Using the Bayesian variational spike and slab model in a genome-wide association study for finding associated loci with bipolar disorder.

OBJECTIVE: The genome-wide association studies (GWAS) analysis, the most successful technique for discovering disease-related genetic variation, has some statistical concerns, including multiple testing, the correlation among variants (single-nucleotide polymorphisms) based on linkage disequilibrium and omitting the important variants when fitting the model with just one variant. To eliminate these problems in a small sample-size study, we used a sparse Bayesian learning model for finding bipolar disorder (BD) genetic variants. METHODS: This study used the Wellcome Trust Case Control Consortium data set, including 1998 BD cases and 1500 control samples, and after quality control, 380,628 variants were analysed. In this GWAS, a Bayesian logistic model with hierarchical shrinkage spike and slab priors was used, with all variants considered simultaneously in one model. In order to decrease the computational burden, an alternative inferential method, Bayesian variational inference, has been used. RESULTS: Thirteen variants were selected as associated with BD. The three of them (rs7572953, rs1378850 and rs4148944) were reported in previous GWAS. Eight of which were related to hemogram parameters, such as lymphocyte percentage, plateletcrit and haemoglobin concentration. Among selected related genes, GABPA, ELF3 and JAM2 were enriched in the platelet-derived growth factor pathway. These three genes, along with APP, ARL8A, CDH23 and GPR37L1, could be differential diagnostic variants for BD. CONCLUSIONS: By reducing the statistical restrictions of GWAS analysis, the application of the Bayesian variational spike and slab models can offer insight into the genetic link with BD even with a small sample size. To uncover related variations with other traits, this model needs to be further examined.

Under-reported time-varying MINAR(1) process for modeling multivariate count series.

A time-varying multivariate integer-valued autoregressive of order one (tvMINAR(1)) model is introduced for the non-stationary time series of correlated counts when under-reporting is likely present. A non-diagonal autoregression probability network is structured to preserve the cross-correlation of multivariate series, provide a necessary condition to ease model-fittings computations, and derive the full likelihood using the Viterbi algorithm. The motivating construction applies to fully under-reported counts that rely on a mixture presentation of the random thinning operator. Simulation studies are conducted to examine the proposed model, and the analysis of COVID-19 daily cases is accomplished to highlight its usefulness in applications. Finally, the comparison of models is presented using the posterior predictive checking method.

Prevalence and predictors of prediabetes and its coexistence with high blood pressure in first-degree relatives of patients with type 2 diabetes: A 9-year cohort study.

BACKGROUND: Prediabetes is strongly associated with high blood pressure; however, a little is known about prediabetes and high blood pressure comorbidity in the high-risk individuals. This is the first study in the world to assess the long-term effects of risk factors associated with high blood pressure and prediabetes comorbidity in the first-degree relatives (FDRs) of type 2 diabetes mellitus (T2DM) patients. MATERIALS AND METHODS: The longitudinal data obtained from 1388 nondiabetic FDRs of T2DM patients with at least two visits between 2003 and 2011. We used univariate and bivariate mixed-effects logistic regressions with a Bayesian approach to identify longitudinal predictors of high blood pressure and prediabetes separately and simultaneously. RESULTS: The baseline prevalence of high blood pressure, prediabetes, and the coexistence of both was 27.4%, 19.1%, and 29.8%, respectively. The risks of high blood pressure and prediabetes were increased by one-unit raise in the age (odds ratio [OR] of high blood pressure: 1.419 (95% credible intervals [CI], 1.077-1.877), prediabetes: 1.055 (95% CI: 1.040-1.068)) and one-unit raise in remnant-cholesterol (OR of high blood pressure: 1.093 (95%CI, 1.067-1.121), and prediabetes: 1.086 (95% CI, 1.043-1.119)). Obese participants were more likely to have high blood pressure (OR: 2.443 [95% CI, 1.978-3.031]) and prediabetes (OR: 1.399 [95% CI, 1.129-1.730]) than other participants. CONCLUSION: We have introduced remnant-cholesterol, along with obesity and age, as a significant predictor of prediabetes, high blood pressure, and the coexistence of both in the FDRs of diabetic patients. Obesity index and remnant-cholesterol showed the stronger effects on high blood pressure and prediabetes comorbidity than on each condition separately.

Evaluating the effect of Coriandrum sativum syrup on being migraine-free using mixture models.

Background: Coriandrum sativum (coriander) is prescribed as a treatment for headache in traditional Persian medicine. Several investigations have been carried out to find the medicinal properties of this plant. However, no study has evaluated the effectiveness of this plant on becoming migraine-free. Methods: Sixty-eight migraineurs were randomly allocated to two equal groups of intervention and control . Each received 500 mg of sodium valproate in addition to 15 mL of coriander or placebo syrup three times a day. We followed subjects and recorded their migraine duration in the 1st, 2nd, 3rd, and 4th weeks. We applied an appropriate statistical model so as to consider special features of the data, which led to more accurate results using SAS 9.4 Results: Our findings showed that the probability of being migraine-free was not only considerably higher in final weeks of the study (p<0.001) in all patients of the intervention group than placebo group, but it was also significantly higher in patients less than 30 years of age compared to patients older than 30 years old. Migraine duration in migraineurs using coriander syrup reduced considerably during the study (p<0.001). Conclusion: The finding of this study revealed that coriander has a significant effect both on the probability of being migraine free and the duration of migraine attacks. Its effects were more significant during the final weeks of study.

Effects of time-invariant covariates on the estimation of longitudinal trends for transition mixed models.

In this paper, we investigate the impact of time-invariant covariates when fitting transition mixed models. This is carried out by emphasizing on the role of baseline responses on the estimation process. Transition models are allowed for two cases of exogenous and endogenous baseline responses. We illustrate these concepts in the special case of transition linear mixed models with centered time-varying covariates. Results of our simulation studies show that the omission, or the inclusion, of time-invariant covariates is not important in models with exogenous baseline responses, while it has an essential effect on fitting models with the endogenous baseline responses. It is also emphasized that the effect becomes minor when the endogeneity issue is handled. The practical consequences are illustrated in the analysis of a real data set taken from medical sciences.

Pediatric metabolic syndrome and cell blood counts: bivariate Bayesian modeling.

Cell blood counts are components of hematological parameters and indicators of pro-inflammatory states. They are proposed to be associated with metabolic syndrome (MetS). This study aimed to assess the relationship of the white blood cell (WBC) and the red blood cell (RBC) counts with components of MetS in the pediatric age group. The sample consisted of 300 children (152 boys) aged 6-12 years. Hierarchical Bayesian analysis of the bivariate Poisson regression model was used to estimate the effect of various components of MetS according to the cell blood counts. We found that RBC and WBC counts were correlated with the fasting blood glucose, the waist-to-height ratio, serum triglycerides and the blood pressure levels adjusted for age, the body mass index, gender, total cholesterol, low-density lipoprotein cholesterol and the hip circumference. The high-density lipoprotein cholesterol was correlated with the RBC counts based on 95% high posterior density regions for parameters in the Bayesian model. Our findings may serve as confirmatory evidence for the beginning of inflammatory process related to the cardio-metabolic factors from early life.

Bayesian analysis of multivariate mixed models for a prospective cohort study using skew-elliptical distributions.

Classical multivariate mixed models that acknowledge the correlation of patients through the incorporation of normal error terms are widely used in cohort studies. Violation of the normality assumption can make the statistical inference vague. In this paper, we propose a Bayesian parametric approach by relaxing this assumption and substituting some flexible distributions in fitting multivariate mixed models. This strategy allows for the skewness and the heavy tails of error-term distributions and thus makes inferences robust to the violation. This approach uses flexible skew-elliptical distributions, including skewed, fat, or thin-tailed distributions, and imposes the normal model as a special case. We use real data obtained from a prospective cohort study on the low back pain to illustrate the usefulness of our proposed approach.

Multistate Models to Predict Development of Late Complications of Type 2 Diabetes in an Open Cohort Study.

BACKGROUND: Increase in the prevalence of type 2 diabetic mellitus (T2DM) as a complex disease, its complications, and spread has become a dominant global health threat in recent decades. OBJECTIVE: The aim of the current study was to investigate the impact of risk factors and transition probability on the development and progression of the late complications of T2DM. METHODS: This study was an open cohort one which was conducted at Isfahan Endocrine and Metabolism Research Center (IEMRC). The data were collected from 1993 to 2018. The sample size consisted of 2519 adults diagnosed with type 2 diabetes. We applied the homogeneous multistate models including no complication, retinopathy alone, coronary artery disease (CAD), microalbuminuria, retinopathy and CAD, and the final absorbing mortality states. RESULTS: Based on our results, time-varying hypertension strongly intensified the hazard of transition to mortality in CAD, no complication, CAD and retinopathy, and retinopathy patients by 4.99, 4.09, 3.42, and 2.65 times, respectively. Hypertension seemed to be a potential factor for the transition of microalbuminuria to no complication in diabetic patients. One-unit increase in LDL increased the hazard ratio of transition from CAD, and retinopathy and CAD to mortality by 1.8% and 2.4%, respectively. Moreover, one level increase in time-varying HbA1c increased the hazard ratio of transition to retinopathy and mortality among no complication diabetic patients by 30% and 67%, respectively. One level increase in time-varying HbA1c also intensified the hazard ratio of transition from retinopathy to mortality by 45%. The same level of increase in time-varying HbA1c also intensified the hazard ratio of transition from CAD alone to CAD and retinopathy, and microalbuminuria to retinopathy by 26% and 50%, respectively. CONCLUSION: In addition to glycemic control, our study indicates that controlling hypertension and hyperlipidemia is more effective in reducing mortality and the diabetic macro- and microvascular complications.

Long-term nuts intake and metabolic syndrome: A 13-year longitudinal population-based study.

BACKGROUND & AIMS: The ability of nuts to improve the conditions of the metabolic syndrome (MetS) is now well established. However, few longitudinal studies examined the impact of nuts on MetS and those that have been ongoing considered baseline measurement of nuts intake. The associations between nuts intake and the risk of MetS was longitudinally assessed in our study using repeated measurements of nuts intake. METHODS: The population-based longitudinal study was conducted on a sub-sample of the Isfahan Cohort Study (ICS), including 1387 adults, aged ≥ 35 years. A validated food frequency questionnaire was applied to obtain data on the nuts intake. International Diabetes Federation (IDF) criteria were used to define MetS. The longitudinal relation between the trend of nuts intake and the risk and severity of MetS was examined using the Logistic and Cumulative Logit regressions with considering mixed random effects. RESULTS: After adjustment for potential confounders, a statistically significant inverse association was found in severity of MetS (the number of positive criteria) in the second quartile of nuts compared with the lowest quartile (OR: 0.77, 95% PI: 0.63-0.96; P trend: 0.03). Nuts intake was inversely associated with MetS risk among participants in the second quartile compared with the lowest quartile (OR: 0.76, 95% PI: 0.59-0.96; P trend: 0.14). CONCLUSIONS: Nuts intake demonstrated a significant, inverse association with the risk and severity of MetS after a 13-year follow-up period in a cohort of the Iranian population.

Cross-sectional and longitudinal assessments of risk factors associated with hypertension and moderately increased albuminuria comorbidity in patients with type 2 diabetes: a 9-year open cohort study.

BACKGROUND: Moderately increased albuminuria (MIA) is strongly associated with hypertension (HTN) in patients with type 2 diabetic mellitus (T2DM). However, the association between risk factors and coexisting HTN and MIA remains unassessed. OBJECTIVES: This study aimed to determine both cross-sectional and longitudinal associations of risk factors with HTN and MIA comorbidity in patients with T2DM. METHODS: A total of 1,600 patients with T2DM were examined at baseline and longitudinal data were obtained from 1,337 T2DM patients with at least 2 follow-up visits to assess the presence of HTN alone (yes/no), MIA alone (yes/no) and the coexistence of both (yes/no) in a 9-year open cohort study between 2004 and 2013. Bivariate mixed-effects logistic regression with a Bayesian approach was employed to evaluate associations of risk factors with HTN and MIA comorbidity in the longitudinal assessment. RESULTS: After adjustment for age and BMI, patients with uncontrolled plasma glucose, as a combined index of the glucose profile, were more likely to have HTN [odds ratio (OR): 1.73 with 95% Bayesian credible intervals (BCI) 1.29-2.20] and MIA [OR: 1.34 ( 95% BCI 1.13-1.62)]. The risks of having HTN and MIA were increased by a one-year raise in diabetes duration [with 0.89 (95% BCI 0.84-0.96) and 0.81 (95% BCI 0.73-0.92) ORs, respectively] and a one-unit increase in non-high-density lipoprotein-cholesterol (Non-HDL-C) [with 1.30 (95% BCI 1.23-1.34) and 1.24 (95% BCI 1.14-1.33) ORs, respectively]. CONCLUSIONS: T2DM patients with HTN, MIA, and the coexistence of both had uncontrolled plasma glucose, significantly higher Non-HDL-C, and shorter diabetes duration than the other T2DM patients. Duration of diabetes and uncontrolled plasma glucose index showed the stronger effects on HTN and MIA comorbidity than on each condition separately.

A placebo-controlled clinical trial to evaluate the effectiveness of massaging on infantile colic using a random-effects joint model.

BACKGROUND: Infantile colic viewed as a non-dangerous prevalent issue could lead to stress in parents and long-term negative consequences in ex-colicky children. Researchers have not been successful in finding a certain treatment for colic symptoms. Studies suggest completely different approaches as its treatment. Massage therapy as an alternative method in reducing colic symptoms has been recommended in several studies. METHODS: A total of 100 colicky infants in a single blind study were randomly specified to two equal groups of intervention and control. Infants in the intervention group received massage for 15-20 minutes once during the day and once at night before sleep, while infants in the control group were rocked for 15-25 minutes when the symptoms of colic appeared. Parents recorded the details of the colic symptoms in a diary every day. All these outcomes were modeled simultaneously via a random-effects joint model. RESULTS: Among 100 infants included in the analysis, 48% were female; 91% of all infants were breastfed and 54% of them were born via normal vaginal delivery. In general, the effect of massage therapy on colic symptoms was assessed using the joint model. Our findings illustrated that massaging colicky infants would substantially reduce colic symptoms and increase the sleep duration in babies compared with the rocking group (P<0.001). CONCLUSION: Massage therapy could be considered as an effective method in reducing colic symptoms. Mean of the symptoms dropped significantly in the intervention group compared with that in the rocking group. Our study also represents that a relevant and correct statistical model could result in more reliable findings.

A hierarchical Bayesian tri-variate analysis on factors associated with anthropometric measures in a large sample of children and adolescents: the CASPIAN-IV study.

BACKGROUND: This study aimed to assess determinants of anthropometric measures in a nationally representative sample of Iranian children and adolescents. METHODS: This nationwide study was conducted among 13,280 students, aged 6-18 years, who were randomly selected from 30 provinces in Iran. Anthropometric measures were determined by calibrated instruments. Demographic and socio-economic (SES) variables, lifestyle behaviors, family history of chronic disease and prenatal factors were studied, as well. A hierarchical Bayesian tri-variate analysis was used to assess the factors associated with obesity measures of the body mass index (BMI), waist-to-height ratio (WHtR) and wrist circumference (WrC). RESULTS: The results showed that the BMI was associated with SES score, family history of obesity, family history of diabetes mellitus, physical inactivity, screen time, duration of sleep, breakfast consumption, birth weight, breastfeeding, junk food and place of residence (urban-rural). All these factors were also significantly associated with WrC except for consumption of junk food. Many of these factors had a partial but significant relationship with WHtR. CONCLUSIONS: Various factors contribute to obesity. Preventive and educational programs on manageable factors such as increasing physical activity, eating breakfast and limiting TV or screen time could be helpful in controlling obesity in schoolchildren and reducing associated complications.

Relationship between trajectories of serum albumin levels and technique failure according to diabetic status in peritoneal dialysis patients: A joint modeling approach.

BACKGROUND: In peritoneal dialysis, technique failure is an important metric to be considered. This study was performed in order to identify the relationship between trajectories of serum albumin levels and peritoneal dialysis technique failure on end-stage renal disease patients according to diabetic status. Furthermore, this study was performed to reveal predictors of serum albumin and technique failure simultaneously. METHODS: This retrospective cohort study included 300 (189 non-diabetic and 111 diabetic) end-stage renal disease patients on continuous ambulatory peritoneal dialysis treated in Al-Zahra Hospital, Isfahan, Iran, from May 2005 to March 2015. Bayesian joint modeling was carried out in order to determine the relationship between trajectories of serum albumin levels and peritoneal dialysis technique failure in the patients according to diabetic status. Death from all causes was considered as a competing risk. RESULTS: Using joint modeling approach, a relationship between trajectories of serum albumin with hazard of transfer to hemodialysis was estimated as -0.720 (95% confidence interval [CI], -0.971 to -0.472) for diabetic and -0.784 (95% CI, -0.963 to -0.587) for non-diabetic patients. From our findings it was showed that predictors of low serum albumin over time were time on peritoneal dialysis for diabetic patients and increase in age and time on peritoneal dialysis, history of previous hemodialysis, and lower body mass index in non-diabetic patients. CONCLUSION: The results of current study showed that controlling serum albumin over time in non-diabetic and diabetic patients undergoing continuous ambulatory peritoneal dialysis treatment can decrease risk of adverse outcomes during the peritoneal dialysis period.

Using skew-symmetric mixed models for investigating the effect of different diabetic macular edema treatments by analyzing central macular thickness and visual acuity responses.

BACKGROUND: Diabetic Macular Edema (DME) is one of the major causes of visual loss and increase in central macular thickness (CMT). The aim of this study was to determine the efficacy of a single intravitreal injection of bevacizumab (IVB) alone or in combination with intravitreal triamcinolone acetonide (IVB/IVT) versus macular laser photocoagulation (MPC) as primary treatment for DME when confounders were considered. METHODS: Skew-symmetric bivariate mixed modeling according to best corrected visual acuity (BCVA) and CMT was done on the data of 103 diabetic patients from ophthalmic research center of Labbafinejad medical center (Tehran, Iran) to determine the best DME treatment by adjusting the effect of confounders. RESULTS: Although there was no significant difference between IVB/IVT (p > 0.05), these two treatments increased BCVA and decreased CMT better than MPC (p < 0.05). The following three groups showed better treatment responses: 1) women, 2) patients with more diabetes duration, 3) patients whose CMT were higher and VA were lower at the beginning of the clinical trial. CONCLUSIONS: Using skew-symmetric mixed effect model as updated statistical method in presence of asymmetric or outlier data, we received different results compared to the same investigation on this study by analyzing BCVA and CMT simultaneously. This research demonstrated the effect of IVB alone or in combination with intravitreal IVB/IVT on visual power and decreasing CMT during follow up.