Karolinska Institutet

About: Karolinska Institutet is a education organization based out in Stockholm, Sweden. It is known for research contribution in the topics: Population & Cancer. The organization has 46212 authors who have published 121142 publications receiving 6008130 citations.

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Ascending Monoamine Neurons to the Telencephalon and Diencephalon

Abstract: By means of sensitive and specific methods for histochemical and biochemical determination of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) we have succeeded in demonstrating and mapping out a number of ascending monoamine neuron systems from the lower brain stem by studying the anterograde and retrograde changes that occur in these neurons after various types of brain lesions. In this way it has been possible to discover: 1) a large, uncrossed nigro-neostriatal DA neuron system; 2) a DA neuron system, arising from cell-bodies in the mesen-cephalon, ascending uncrossed in the medial forebrain bundle close to the nigro-neostriatal DA fibres, and innervating e.g. the tuberculum olfactorium and nuc. accumbens; 3) ascending NA neuron systems with cell-bodies situated mainly in the medulla oblongata and pons (locus coeruleus, formatio reticularis), and axons running uncrossed mainly in the medial forebrain bundle, innervating e.g. the limbic forebrain structures, the neocortex and the hypothalamus; 4) ascending 5-HT' neurons with cell-bodies situated mainly in the raphe nuclei of the mesencephalon (nuc. raphe dorsalis, nuc. raphe medianus), and axons running uncrossed mainly in the medial forebrain bundle, innervating e.g. the limbic forebrain structures and the hypothalamus. The effects observed on the amine levels of the neurons represent intraneuronal and not transsynaptic changes.

Applied bioinformatics for the identification of regulatory elements

Abstract: The compilation of multiple metazoan genome sequences and the deluge of large-scale expression data have combined to motivate the maturation of bioinformatics methods for the analysis of sequences that regulate gene transcription. Historically, these bioinformatics methods have been plagued by poor predictive specificity, but new bioinformatics algorithms that accelerate the identification of regulatory regions are drawing disgruntled users back to their keyboards. However, these new approaches and software are not without problems. Here, we introduce the purpose and mechanisms of the leading algorithms, with a particular emphasis on metazoan sequence analysis. We identify key issues that users should take into consideration in interpreting the results and provide an online training example to help researchers who wish to test online tools before taking an independent foray into the bioinformatics of transcription regulation.

Defeating Alzheimer's disease and other dementias: a priority for European science and society

Abstract: Defeating Alzheimer's disease and other dementias : a priority for European science and society