on its heritability.
To disentangle the underlying causes of AM in mental disorders, we use a population-wide analysis of the Danish population (XXX individuals or pairs). We will compare different types of correlation in pair of relations (e.g., spouses, in-laws, co-in-laws, etc.) to distinguish between assortative mating due to shared genetic factors and assortative mating driven by environmental and social factors in nine mental disorders: substance use, schizophrenia, depression, bipolar, ADHD, autism, phobia, anxiety, and anorexia.
We observed different extend of correlation between pairs of relatives which is the key to distinguishing between assortative mating due to shared genetic factors and assortative mating driven by environmental and social factors.
Our findings will provide valuable insights into the mechanisms underlying AM in mental disorders.
This study is the first to evaluate familial aggregation, heritability and inheritance mode of type 2 diabetes (T2D) in Tehran Lipid Glucose Study (TLGS) participants as a representative sample of ...the Iranian population.
From the ongoing family-based TLGS cohort, 13,741 individuals at least 20 years of age (mean ± standard deviation, 39.71±16.56) were assessed. After correcting family structures using genomic information from the Tehran Cardiometabolic Genetic Study, 2,594 constituent pedigrees were constructed. Familial aggregation was assessed based on genealogic index testing, familial intraclass correlation and positive family history. Family-based heritability was checked with 2 linear mixed models, including 2 different random components: the kinship matrix and the genomic relationship matrix. The mode of inheritance of T2D was investigated by complex segregation analysis (CSA).
Familial aggregation of T2D was significant (p<0.05), and family-based heritability showed a high degree of genetic variation in T2D between individuals at 65% (standard error, 0.034). Within first-degree relatives (parent/offspring and siblings), the likelihood of a parental affect was higher than in siblings (odds ratio, 4.11 vs 1.65). Family history of T2D among first-degree relatives was more noteworthy than for second-degree relatives (odds ratio, 3.84 vs 0.59). CSA revealed that the polygenic model is best to illustrate the mode of inheritance of T2D for TLGS participants.
Our findings demonstrate that the heritability of T2D with polygenic mode in the Iranian population is higher than the global average. We also found that T2D is transmitted equally into siblings, with parental affect the leading risk factor. These data suggest that policymakers should change individual-level to family-level prevention.
C’est la première étude qui porte sur l’évaluation de l’agrégation familiale, de l’héritabilité et du mode de transmission héréditaire du diabète de type 2 (DT2) auprès d’un échantillon représentatif de la population iranienne composé des participants à l’étude sur le glucose et les lipides réalisée à Téhéran (TLGS, de l’anglais Tehran Lipid Glucose Study).
Nous avons évalué 13 741 individus d’au moins 20 (moyenne ± écart type, 39,71 ± 16,56) ans qui faisaient partie de la cohorte familiale de l’étude TLGS en cours. Après la correction des structures familiales à l’aide des informations génomiques de la Tehran Cardiometabolic Genetic Study, nous avons construit 2594 pedigrees constitutifs. L’analyse de l’index généalogique, la corrélation familiale intraclasse et les antécédents familiaux positifs nous ont permis d’évaluer l’agrégation familiale. Nous avons vérifié l’héritabilité familiale à l’aide de 2 modèles linéaires à effets mixtes à 2 composantes aléatoires différentes : la matrice de parenté et la matrice de relations génomique. Nous avons examiné le mode de transmission héréditaire du DT2 au moyen de l’analyse de ségrégation complexe (CSA, de l’anglais complex segregation analysis).
L’agrégation familiale du DT2 était significative (p < 0,05), et l’héritabilité familiale montrait un degré élevé de variation génétique du DT2 entre les individus de 65 % (erreur type, 0,034). Chez les proches de premier degré (parent/enfant et fratrie), la probabilité qu’un parent soit atteint était plus élevée que les frères et sœurs le soient (ratio d’incidence approché, 4,11 vs 1,65). Les antécédents familiaux de DT2 chez les proches de premier degré étaient plus notables que chez les proches de deuxième degré (ratio d’incidence approché, 3,84 vs 0,59). La CSA a révélé que le modèle polygénique est préférable pour illustrer le mode de transmission héréditaire du DT2 chez les participants à l’étude TLGS.
Nos résultats démontrent que l’héritabilité du DT2 selon le modèle polygénique dans la population iranienne est plus élevée que la moyenne dans le monde. Nous avons également observé que le DT2 est transmis également aux frères et sœurs, mais que l’atteinte parentale est le principal facteur de risque. Ces données montrent que les décideurs devraient faire passer la prévention sur le plan individuel à la prévention sur le plan familial.
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