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  • NARCIS (Royal Netherlands Academy of Arts and Sciences)  (4)
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  • 1
    Language: English
    In: Biological Psychiatry, 01 April 2013, Vol.73(7), pp.667-678
    Description: Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits ( 〈1×10 ) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies. The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest = 1.05×10 ). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set ( = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, = 9.19×10 ). This 5q21 region reached genome-wide significance ( = 4.78×10 ) in the overall meta-analysis combining discovery and replication studies ( = 51,258). The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms.
    Keywords: Center for Epidemiologic Studies Depression Scale ; Charge Consortium ; Depression ; Depressive Symptoms ; Genetics ; Genome-Wide Association Study ; Meta-Analysis ; Medicine ; Biology ; Chemistry
    ISSN: 0006-3223
    E-ISSN: 1873-2402
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  • 2
    Language: English
    In: Nature (London), 01 November 2017, Vol.551
    Description: Our growing awareness of the importance and diversity of the microbial world contrasts starkly with our limited understanding of its fundamental structure. Despite remarkable advances in DNA sequence generation, a lack of standardized protocols and common analytical framework impede useful comparison between studies, hindering development of global inferences about microbial life on Earth. Here, we show that with coordinated protocols, exact microbial 16S rRNA gene sequences can be followed across scores of individual studies, revealing patterns of diversity, community structure, and life history strategy at a planetary scale. Using 27,751 crowdsourced environmental samples comprising more than 2.2 billion reads, we find sharp divides between host-associated and free-living communities. We show that the distribution of taxonomic and sequence diversity follows consistent trends across samples types and along gradients of environmental parameters, highlighting some of the global evolutionary patterns and ecological principles that underpin Earth’s microbiome. Here, this dataset provides the most complete environmental survey of our microbial world to date, and serves as a growing reference to provide immediate global context to future microbial surveys.
    Keywords: Environmental Sciences ; Microbiome ; Earth ; Global ; Basic Biological Sciences ; Sciences (General) ; Environmental Sciences ; Physics
    ISSN: 0028-0836
    E-ISSN: 1476-4687
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  • 3
    Language: English
    In: Molecular Psychiatry, 2016, Vol.21(2), pp.189-197
    Description: textabstractTo identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32 070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10 -8) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10 -9 after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10 -4). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10 -15), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10 -11) and neuron cell-cell adhesion (P-value=1.48 × 10 -13). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.
    Keywords: Single Nucleotide Polymorphisms -- Research ; Dementia -- Diagnosis ; Dementia -- Genetic Aspects ; Dementia -- Research ; Gaba -- Physiological Aspects ; Gaba -- Genetic Aspects ; Gaba -- Research;
    ISSN: 13594184
    E-ISSN: 14765578
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  • 4
    In: Ecology and Evolution, January 2017, Vol.7(1), pp.145-188
    Description: The project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems ()—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity. The collation of biodiversity datasets with broad taxonomic, biogeographic, and spatial extents is necessary to understand historical declines and to project—and hopefully avert—future declines. We describe and make freely available a database of more than 3.2 million biodiversity measurements from 94 countries representing over 47,000 species, collated from 480 existing spatial comparisons of local‐scale biodiversity exposed to different intensities and pressures relating to land use, from terrestrial sites around the world.
    Keywords: Data Sharing ; Global Biodiversity Modeling ; Global Change ; Habitat Destruction ; Land Use
    ISSN: 2045-7758
    E-ISSN: 2045-7758
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