| 11. |
- Lao, O., et al.
(author)
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Correlation between Genetic and Geographic Structure in Europe
- 2008
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In: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 18:16, s. 1241-1248
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Journal article (peer-reviewed)abstract
- Understanding the genetic structure of the European population is important, not only from a historical perspective, but also for the appropriate design and interpretation of genetic epidemiological studies. Previous population genetic analyses with autosomal markers in Europe either had a wide geographic but narrow genomic coverage [1, 2], or vice versa [3-6]. We therefore investigated Affymetrix GeneChip 500K genotype data from 2,514 individuals belonging to 23 different subpopulations, widely spread over Europe. Although we found only a low level of genetic differentiation between subpopulations, the existing differences were characterized by a strong continent-wide correlation between geographic and genetic distance. Furthermore, mean heterozygosity was larger, and mean linkage disequilibrium smaller, in southern as compared to northern Europe. Both parameters clearly showed a clinal distribution that provided evidence for a spatial continuity of genetic diversity in Europe. Our comprehensive genetic data are thus compatible with expectations based upon European population history, including the hypotheses of a south-north expansion and/or a larger effective population size in southern than in northern Europe. By including the widely used CEPH from Utah (CEU) samples into our analysis, we could show that these individuals represent northern and western Europeans reasonably well, thereby confirming their assumed regional ancestry. © 2008 Elsevier Ltd. All rights reserved.
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| 12. |
- Nilsson, Lars-Göran, et al.
(author)
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Cognitive test battery of CASCADE : Tasks and data.
- 2005
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In: Aging, Neuropsychology and Cognition. - 1382-5585. ; 12:1, s. 32-56
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Journal article (peer-reviewed)abstract
- This paper presents the cognitive test battery used in the CASCADE Study (Cardiovascular Determinants of Dementia) for examining the consequences of cerebral white matter lesions and atrophy. The test battery includes nine different tasks assessing memory, executive function, and global cognitive function. Three episodic memory tasks were used in combinations to assess the role of attention and speed on encoding. Estimates of short- and long-term memory capacity were also derived from these three memory tasks. Semantic memory production / frontal lobe functions were assessed by means of a word fluency test. The Letter Digit Substitution test and the Stroop test were used to assess speed of processing and attention. Motor speed was measured with the Purdue Pegboard test, and global cognitive function was assessed by the Mini Mental State Examination. Overall performance data for the whole CASCADE sample and for each of eight study centers are presented for each test. Possible reasons for performance differences among study centers are discussed.
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| 13. |
- Aulchenko, Yurii S, et al.
(author)
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Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
- 2009
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:1, s. 47-55
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Journal article (peer-reviewed)abstract
- Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
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| 14. |
- Estrada, Karol, et al.
(author)
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A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation.
- 2009
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In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 18:18, s. 3516-24
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Journal article (peer-reviewed)abstract
- Northwestern Europeans are among the tallest of human populations. The increase in body height in these people appears to have reached a plateau, suggesting the ubiquitous presence of an optimal environment in which genetic factors may have exerted a particularly strong influence on human growth. Therefore, we performed a genome-wide association study (GWAS) of body height using 2.2 million markers in 10 074 individuals from three Dutch and one German population-based cohorts. Upon genotyping, the 12 most significantly height-associated single nucleotide polymorphisms (SNPs) from this GWAS in 6912 additional individuals of Dutch and Swedish origin, a genetic variant (rs6717918) on chromosome 2q37.1 was found to be associated with height at a genome-wide significance level (P(combined) = 3.4 x 10(-9)). Notably, a second SNP (rs6718438) located approximately 450 bp away and in strong LD (r(2) = 0.77) with rs6717918 was previously found to be suggestive of a height association in 29 820 individuals of mainly northwestern European ancestry, and the over-expression of a nearby natriuretic peptide precursor type C (NPPC) gene, has been associated with overgrowth and skeletal anomalies. We also found a SNP (rs10472828) located on 5p14 near the natriuretic peptide receptor 3 (NPR3) gene, encoding a receptor of the NPPC ligand, to be associated with body height (P(combined) = 2.1 x 10(-7)). Taken together, these results suggest that variation in the C-type natriuretic peptide signaling pathway, involving the NPPC and NPR3 genes, plays an important role in determining human body height.
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| 15. |
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| 16. |
- Koopman, G, et al.
(author)
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Acute-phase CD4+ T-cell proliferation and CD152 upregulation predict set-point virus replication in vaccinated simian-human immunodeficiency virus strain 89.6p-infected macaques
- 2009
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In: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 90:Pt 4, s. 915-926
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Journal article (peer-reviewed)abstract
- Human immunodeficiency virus (HIV) infection in humans and simian immunodeficiency virus (SIV) infection in macaques are accompanied by a combined early loss of CCR5 (CD195)-expressing CD4+ memory T cells, loss of T-helper function and T-cell hyperactivation, which have all been associated with development of high virus load and disease progression. Here, a cohort of vaccinated simian–human immunodeficiency virus strain 89.6p (SHIV89.6p)-infected rhesus macaques, where preferential depletion of these memory T-cell subsets does not take place and CD4+ T cells are relatively well maintained, was used to study the role of hyperactivation as an independent factor in the establishment of set-point virus load. In the acute phase of the infection, a transient loss of CD4+ T cells, as well as strong increases in expression of proliferation and activation markers on CD4+ and CD8+ T cells, together with CD152 expression on CD4+ T cells, were observed. Peak expression levels of these markers on CD4+ T cells, but not on CD8+ T cells, were correlated with high virus replication in the chronic phase of the infection. In addition, the peak expression level of these markers was correlated inversely with acute-phase, but not chronic-phase, HIV/SIV-specific gamma interferon responses. These data highlight a central role for an acute but transient CD4 decrease, as well as CD4+ T-cell activation, as independent factors for prediction of set-point levels of virus replication.
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| 17. |
- Koopman, G, et al.
(author)
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Immune-response profiles induced by human immunodeficiency virus type 1 vaccine DNA, protein or mixed-modality immunization: increased protection from pathogenic simian-human immunodeficiency virus viraemia with protein/DNA combination
- 2008
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In: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 89:Pt 2, s. 540-553
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Journal article (peer-reviewed)abstract
- Current data suggest that prophylactic human immunodeficiency virus type 1 (HIV) vaccines will be most efficacious if they elicit a combination of adaptive humoral and T-cell responses. Here, we explored the use of different vaccine strategies in heterologous prime–boost regimes and evaluated the breadth and nature of immune responses in rhesus monkeys induced by epidermally delivered plasmid DNA or recombinant HIV proteins formulated in the AS02A adjuvant system. These immunogens were administered alone or as either prime or boost in mixed-modality regimes. DNA immunization alone induced cell-mediated immune (CMI) responses, with a strong bias towards Th1-type cytokines, and no detectable antibodies to the vaccine antigens. Whenever adjuvanted protein was used as a vaccine, either alone or in a regime combined with DNA, high-titre antibody responses to all vaccine antigens were detected in addition to strong Th1- and Th2-type CMI responses. As the vaccine antigens included HIV-1 Env, Nef and Tat, as well as simian immunodeficiency virus (SIV)mac239 Nef, the animals were subsequently exposed to a heterologous, pathogenic simian–human immunodeficiency virus (SHIV)89.6p challenge. Protection against sustained high virus load was observed to some degree in all vaccinated groups. Suppression of virus replication to levels below detection was observed most frequently in the group immunized with protein followed by DNA immunization, and similarly in the group immunized with DNA alone. Interestingly, control of virus replication was associated with increased SIV Nef- and Gag-specific gamma interferon responses observed immediately following challenge.
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| 18. |
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| 19. |
- Monte, L., et al.
(author)
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The EVANET_HYDRA network: Introduction
- 2005
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In: Evaluation and nertwork of EC-decision support systems in the field of hydrological dispersion models and of aquatic radioecological research. - : ENEA, Rome. ; , s. 15-20
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Book chapter (peer-reviewed)
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| 20. |
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