171 research outputs found
Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder
The genetic overlap between mood disorders and cardiometabolic diseases: a systematic review of genome wide and candidate gene studies
© The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.Meta-analyses of genome-wide association studies (meta-GWASs) and candidate gene studies have identified genetic variants associated with cardiovascular diseases, metabolic diseases and mood disorders. Although previous efforts were successful for individual disease conditions (single disease), limited information exists on shared genetic risk between these disorders. This article presents a detailed review and analysis of cardiometabolic diseases risk (CMD-R) genes that are also associated with mood disorders. First, we reviewed meta-GWASs published until January 2016, for the diseases ‘type 2 diabetes, coronary artery disease, hypertension’ and/or for the risk factors ‘blood pressure, obesity, plasma lipid levels, insulin and glucose related traits’. We then searched the literature for published associations of these CMD-R genes with mood disorders. We considered studies that reported a significant association of at least one of the CMD-R genes and ‘depression’ or ‘depressive disorder’ or ‘depressive symptoms’ or ‘bipolar disorder’ or ‘lithium treatment response in bipolar disorder’, or ‘serotonin reuptake inhibitors treatment response in major depression’. Our review revealed 24 potential pleiotropic genes that are likely to be shared between mood disorders and CMD-Rs. These genes include MTHFR, CACNA1D, CACNB2, GNAS, ADRB1, NCAN, REST, FTO, POMC, BDNF, CREB, ITIH4, LEP, GSK3B, SLC18A1, TLR4, PPP1R1B, APOE, CRY2, HTR1A, ADRA2A, TCF7L2, MTNR1B and IGF1. A pathway analysis of these genes revealed significant pathways: corticotrophin-releasing hormone signaling, AMPK signaling, cAMP-mediated or G-protein coupled receptor signaling, axonal guidance signaling, serotonin or dopamine receptors signaling, dopamine-DARPP32 feedback in cAMP signaling, circadian rhythm signaling and leptin signaling. Our review provides insights into the shared biological mechanisms of mood disorders and cardiometabolic diseases
Trends and causes of maternal mortality in Ethiopia during 1990-2013:Findings from the Global Burden of Diseases study 2013
Background: Maternal mortality is noticeably high in sub-Saharan African countries including Ethiopia. Continuous nationwide systematic evaluation and assessment of the problem helps to design appropriate policy and strategy in Ethiopia. This study aimed to investigate the trends and causes of maternal mortality in Ethiopia between 1990 and 2013. Methods: We used the Global Burden of Diseases and Risk factors (GBD) Study 2013 data that was collected from multiple sources at national and subnational levels. Spatio-temporal Gaussian Process Regression (ST-GPR) was applied to generate best estimates of maternal mortality with 95% Uncertainty Intervals (UI). Causes of death were measured using Cause of Death Ensemble modelling (CODEm). The modified UNAIDS EPP/SPECTRUM suite model was used to estimate HIV related maternal deaths. Results: In Ethiopia, a total of 16,740 (95% UI: 14,197, 19,271) maternal deaths occurred in 1990 whereas there were 15,234 (95% UI: 11,378, 19,871) maternal deaths occurred in 2013. This finding shows that Maternal Mortality Ratio (MMR) in Ethiopia was still high in the study period. There was a minimal but insignificant change of MMR over the last 23 years. The results revealed Ethiopia is below the target of Millennium Development Goals (MGDs) related to MMR. The top five causes of maternal mortality in 2013 were other direct maternal causes such as complications of anaesthesia, embolism (air, amniotic fluid, and blood clot), and the condition of peripartum cardiomyopathy (25.7%), complications of abortions (19.6%), maternal haemorrhage (12.2%), hypertensive disorders (10.3%), and maternal sepsis and other maternal infections such as influenza, malaria, tuberculosis, and hepatitis (9.6%). Most of the maternal mortality happened during the postpartum period and majority of the deaths occurred at the age group of 20-29 years. Overall trend showed that there was a decline from 708 per 100,000 live births in 1990 to 497 per 100,000 in 2013. The annual rate of change over these years was-1.6 (95% UI:-2.8 to-0.3). Conclusion: The findings of the study highlight the need for comprehensive efforts using multisectoral collaborations from stakeholders for reducing maternal mortality in Ethiopia. It is worthwhile for policies to focus on postpartum period
The genetic relationship between female reproductive traits and six psychiatric disorders
Female reproductive behaviours have important implications for evolutionary fitness and health of offspring. Here we used the second release of UK Biobank data (N = 220,685) to evaluate the association between five female reproductive traits and polygenic risk scores (PRS) projected from genome-wide association study summary statistics of six psychiatric disorders (N = 429,178). We found that the PRS of attention-deficit/hyperactivity disorder (ADHD) were strongly associated with age at first birth (AFB) (genetic correlation of -0.68 ± 0.03), age at first sexual intercourse (AFS) (-0.56 ± 0.03), number of live births (NLB) (0.36 ± 0.04) and age at menopause (-0.27 ± 0.04). There were also robustly significant associations between the PRS of eating disorder (ED) and AFB (0.35 ± 0.06), ED and AFS (0.19 ± 0.06), major depressive disorder (MDD) and AFB (-0.27 ± 0.07), MDD and AFS (-0.27 ± 0.03) and schizophrenia and AFS (-0.10 ± 0.03). These associations were mostly explained by pleiotropic effects and there was little evidence of causal relationships. Our findings can potentially help improve reproductive health in women, hence better child outcomes. Our findings also lend partial support to the evolutionary hypothesis that causal mutations underlying psychiatric disorders have positive effects on reproductive success
Bivariate genome-wide association analyses of the broad depression phenotype combined with major depressive disorder, bipolar disorder or schizophrenia reveal eight novel genetic loci for depression
Although a genetic basis of depression has been well established in twin studies, identification of genome-wide significant
loci has been difficult. We hypothesized that bivariate analyses of findings from a meta-analysis of genome-wide association
studies (meta-GWASs) of the broad depression phenotype with those from meta-GWASs of self-reported and recurrent
major depressive disorder (MDD), bipolar disorder and schizophrenia would enhance statistical power to identify novel
genetic loci for depression. LD score regression analyses were first used to estimate the genetic correlations of broad
depression with self-reported MDD, recurrent MDD, bipolar disorder and schizophrenia. Then, we performed four bivariate
GWAS analyses. The genetic correlations (rg ± SE) of broad depression with self-reported MDD, recurrent MDD, bipolar
disorder and schizophrenia were 0.79 ± 0.07, 0.24 ± 0.08, 0.53
The burden of HIV/AIDS in Ethiopia from 1990 to 2016: evidence from the Global Burden of Diseases 2016 Study
BACKGROUND: The burden of HIV/AIDS in Ethiopia has not been comprehensively assessed over the last two decades. In this study, we used the 2016 Global Burden of Diseases, Injuries and Risk factors (GBD) data to analyze the incidence, prevalence, mortality and Disability-adjusted Life Years Lost (DALY) rates of Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome (HIV/AIDS) in Ethiopia over the last 26 years. METHODS: The GBD 2016 used a wide range of data source for Ethiopia such as verbal autopsy (VA), surveys, reports of the Federal Ministry of Health and the United Nations (UN) and published scientific articles. The modified United Nations Programme on HIV/AIDS (UNAIDS) Spectrum model was used to estimate the incidence and mortality rates for HIV/AIDS. RESULTS: In 2016, an estimated 36,990 new HIV infections (95% uncertainty interval [UI]: 8775-80262), 670,906 prevalent HIV cases (95% UI: 568,268-798,970) and 19,999 HIV deaths (95% UI: 16426-24412) occurred in Ethiopia. The HIV/AIDS incidence rate peaked in 1995 and declined by 6.3% annually for both sexes with a total reduction of 77% between 1990 and 2016. The annualized HIV/AIDS mortality rate reduction during 1990 to 2016 for both sexes was 0.4%
National disability-adjusted life years(DALYs) for 257 diseases and injuries in Ethiopia, 1990–2015: findings from the global burden of disease study 2015
Background: Disability-adjusted life years (DALYs) provide a summary measure of health and can be a critical input
to guide health systems, investments, and priority-setting in Ethiopia. We aimed to determine the leading causes of
premature mortality and disability using DALYs and describe the relative burden of disease and injuries in Ethiopia.
Methods: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for non-fatal disease burden, cause-specific mortality, and all-cause mortality to derive age-standardized DALYs by sex
for Ethiopia for each year. We calculated DALYs by summing years of life lost due to premature mortality (YLLs) and
years lived with disability (YLDs) for each age group and sex. Causes of death by age, sex, and year were measured
mainly using Causes of Death Ensemble modeling. To estimate YLDs, a Bayesian meta-regression method was used.
We reported DALY rates per 100,000 for communicable, maternal, neonatal, and nutritional (CMNN) disorders,
non-communicable diseases, and injuries, with 95% uncertainty intervals (UI) for Ethiopia.
Results: Non-communicable diseases caused 23,118.1 (95% UI, 17,124.4–30,579.6), CMNN disorders resulted in
20,200.7 (95% UI, 16,532.2–24,917.9), and injuries caused 3781 (95% UI, 2642.9–5500.6) age-standardized DALYs
per 100,000 in Ethiopia in 2015. Lower respiratory infections, diarrheal diseases, and tuberculosis were the top three leading causes of DALYs in 2015, accounting for 2998 (95% UI, 2173.7–4029), 2592.5 (95% UI, 1850.7–3495.1), and 2562.9 (95% UI, 1466.1–4220.7) DALYs per 100,000, respectively. Ischemic heart disease and cerebrovascular disease were the fourth and fifth leading causes of age-standardized DALYs, with rates of 2535.7 (95% UI, 1603.7–3843.2) and 2159.9 (95% UI, 1369.7–3216.3) per 100,000, respectively. The following causes showed a reduction of 60% or more over the last 25 years: lower respiratory infections, diarrheal diseases, tuberculosis, neonatal encephalopathy, preterm birth complications, meningitis, malaria, protein-energy malnutrition, iron-deficiency anemia, measles, war and legal intervention, and maternal hemorrhage
National mortality burden due to communicable, non-communicable, and other diseases in Ethiopia, 1990–2015: findings from the Global Burden of Disease Study 2015
Background: Ethiopia lacks a complete vital registration system that would assist in measuring disease burden and risk factors. We used the Global Burden of Diseases, Injuries, and Risk factors 2015 (GBD 2015) estimates to describe the mortality burden from communicable, non-communicable, and other diseases in Ethiopia over the last 25 years.
Methods: GBD 2015 mainly used cause of death ensemble modeling to measure causes of death by age, sex, and year for 195 countries. We report numbers of deaths and rates of years of life lost (YLL) for communicable, maternal, neonatal, and nutritional (CMNN) disorders, non-communicable diseases (NCDs), and injuries with 95% uncertainty intervals (UI) for Ethiopia from 1990 to 2015.
Results: CMNN causes of death have declined by 65% in the last two-and-a-half decades. Injury-related causes of death have also decreased by 70%. Deaths due to NCDs declined by 37% during the same period. Ethiopia showed a faster decline in the burden of four out of the five leading causes of age-standardized premature mortality rates when compared to the overall sub-Saharan African region and the Eastern sub-Saharan African region: lower respiratory infections, tuberculosis, HIV/AIDS, and diarrheal diseases; however, the same could not be said for ischemic heart disease and other NCDs. Non-communicable diseases, together, were the leading causes of age-standardized mortality rates, whereas CMNN diseases were leading causes of premature mortality in 2015. Although lower respiratory infections, tuberculosis, and diarrheal disease were the leading causes of age-standardized death rates, they showed major declines from 1990 to 2015. Neonatal encephalopathy, iron-deficiency anemia, protein-energy malnutrition, and preterm birth complications also showed more than a 50% reduction in burden. HIV/AIDS-related deaths have also decreased by 70% since 2005. Ischemic heart disease, hemorrhagic stroke, and ischemic stroke were among the top causes of premature mortality and age-standardized death rates in Ethiopia in 2015.
Conclusions: Ethiopia has been successful in reducing deaths related to communicable, maternal, neonatal, and nutritional deficiency diseases and injuries by 65%, despite unacceptably high maternal and neonatal mortality rates. However, the country’s performance regarding non-communicable diseases, including cardiovascular disease, diabetes, cancer, and chronic respiratory disease, was minimal, causing these diseases to join the leading causes of premature mortality and death rates in 2015. While the country is progressing toward universal health coverage, prevention and control strategies in Ethiopia should consider the double burden of common infectious diseases and non-communicable diseases: lower respiratory infections, diarrhea, tuberculosis, HIV/AIDS, cardiovascular disease, cancer, and diabetes. Prevention and control strategies should also pay special attention to the leading causes of premature mortality and death rates caused by non-communicable diseases: cardiovascular disease, cancer, and diabetes. Measuring further progress requires a data revolution in generating, managing, analyzing, and using data for decision-making and the creation of a full vital registration system in the country
Incidence, prevalence and mortality rates of malaria in Ethiopia from 1990 to 2015: analysis of the global burden of diseases 2015
Background: In Ethiopia there is no complete registration system to measure disease burden and risk factors accurately. In this study, the 2015 Global Burden of Diseases, Injuries and Risk factors (GBD) data were used to analyse the incidence, prevalence and mortality rates of malaria in Ethiopia over the last 25 years.
Methods: GBD 2015 used verbal autopsy (VA) surveys, reports, and published scientific articles to estimate the burden of malaria in Ethiopia. Age and gender-specific causes of death for malaria were estimated using Cause of Death Ensemble Modelling (CODEm).
Results: The number of new cases of malaria declined from 2.8 million (95% uncertainty interval (UI): 1.4-4.5million) in 1990 to 621,345 (95% UI: 462,230-797,442) in 2015. Malaria caused an estimated 30,323.9 deaths (95% UI: 11,533.3-61,215.3) in 1990 and 1,561.7 deaths (95% UI: 752.8-2,660.5) in 2015, a 94.8% reduction over the 25 years. Age-standardized mortality rate of malaria has declined by 96.5% between 1990 and 2015 with an annual rate of change (ARC) of 13.4%. Age-standardized malaria incidence rate among all ages and gender declined by 88.7% between 1990 and 2015. The number of disability-adjusted life years lost (DALY) due to malaria decreased from 2.2 million (95% UI: 0.76-4.7 million) in 1990 to 0.18 million (95% UI: 0.12-0.26 million) in 2015, with a total reduction 91.7%. Similarly, age-standardized DALY rate declined by 94.8% during the same period.
Conclusions: Ethiopia has achieved a 50% reduction target of malaria of the Millennium Development Goals (MDGs). The country should strengthen its malaria control and treatment strategies to achieve the Sustainable Development Goals (SDG)
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