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1.	Satizabal, Claudia L., et al. (författare) Genetic architecture of subcortical brain structures in 38,851 individuals 2019 Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624- Tidskriftsartikel (refereegranskat)abstract Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
2.	Wuttke, Matthias, et al. (författare) A catalog of genetic loci associated with kidney function from analyses of a million individuals 2019 Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972 Tidskriftsartikel (refereegranskat)abstract Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
3.	Kehoe, Laura, et al. (författare) Make EU trade with Brazil sustainable 2019 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341- Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
4.	Shrine, Nick, et al. (författare) New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries 2019 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 481-493 Tidskriftsartikel (refereegranskat)abstract Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.

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Typ av publikation: tidskriftsartikel (4)

Typ av innehåll: refereegranskat (3); övrigt vetenskapligt/konstnärligt (1)

Författare/redaktör: Lind, Lars (2); Raitakari, Olli T (2); Loeffler, Markus (2); Rudan, Igor (2); Franke, Barbara (1); Gyllensten, Ulf B. (1); visa fler...; Ärnlöv, Johan, 1970- (1); Wareham, Nick (1); Westman, Eric (1); Rothhaupt, Karl-Otto (1); Tsolaki, Magda (1); Ching, Christopher R ... (1); Agartz, Ingrid (1); Brouwer, Rachel M (1); Melle, Ingrid (1); Westlye, Lars T (1); Thompson, Paul M (1); Andreassen, Ole A (1); Salomaa, Veikko (1); Perola, Markus (1); Weigend, Maximilian (1); Olafsson, Isleifur (1); Imboden, Medea (1); Probst-Hensch, Nicol ... (1); Gulsvik, Amund (1); Farrell, Katharine N ... (1); Melander, Olle (1); Hansell, Anna L (1); Brenner, Hermann (1); Ouwehand, Willem H. (1); Soranzo, Nicole (1); Andersson, Micael (1); Axelsson, Tomas (1); Campbell, Harry (1); Strachan, David P (1); Islar, Mine (1); Krause, Torsten (1); Uddling, Johan, 1972 (1); Freedman, Barry I. (1); Langefeld, Carl D. (1); Alexanderson, Helena (1); Schneider, Christoph (1); Battiston, Roberto (1); Jonas, Jost B. (1); Marz, Winfried (1); van der Wee, Nic J. ... (1); Lukic, Marko (1); Pereira, Laura (1); Riggi, Laura (1); Cattaneo, Claudio (1); visa färre...

Lärosäte: Uppsala universitet (3); Lunds universitet (2); Karolinska Institutet (2); Umeå universitet (1); Kungliga Tekniska Högskolan (1); Mittuniversitetet (1); visa fler...; Chalmers tekniska högskola (1); Högskolan Dalarna (1); Sveriges Lantbruksuniversitet (1); visa färre...

Språk: Engelska (4)

Forskningsämne (UKÄ/SCB): Medicin och hälsovetenskap (3); Naturvetenskap (1); Teknik (1); Samhällsvetenskap (1)

År: 2019 (4)Ta bort avgränsningen

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