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- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 5. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 6. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 7. |
- Kariuki, Symon M., et al.
(författare)
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Prevalence and factors associated with convulsive status epilepticus in Africans with epilepsy
- 2015
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 84:18, s. 1838-1845
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Tidskriftsartikel (refereegranskat)abstract
- Objective:We conducted a community survey to estimate the prevalence and describe the features, risk factors, and consequences of convulsive status epilepticus (CSE) among people with active convulsive epilepsy (ACE) identified in a multisite survey in Africa.Methods:We obtained clinical histories of CSE and neurologic examination data among 1,196 people with ACE identified from a population of 379,166 people in 3 sites: Agincourt, South Africa; Iganga-Mayuge, Uganda; and Kilifi, Kenya. We performed serologic assessment for the presence of antibodies to parasitic infections and HIV and determined adherence to antiepileptic drugs. Consequences of CSE were assessed using a questionnaire. Logistic regression was used to identify risk factors.Results:The adjusted prevalence of CSE in ACE among the general population across the 3 sites was 2.3 per 1,000, and differed with site (p < 0.0001). Over half (55%) of CSE occurred in febrile illnesses and focal seizures were present in 61%. Risk factors for CSE in ACE were neurologic impairments, acute encephalopathy, previous hospitalization, and presence of antibody titers to falciparum malaria and HIV; these differed across sites. Burns (15%), lack of education (49%), being single (77%), and unemployment (78%) were common in CSE; these differed across the 3 sites. Nine percent with and 10% without CSE died.Conclusions:CSE is common in people with ACE in Africa; most occurs with febrile illnesses, is untreated, and has focal features suggesting preventable risk factors. Effective prevention and the management of infections and neurologic impairments may reduce the burden of CSE in ACE.
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| 8. |
- Ibinda, Fredrick, et al.
(författare)
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Magnitude and factors associated with nonadherence to antiepileptic drug treatment in Africa : a cross-sectional multisite study
- 2017
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Ingår i: Epilepsia Open. - : John Wiley & Sons. - 2470-9239. ; 2:2, s. 226-235
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The epilepsy treatment gap is large in low- and middle-income countries, but the reasons behind nonadherence to treatment with antiepileptic drugs (AEDs) across African countries remain unclear. We investigated the extent to which AEDs are not taken and associated factors in people with active convulsive epilepsy (ACE) identified in cross-sectional studies conducted in five African countries.Methods: We approached 2,192 people with a confirmed diagnosis of ACE for consent to give blood voluntarily. Participants were asked if they were taking AEDs, and plasma drug concentrations were measured using a fluorescence polarization immunoassay analyzer. Information about possible risk factors was collected using questionnaire-based clinical interviews. We determined factors associated with nonadherence to AED treatment in children and adults, as measured by detectable and optimal levels, using multilevel logistic regression.Results: In 1,303 samples assayed (43.7% were children), AEDs were detected in 482, but only 287 had optimal levels. Of the 1,303 samples, 532 (40.8%) were from people who had reported they were on AEDs. The overall prevalence of nonadherence to treatment was 63.1% (95% confidence interval [CI] 60.5–65.6%) as measured by detectable AED levels and 79.1% (95% CI 73.3–84.3%) as measured by optimal AED levels; self-reported nonadherence was 65.1% (95% CI 45.0–79.5%). Nonadherence was significantly (p < 0.001) more common among the children than among adults for optimal and detectable levels of AEDs, as was the self-reported nonadherence. In children, lack of previous hospitalization and learning difficulties were independently associated with nonadherence to treatment. In adults, history of delivery at home, absence of burn marks, and not seeking traditional medicine were independently associated with the nonadherence to AED treatment.Significance: Only about 20% of people with epilepsy benefit fully from antiepileptic drugs in sub-Saharan Africa, according to optimum AEDs levels. Children taking AEDs should be supervised to promote compliance.
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| 9. |
- Jones, C., et al.
(författare)
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Experiences and needs of parents of young children with active epilepsy: A population-based study
- 2019
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Ingår i: Epilepsy and Behavior. - : Elsevier BV. - 1525-5050. ; 90, s. 37-44
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to gain a comprehensive understanding of the experiences and needs of parents of young children with epilepsy from a total population sample. The parents (mothers (n = 38), fathers (n = 9)) of 40/53 (75% of total population) young children (1–7 years; 23 males, 17 females) with ‘active’ epilepsy (had a seizure in the last year or taking Anti-epileptic drugs (AEDs)) were interviewed either in person or over the telephone using a semistructured interview schedule. The families were resident in the south of the UK. The interviews were audio-recorded, transcribed, and coded using thematic analysis. Thematic analysis revealed six main themes: diagnostic journey, parental perception of epilepsy management, awareness and impact of associated neurobehavioral difficulties, inconsistent availability of therapeutic and educational supports, impact on family functioning, and need for parental support. Parents reported often having difficulty accessing a professional knowledgeable about epilepsy. While parents were generally satisfied with the initial information they received about seizures and their management, they reported that the association between epilepsy and neurobehavioral issues was often not broached. These developmental/behavioral difficulties often had a bigger impact on child wellbeing and family functioning, but provision of therapeutic and educational supports for the difficulties was often very patchy. Parents noted that early onset epilepsy and associated neurobehavioral difficulties often have a very significant impact on family functioning including increased restrictions on family activities and increased financial burden. Parents would like informational and emotional support to extend beyond the time of epilepsy diagnosis. There is a clear need for comprehensive childhood epilepsy services to include provision for identification and management of child neurobehavioral needs and a focus on family-centered care. © 2018 Elsevier Inc.
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| 10. |
- Kariuki, Symon M., et al.
(författare)
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Electroencephalographic features of convulsive epilepsy in Africa : A multicentre study of prevalence, pattern and associated factors
- 2016
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457 .- 1872-8952. ; 127:2, s. 1099-1107
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We investigated the prevalence and pattern of electroencephalographic (EEG) features of epilepsy and the associated factors in Africans with active convulsive epilepsy (ACE).Methods: We characterized electroencephalographic features and determined associated factors in a sample of people with ACE in five African sites. Mixed-effects modified Poisson regression model was used to determine factors associated with abnormal EEGs.Results: Recordings were performed on 1426 people of whom 751 (53%) had abnormal EEGs, being an adjusted prevalence of 2.7 (95% confidence interval (95% CI), 2.5–2.9) per 1000. 52% of the abnormal EEG had focal features (75% with temporal lobeinvolvement). The frequency and pattern of changes differed with site. Abnormal EEGs were associated with adverse perinatal events (risk ratio (RR) = 1.19 (95% CI, 1.07–1.33)), cognitive impairments (RR = 1.50 (95% CI, 1.30–1.73)), use of anti-epilepticdrugs (RR = 1.25 (95% CI, 1.05–1.49)), focal seizures (RR = 1.09 (95% CI, 1.00–1.19)) and seizure frequency (RR = 1.18 (95% CI, 1.10–1.26) for daily seizures; RR = 1.22 (95% CI, 1.10–1.35) for weekly seizures and RR = 1.15 (95% CI, 1.03–1.28) for monthly seizures)).Conclusions: EEG abnormalities are common in Africans with epilepsy and are associated with preventable risk factors.Significance: EEG is helpful in identifying focal epilepsy in Africa, where timing of focal aetiologies is problematic and there is a lack of neuroimaging services.
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