| 1. |
- Schunkert, Heribert, et al.
(författare)
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Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333
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Tidskriftsartikel (refereegranskat)abstract
- We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
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| 2. |
- Jay, Flora, et al.
(författare)
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Anisotropic Isolation by Distance : The Main Orientations of Human Genetic Differentiation
- 2013
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 30:3, s. 513-525
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Tidskriftsartikel (refereegranskat)abstract
- Genetic differentiation among human populations is greatly influenced by geography due to the accumulation of local allele frequency differences. However, little is known about the possibly different increment of genetic differentiation along the different geographical axes (north-south, east-west, etc.). Here, we provide new methods to examine the asymmetrical patterns of genetic differentiation. We analyzed genome-wide polymorphism data from populations in Africa (n = 29), Asia (n = 26), America (n = 9), and Europe (n = 38), and we found that the major orientations of genetic differentiation are north-south in Europe and Africa, and east-west in Asia, but no preferential orientation was found in the Americas. Additionally, we showed that the localization of the individual geographic origins based on single nucleotide polymorphism data was not equally precise along all orientations. Confirming our findings, we obtained that, in each continent, the orientation along which the precision is maximal corresponds to the orientation of maximum differentiation. Our results have implications for interpreting human genetic variation in terms of isolation by distance and spatial range expansion processes. In Europe, for instance, the precise northnorthwest-southsoutheast axis of main European differentiation cannot be explained by a simple Neolithic demic diffusion model without admixture with the local populations because in that case the orientation of greatest differentiation should be perpendicular to the direction of expansion. In addition to humans, anisotropic analyses can guide the description of genetic differentiation for other organisms and provide information on expansions of invasive species or the processes of plant dispersal.
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| 3. |
- Olhager, Elisabeth, et al.
(författare)
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Preterm lambs given intravenous dopamine show increased dopamine in their cerebrospinal fluid
- 2014
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 103:3, s. 337-342
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Tidskriftsartikel (refereegranskat)abstract
- AimDopamine is used as an inotropic medication in preterm infants. The preterm human blood brain barrier (BBB) is permeable to intravascular dopamine, and the impact of exogenous dopamine on the preterm brain remains unknown. The preterm lamb model may be suitable for studying the cerebral impact of dopamine therapy whether its BBB permeability is similar to preterm human infants. We aimed to examine BBB permeability to exogenous dopamine in the preterm lamb, by measuring dopamine levels in the cerebrospinal fluid (CSF). MethodsNine preterm foetal lambs (125-130days, term=147days) were given either dopamine at 10g/kg/min (dopamine, n=4) or saline (control, n=5). CSF, and plasma samples were taken for dopamine assay. ResultsThe median (range) baseline CSF dopamine level for the combined control and dopamine groups (n=9) was 0.10(0.03-0.16)ng/mL, and baseline plasma dopamine was 0.30(0.13-0.84) ng/mL. The dopamine lambs showed increase in CSF dopamine to 3.91(1.87-11.35)ng/mL with plasma dopamine increased to 14.2 (9.1-57.9)ng/mL. No change was found in the control lambs. ConclusionIn the preterm lamb, the BBB permeability and pharmacokinetics to dopamine infusion are similar to findings in the preterm human infant, supporting applicability of the preterm lamb model for studying effects of dopamine infusion in the preterm human brain.
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| 4. |
- Schlebusch, Carina M., et al.
(författare)
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Genomic Variation in Seven Khoe-San Groups Reveals Adaptation and Complex African History
- 2012
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 338:6105, s. 374-379
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Tidskriftsartikel (refereegranskat)abstract
- The history of click-speaking Khoe-San, and African populations in general, remains poorly understood. We genotyped ∼2.3 million SNPs in 220 southern Africans and found that the Khoe-San diverged from other populations ≥100,000 years ago, but structure within the Khoe-San dated back to about 35,000 years ago. Genetic variation in various sub-Saharan populations did not localize the origin of modern humans to a single geographic region within Africa; instead, it indicated a history of admixture and stratification. We found evidence of adaptation targeting muscle function and immune response, potential adaptive introgression of UV-light protection, and selection predating modern human diversification involving skeletal and neurological development. These new findings illustrate the importance of African genomic diversity in understanding human evolutionary history.
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