| 1. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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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.
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| 2. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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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.
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| 3. |
- Qiu, Chengxuan, et al.
(författare)
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Cerebral microbleeds and age-related macular degeneration : the AGES-Reykjavik Study
- 2012
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 33:12, s. 2935-2937
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Tidskriftsartikel (refereegranskat)abstract
- We test the hypothesis that cerebral microbleeds (CMB) and age-related macular degeneration (AMD), both linked to amyloid-beta deposition, are correlated. This study includes 4205 participants (mean age 76.2; 57.8% women) in the Age, Gene/Environment Susceptibility (AGES)Reykjavik Study (2002-2006). CMB were assessed from magnetic resonance images, and AMD was assessed using digital retinal images. Data were analyzed with multinomial logistic models controlling for major confounders. Evidence of CMB was detected in 476 persons (272 with strict lobar CMB and 204 with nonlobar CMB). AMD was detected in 1098 persons (869 with early AMD, 140 with exudative AMD, and 89 with pure geographic atrophy). Early and exudative AMD were not associated with CMB. The adjusted odds ratio of pure geographic atrophy was 1.62 (95% confidence interval 0.93-2.82, p = 0.089) for having any CMB, 1.43 (0.66-3.06, p = 0.363) for strict lobar CMB, and 1.85 (0.89-3.87, p = 0.100) for nonlobar CMB. This study provides no evidence that amyloid deposits in the brain and AMD are correlated. However, the suggestive association of geographic atrophy with CMB warrants further investigation.
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