| 1. |
- Wilman, H. R., et al.
(författare)
-
Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
-
Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
|
|
| 2. |
- Azimoh, C. L., et al.
(författare)
-
Replicability and scalability of mini-grid solution to rural electrification programs in sub-Saharan Africa
- 2017
-
Ingår i: Renewable Energy. - : Elsevier BV. - 0960-1481. ; 106, s. 222-231
-
Tidskriftsartikel (refereegranskat)abstract
- The assessment of off-grid electrification programs in developing countries largely based on mini-grid and solar home system (SHS) has shown that they are faced with low development imparts and sustainability challenges, which has resulted in failure of many projects. This study provides solutions on how to surmount these challenges, leaning on the experience of a hybrid solar-diesel mini-grid at Tsumkwe village in Namibia. It provides analyses of a case study based on empirical evidence from field studies, interviews of representatives of households, public institutions and energy providers. In addition, it investigates the technical challenges and economic impacts of the electrification program. HOMER™ and MATLAB™ models were used in the analysis and investigations. The findings show that despite the challenges, the system has been sustained because it keyed into an existing structure with growth potentials. The progressive tariff system adopted by the government helped to cushion costs and allow low income households in the energy matrix. Adoption of strict maintenance measures, and implementation of energy efficiency measures prior to the commissioning of the program, resulted in the reduction of costs. The success elements identified in this study could be extrapolated in other sub-Saharan African countries if the challenges are properly addressed.
|
|
