| 1. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 2. |
- Lappalainen, Tuuli, et al.
(författare)
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Transcriptome and genome sequencing uncovers functional variation in humans
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 501:7468, s. 506-511
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Tidskriftsartikel (refereegranskat)abstract
- Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of messenger RNA and microRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project-the first uniformly processed high-throughput RNA-sequencing data from multiple human populations with high-quality genome sequences. We discover extremely widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on the cellular mechanisms of regulatory and loss-of-function variation, and allows us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome.
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| 3. |
- Osorio, Ana, et al.
(författare)
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DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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| 4. |
- Bushby, Katharine, et al.
(författare)
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Ataluren treatment of patients with nonsense mutation dystrophinopathy.
- 2014
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Ingår i: Muscle & nerve. - : Wiley. - 1097-4598 .- 0148-639X. ; 50:4, s. 477-87
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Tidskriftsartikel (refereegranskat)abstract
- Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders.
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| 5. |
- Elks, Cathy E, et al.
(författare)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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Tidskriftsartikel (refereegranskat)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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| 6. |
- Trivino, Maria, et al.
(författare)
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Risk assessment for Iberian birds under global change
- 2013
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Ingår i: Biological Conservation. - : Elsevier BV. - 1873-2917 .- 0006-3207. ; 168, s. 192-200
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Tidskriftsartikel (refereegranskat)abstract
- Conservation priority areas and programs are often established without consideration of future changes in species distributions. However, global change is expected to threaten the persistence of several species while offering opportunities for range expansion to others. In this study, building on previous work, we develop and implement an approach to classify bird species according to their degree of exposure and vulnerability to future climate and land-use change, including climatically driven changes in vegetation. To examine species exposure to environmental changes, we first fitted environmental envelope models and projected then into the future under scenarios of climate, land use and vegetation change. Then, we estimated species vulnerability by taking into account traits that are expected to render species vulnerable to environmental change while considering, simultaneously, the current IUCN conservation status of species. Our results show that bird species highly (and negatively) exposed to future environmental changes are currently less threatened and possess characteristics that render them less susceptible to local extinction than species that are less exposed. Our results reinforce the need to complement studies of global change impacts on biodiversity, typically based on assessments of species exposure to changes, with additional information related to the ability of species to persist under such changes. Nevertheless, we stress that while combining different sources of information is important, it is the comparison of outcomes from these different sources of information that enables development of alternative management strategies. Depending on the source of risk (e.g., exposure to global change versus vulnerability traits to multiple stressors) alternative conservation actions might be required. (C) 2013 Elsevier Ltd. All rights reserved.
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| 7. |
- Trivino, Maria, et al.
(författare)
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The Contribution of Vegetation and Landscape Configuration for Predicting Environmental Change Impacts on Iberian Birds
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:12
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Tidskriftsartikel (refereegranskat)abstract
- Although climate is known to be one of the key factors determining animal species distributions amongst others, projections of global change impacts on their distributions often rely on bioclimatic envelope models. Vegetation structure and landscape configuration are also key determinants of distributions, but they are rarely considered in such assessments. We explore the consequences of using simulated vegetation structure and composition as well as its associated landscape configuration in models projecting global change effects on Iberian bird species distributions. Both present-day and future distributions were modelled for 168 bird species using two ensemble forecasting methods: Random Forests (RF) and Boosted Regression Trees (BRT). For each species, several models were created, differing in the predictor variables used (climate, vegetation, and landscape configuration). Discrimination ability of each model in the present-day was then tested with four commonly used evaluation methods (AUC, TSS, specificity and sensitivity). The different sets of predictor variables yielded similar spatial patterns for well-modelled species, but the future projections diverged for poorly-modelled species. Models using all predictor variables were not significantly better than models fitted with climate variables alone for ca. 50% of the cases. Moreover, models fitted with climate data were always better than models fitted with landscape configuration variables, and vegetation variables were found to correlate with bird species distributions in 26-40% of the cases with BRT, and in 1-18% of the cases with RF. We conclude that improvements from including vegetation and its landscape configuration variables in comparison with climate only variables might not always be as great as expected for future projections of Iberian bird species.
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| 8. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 9. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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