SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Bertram Lars) "

Sökning: WFRF:(Bertram Lars)

  • Resultat 1-10 av 53
  • [1]23456Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Hibar, Derrek P., et al. (författare)
  • Common genetic variants influence human subcortical brain structures
  • 2015
  • Ingår i: Nature. - 0028-0836. ; 520:7546, s. 224-U216
  • Tidskriftsartikel (refereegranskat)abstract
    • The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume(5) and intracranial volume(6). These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 X 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
  •  
2.
  • Nikpay, Majid, et al. (författare)
  • A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
  • 2015
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 47:10, s. 1121-1130
  • Tidskriftsartikel (refereegranskat)abstract
    • Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
  •  
3.
  • Thompson, P. M., et al. (författare)
  • The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
  • 2014
  • Ingår i: BRAIN IMAGING BEHAV. - 1931-7557. ; 8:2, s. 153-182
  • 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.
  •  
4.
  • Adams, Hieab H. H., et al. (författare)
  • Novel genetic loci underlying human intracranial volume identified through genome-wide association
  • 2016
  • Ingår i: Nature Neuroscience. - 1097-6256 .- 1546-1726. ; 19:12, s. 1569-1582
  • Tidskriftsartikel (refereegranskat)abstract
    • Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
  •  
5.
  • Bellander, Martin, et al. (författare)
  • Lower baseline performance but greater plasticity of working memory for carriers of the val allele of the comt val158met polymorphism
  • 2015
  • Ingår i: Neuropsychology. - 0894-4105. ; 29:2, s. 247-254
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Little is known about genetic contributions to individual differences in cognitive plasticity. Given that the neurotransmitter dopamine is critical for cognition and associated with cognitive plasticity, we investigated the effects of 3 polymorphisms of dopamine-related genes (LMX1A, DRD2, COMT) on baseline performance and plasticity of working memory (WM), perceptual speed, and reasoning. Method: One hundred one younger and 103 older adults underwent approximately 100 days of cognitive training, and extensive testing before and after training. We analyzed the baseline and posttest data using latent change score models. Results: For working memory, carriers of the val allele of the COMT polymorphism had lower baseline performance and larger performance gains from training than carriers of the met allele. There was no significant effect of the other genes or on other cognitive domains. Conclusions: We relate this result to available evidence indicating that met carriers perform better than val carriers in WM tasks taxing maintenance, whereas val carriers perform better at updating tasks. We suggest that val carriers may show larger training gains because updating operations carry greater potential for plasticity than maintenance operations.
  •  
6.
  •  
7.
  • Davies, Gail, et al. (författare)
  • Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
  • 2018
  • Ingår i: Nature Communications. - Nature Publishing Group. - 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
8.
  • Ghisletta, Paolo, et al. (författare)
  • The Val/Met Polymorphism of the Brain-Derived Neurotrophic Factor (BDNF) Gene Predicts Decline in Perceptual Speed in Older Adults
  • 2014
  • Ingår i: Psychology and Aging. - 0882-7974. ; 29:2, s. 384-392
  • Tidskriftsartikel (refereegranskat)abstract
    • The brain-derived neurotrophic factor (BDNF) promotes activity-dependent synaptic plasticity, and contributes to learning and memory. We investigated whether a common Val66Met missense polymorphism (rs6265) of the BDNF gene is associated with individual differences in cognitive decline (marked by perceptual speed) in old age. A total of 376 participants of the Berlin Aging Study, with a mean age of 83.9 years at first occasion, were assessed longitudinally up to 11 times across more than 13 years on the Digit-Letter task. Met carriers (n = 123, 34%) showed steeper linear decline than Val homozygotes (n = 239, 66%); the corresponding contrast explained 2.20% of the variance in change in the entire sample, and 3.41% after excluding individuals at risk for dementia. These effects were not moderated by sex or socioeconomic status. Results are consistent with the hypothesis that normal aging magnifies the effects of common genetic variation on cognitive functioning.
  •  
9.
  • Giedraitis, Vilmantas, et al. (författare)
  • CALHM1 P86L polymorphism does not alter amyloid-beta or tau in cerebrospinal fluid
  • 2010
  • Ingår i: Neuroscience Letters. - 0304-3940 .- 1872-7972. ; 469:2, s. 265-267
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, the P86L alteration in CALHM1 (calcium homeostasis modulator-1) was reported to be associated with Alzheimer's disease (AD). Moreover, the risk allele increased amyloid-beta (A beta) levels in conditioned media from cultured cells. Therefore, we hypothesized that CALHM1 P86L may modulate A beta or tau levels in cerebrospinal fluid (CSF). Nearly 200 individuals with AD or other cognitive disorders were included for CSF analysis and CALHM1 genotyping. No significant differences in CSF levels of A beta 42, tau or phospho-tau were found across the various CALHM1 genotypes. In conclusion, we found no evidence that CALHM1 P86L is associated with altered CSF levels of the investigated AD biomarkers.
  •  
10.
  • Hibar, Derrek P., et al. (författare)
  • Novel genetic loci associated with hippocampal volume
  • 2017
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 53
  • [1]23456Nästa
Åtkomst
fritt online (12)
Typ av publikation
tidskriftsartikel (53)
Typ av innehåll
refereegranskat (51)
övrigt vetenskapligt (2)
Författare/redaktör
Bertram, Lars, (35)
Hofman, Albert, (12)
Liu, Tian, (12)
Gudnason, Vilmundur, (11)
Lovestone, Simon, (11)
Uitterlinden, Andre ... (11)
visa fler...
Van Duijn, Cornelia ... (11)
Lindenberger, Ulman (11)
Teumer, Alexander, (10)
Homuth, Georg, (10)
Montgomery, Grant W. ... (10)
Martin, Nicholas G., (10)
Amin, Najaf, (9)
Smith, Albert V., (9)
Boomsma, Dorret I., (9)
Deary, Ian J., (9)
Harris, Tamara B. (9)
Tsolaki, Magda (9)
Bennett, David A., (8)
Schmidt, Reinhold, (8)
Voelzke, Henry, (8)
Schmidt, Helena, (8)
Medland, Sarah E., (8)
Scheltens, Philip, (8)
Engelborghs, Sebasti ... (8)
Lind, Lars, (7)
Vandenberghe, Rik, (7)
Seshadri, Sudha, (7)
Hofer, Edith, (7)
Liewald, David C. M. ... (7)
De Jager, Philip L., (7)
Ford, Ian, (7)
Hottenga, Jouke-Jan, (7)
Psaty, Bruce M., (7)
Rotter, Jerome I., (7)
Launer, Lenore J., (7)
Wareham, Nicholas J. (7)
Salomaa, Veikko (7)
Bäckman, Lars, (7)
Gieger, Christian (7)
Martínez-Lage, Pablo (7)
Lleó, Alberto (7)
Hayward, Caroline (7)
Eriksson, Johan G. (7)
Rudan, Igor (7)
Wilson, James F. (7)
Soininen, Hilkka, (7)
Lahti, Jari, (7)
Frölich, Lutz (7)
Sleegers, Kristel (7)
visa färre...
Lärosäte
Karolinska Institutet (28)
Uppsala universitet (18)
Göteborgs universitet (17)
Umeå universitet (14)
Stockholms universitet (11)
Lunds universitet (6)
visa fler...
Örebro universitet (5)
Linköpings universitet (5)
Kungliga Tekniska Högskolan (1)
Högskolan i Jönköping (1)
visa färre...
Språk
Engelska (51)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (50)
Samhällsvetenskap (8)
Naturvetenskap (6)
Teknik (1)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy