Project description:BackgroundMixed linear models (MLM) have been widely used to account for population structure in case-control genome-wide association studies, the status being analyzed as a quantitative phenotype. Chen et al. proved in 2016 that this method is inappropriate in some situations and proposed GMMAT, a score test for the mixed logistic regression (MLR). However, this test does not produces an estimation of the variants' effects. We propose two computationally efficient methods to estimate the variants' effects. Their properties and those of other methods (MLM, logistic regression) are evaluated using both simulated and real genomic data from a recent GWAS in two geographically close population in West Africa.ResultsWe show that, when the disease prevalence differs between population strata, MLM is inappropriate to analyze binary traits. MLR performs the best in all circumstances. The variants' effects are well evaluated by our methods, with a moderate bias when the effect sizes are large. Additionally, we propose a stratified QQ-plot, enhancing the diagnosis of p values inflation or deflation when population strata are not clearly identified in the sample.ConclusionThe two proposed methods are implemented in the R package milorGWAS available on the CRAN. Both methods scale up to at least 10,000 individuals. The same computational strategies could be applied to other models (e.g. mixed Cox model for survival analysis).
Project description:BackgroundUnmet need for family planning is high (30%) in Ghana. Reducing unmet need for family planning will reduce the high levels of unintended pregnancies, unsafe abortions, maternal and neonatal morbidity and mortality. The purpose of this study was to examine factors that are associated with unmet need for family planning to help scale up the uptake of family planning services in Ghana.MethodsThis cross sectional descriptive and inferential study involved secondary data analysis of women in the reproductive age (15-49 years) from the Ghana Demographic and Health Survey 2014 data. The outcome variable was unmet need for family planning which was categorized into three as no unmet need, unmet need for limiting and unmet need for spacing. Chi-squared test statistic and bivariate multilevel multinomial mixed effects logistic regression model were used to determine significant variables which were included for the multivariable multilevel multinomial mixed effects logistic regression model. All significant variables (p < 0.05) based on the bivariate analysis were included in the multinomial mixed effects logistic regression model via model building approach.ResultsWomen who fear contraceptive side effects were about 2.94 (95% CI, 2.28, 3.80) and 2.58 (95% CI, 2.05, 3.24) times more likely to have an unmet need for limiting and spacing respectively compared to those who do not fear side effects. Respondents' age was a very significant predictor of unmet need for family planning. There was very high predictive probability among 45-49 year group (0.86) compared to the 15-19 year group (0.02) for limiting. The marginal predictive probability for spacing changed significantly from 0.74 to 0.04 as age changed from 15 to 19 to 45-49 years. Infrequent sexual intercourse, opposition from partners, socio-economic (wealth index, respondents educational level, respondents and partner's occupation) and cultural (religion and ethnicity) were all significant determinants of both unmet need for limiting and spacing.ConclusionsThis study reveals that fear of side effect, infrequent sex, age, ethnicity, partner's education and region were the most highly significant predictors of both limiting and spacing. These factors must be considered in trying to meet the unmet need for family planning.
Project description:Listeria outbreaks and food recalls is on the raise globally. Milk particularly is highly susceptible to Listeria as its production and storage adequately support Listeria growth. The extent of milk contamination with Listeria monocytogenes (Lm) and preventative actions to halt milk associated outbreaks in Africa are unknown. Hence, this study aimed at assessing the national and subregional prevalence of Lm in milk in Africa and identify impacting factors via generalized logistic mixed-effects (GLMEs) and meta-regression modelling. Lm-milk-specific data acquired from primary studies according to standard protocol were fitted using a GLMEs. The GLMEs was subjected to leave-one-study-out-cross-validation (LOSOCV). Factors impacting Lm prevalence in milk were assayed via a 1000-permutation-assisted meta-regression-modelling. The pooled prevalence of Lm in milk in Africa was 4.35% [2.73-6.86] with a prediction interval (PI) of 0.14-59.86% and LOSOCV value of 2.43% [1.62-3.62; PI: 0.32-16.11%]. Western Africa had the highest prevalence [20.13%, 4.13-59.59], then Southern Africa [5.85%, 0.12-75.72], Northern Africa [4.67%, 2.82-7.64], Eastern Africa [1.91%, 0.64-5.55], and there was no record from Central Africa. In term of country, Lm prevalence in milk significantly (p < 0.01) varied from 0.00 to 90.00%. Whereas the Lm prevalence was negligibly different (p = 0.77) by milk type, raw-milk had the highest prevalence [5.26%], followed by fermented-milk [4.76%], boiled-milk [2.90%], pasteurized-milk [1.64%], and powdered-milk [1.58%]. DNA extraction approach did not significantly (p = 0.07) affect Lm prevalence (Boiling [7.82%] versus Kit [7.24%]) as well as Lm detection method (p = 0.10; (ACP [3.64%] vs. CP [8.92%] vs. CS [2.27%] vs. CSP [6.82%]). Though a bivariate/multivariate combination of all tested variables in meta-regression explained 19.68-68.75% (R2) variance in Lm prevalence in milk, N, nation, and subregion singly/robustly accounted for 17.61% (F1;65 = 7.5994; p = 0.005), 63.89% (F14;52 = 4.2028; p = 0.001), and 16.54% (F3;63 = 3.4743; p = 0.026), respectively. In conclusion, it is recommended that adequate sample size should be prioritized in monitoring Lm in milk to prevent spuriously high or low prevalence to ensure robust, plausible, and credible estimate. Also, national efforts/interests and commitments to Lm monitoring should be awaken.
Project description:BackgroundDiversified diet in childhood has irreplaceable role for optimal growth. However, multi-level factors related to low animal source food consumption among children were poorly understood in Ethiopia, where such evidences are needed for decision making.ObjectivesTo investigate the magnitude and individual- and community-level predictors of animal source food (ASF) consumption among children aged 6-23 months in Ethiopia.MethodsWe utilized a cross-sectional pooled data from 2016/19 Ethiopia Demographic and Health Surveys. A stratified two-stage cluster design was employed to select households with survey weights were applied to account for complex sample design. We fitted mixed-effects logit regression models on 4,423 children nested within 645 clusters. The fixed effect models were fitted and expressed as adjusted odds ratio with their 95% confidence intervals and measures of variation were explained by intra-class correlation coefficients, median odds ratio and proportional change in variance. The deviance information criterion and Akaike information Criterion were used as model fitness criteria.Resultin Ethiopia, only 22.7% (20.5%-23.9%) of children aged 6-23 months consumed ASF. Younger children aged 6-8 months (AOR = 3.1; 95%CI: 2.4-4.1), home delivered children (AOR = 1.8; 1.4-2.3), from low socioeconomic class (AOR = 2.43; 1.7-3.5); low educational level of mothers (AOR = 1.9; 95%CI: 1.48-2.45) and children from multiple risk pregnancy were significant predictors of low animal source consumption at individual level. While children from high community poverty level (AOR = 1.53; 1.2-1.95); rural residence (AOR = 2.2; 95%CI: 1.7-2.8) and pastoralist areas (AOR = 5.4; 3.4-8.5) significantly predict animal source food consumption at community level. About 38% of the variation of ASF consumption is explained by the combined predictors at the individual and community-level while 17.8% of the variation is attributed to differences between clusters.ConclusionsThis study illustrates that the current ASF consumption among children is poor and a multiple interacting individual- and community level factors determine ASF consumption. In designing and implementing nutritional interventions addressing diversified diet consumption shall give a due consideration and account for these potential predictors of ASF consumption.
Project description:Rotaviruses (RV) are important causes of diarrhea in animals, especially in domestic animals. Of the 9 RV species, rotavirus A, B, and C (RVA, RVB, and RVC, respectively) had been established as important causes of diarrhea in pigs. The Minnesota Veterinary Diagnostic Laboratory receives swine stool samples from North America to determine the etiologic agents of disease. Between November 2009 and October 2011, 7,508 samples from pigs with diarrhea were submitted to determine if enteric pathogens, including RV, were present in the samples. All samples were tested for RVA, RVB, and RVC by real time RT-PCR. The majority of the samples (82%) were positive for RVA, RVB, and/or RVC. To better understand the risk factors associated with RV infections in swine diagnostic samples, three-level mixed-effects logistic regression models (3L-MLMs) were used to estimate associations among RV species, age, and geographical variability within the major swine production regions in North America. The conditional odds ratios (cORs) for RVA and RVB detection were lower for 1-3 day old pigs when compared to any other age group. However, the cOR of RVC detection in 1-3 day old pigs was significantly higher (p < 0.001) than pigs in the 4-20 days old and >55 day old age groups. Furthermore, pigs in the 21-55 day old age group had statistically higher cORs of RV co-detection compared to 1-3 day old pigs (p < 0.001). The 3L-MLMs indicated that RV status was more similar within states than among states or within each region. Our results indicated that 3L-MLMs are a powerful and adaptable tool to handle and analyze large-hierarchical datasets. In addition, our results indicated that, overall, swine RV epidemiology is complex, and RV species are associated with different age groups and vary by regions in North America.
Project description:BACKGROUND:Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease, whose exact cause remains unclear. A wide range of risk factors has been proposed that helps understanding potential disease pathogenesis. However, there is little consistency for many risk factor associations, thus we undertook an exploratory study of risk factors using data from the UK ME/CFS Biobank participants. We report on risk factor associations in ME/CFS compared with multiple sclerosis participants and healthy controls. METHODS:This was a cross-sectional study of 269 people with ME/CFS, including 214 with mild/moderate and 55 with severe symptoms, 74 people with multiple sclerosis (MS), and 134 healthy controls, who were recruited from primary and secondary health services. Data were collected from participants using a standardised written questionnaire. Data analyses consisted of univariate and multivariable regression analysis (by levels of proximity to disease onset). RESULTS:A history of frequent colds (OR = 8.26, P <= 0.001) and infections (OR = 25.5, P = 0.015) before onset were the strongest factors associated with a higher risk of ME/CFS compared to healthy controls. Being single (OR = 4.41, P <= 0.001), having lower income (OR = 3.71, P <= 0.001), and a family history of anxiety is associated with a higher risk of ME/CFS compared to healthy controls only (OR = 3.77, P < 0.001). History of frequent colds (OR = 6.31, P < 0.001) and infections before disease onset (OR = 5.12, P = 0.005), being single (OR = 3.66, P = 0.003) and having lower income (OR = 3.48, P = 0.001), are associated with a higher risk of ME/CFS than MS. Severe ME/CFS cases were associated with lower age of ME/CFS onset (OR = 0.63, P = 0.022) and a family history of neurological illness (OR = 6.1, P = 0.001). CONCLUSIONS:Notable differences in risk profiles were found between ME/CFS and healthy controls, ME/CFS and MS, and mild-moderate and severe ME/CFS. However, we found some commensurate overlap in risk associations between all cohorts. The most notable difference between ME/CFS and MS in our study is a history of recent infection prior to disease onset. Even recognising that our results are limited by the choice of factors we selected to investigate, our findings are consistent with the increasing body of evidence that has been published about the potential role of infections in the pathogenesis of ME/CFS, including common colds/flu.
Project description:ObjectivesGlycaemic control in children and adolescents with type 1 diabetes mellitus can be challenging, complex and influenced by many factors. This study aimed to identify patient characteristics that were predictive of satisfactory glycaemic control in the paediatric population using a logistic regression mixed-effects (population) modelling approach.MethodsThe data were obtained from 288 patients aged between 1 and 22 years old recorded retrospectively over 3 years (1852 HbA1c observations). HbA1c status was categorised as 'satisfactory' or 'unsatisfactory' glycaemic control, using an a priori cut-off value of HbA1c ≥ 9% (75 mmol/mol), as used routinely by the hospital's endocrine paediatricians. Patients' characteristics were tested as covariates in the model as potential predictors of glycaemic control.ResultsThere were three patient characteristics identified as having a significant influence on glycaemic control: HbA1c measurement at the beginning of the observation period (Odds Ratio (OR) = 0.30 per 1% HbA1c increase, 95% confidence interval (CI) = 0.20-0.41); Age (OR = 0.88 per year increase, 95% CI = 0.80-0.94), and fractional disease duration (disease duration/age, OR = 0.80 per 0.10 increase, 95% CI = 0.66-0.93) were collectively identified as factors contributing significantly to lower the probability of satisfactory glycaemic control.ConclusionsThe study outcomes may prove useful for identifying paediatric patients at risk of having unsatisfactory glycaemic control, and who could require more extensive monitoring, support, or targeted interventions.
Project description:BackgroundEtiologies of congenital microphthalmia and anophthalmia are unclear and commonly thought to be homogenous. To test if risk factors are similar for these two diseases, we compared the risk factors between congenital microphthalmia and anophthalmia in a large Chinese cohort.MethodsA total of 347 patients with congenital microphthalmia or anophthalmia diagnosed by magnetic resonance imaging (MRI), computed tomography (CT) or ultrasound from 2011 to 2018 were enrolled. Patients' clinical information, used as potential risk factors, was retrospectively collected. A multivariable logistic regression model was used to estimate odds ratios (OR) and 95% confidence intervals (CI).ResultsA total of 347 patients were affected by congenital microphthalmia or anophthalmia. A total of 324 cases were microphthalmia, and 23 cases were anophthalmia. Structural abnormalities, mother's age at initial pregnancy, whether the mother drinks, whether the mother was diseased during pregnancy and whether the father has systemic disease passed the univariate test. In the multivariable logistic regression model, whether the mother was diseased during pregnancy (OR =2.804, P=0.023) and whether the father had systemic disease (OR =4.795, P=0.027) are significant risk factors for anophthalmia over microphthalmia. Influenza or common cold infection accounted most of the mother's diseases during pregnancy.ConclusionsMothers with diseases, mainly influenza or common cold infection, during pregnancy are more likely to have baby with anophthalmia than microphthalmia. Our study indicated that there might be different etiologies for anophthalmia and microphthalmia.
Project description:Logistic regression analysis is a statistical technique to evaluate the relationship between various predictor variables (either categorical or continuous) and an outcome which is binary (dichotomous). In this article, we discuss logistic regression analysis and the limitations of this technique.