| 61. |
- Thompson, Paul M., et al.
(författare)
-
The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
-
Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 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.
|
|
| 62. |
- Tragante, Vinicius, et al.
(författare)
-
Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.
- 2014
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:3, s. 349-360
-
Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
|
|
| 63. |
|
|
| 64. |
- Wang, Li-San, et al.
(författare)
-
Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
-
Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
|
|
| 65. |
- Watson, Hunna J., et al.
(författare)
-
Common Genetic Variation and Age of Onset of Anorexia Nervosa
- 2022
-
Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
|
|
| 66. |
- Went, Molly, et al.
(författare)
-
Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology
- 2018
-
Ingår i: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- The clustering of different types of B-cell malignancies in families raises the possibility of shared aetiology. To examine this, we performed cross-trait linkage disequilibrium (LD)-score regression of multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) genome-wide association study (GWAS) data sets, totalling 11,734 cases and 29,468 controls. A significant genetic correlation between these two B-cell malignancies was shown (Rg = 0.4, P = 0.0046). Furthermore, four of the 45 known CLL risk loci were shown to associate with MM risk and five of the 23 known MM risk loci associate with CLL risk. By integrating eQTL, Hi-C and ChIP-seq data, we show that these pleiotropic risk loci are enriched for B-cell regulatory elements and implicate B-cell developmental genes. These data identify shared biological pathways influencing the development of CLL and, MM and further our understanding of the aetiological basis of these B-cell malignancies.
|
|
| 67. |
- Zhou, XP, et al.
(författare)
-
Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
|
|
| 68. |
- Aartsen, M. G., et al.
(författare)
-
Observation of Cosmic-Ray Anisotropy with the Icetop Air Shower Array
- 2013
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 765:1, s. 55-
-
Tidskriftsartikel (refereegranskat)abstract
- We report on the observation of anisotropy in the arrival direction distribution of cosmic rays at PeV energies. The analysis is based on data taken between 2009 and 2012 with the IceTop air shower array at the south pole. IceTop, an integral part of the IceCube detector, is sensitive to cosmic rays between 100 TeV and 1 EeV. With the current size of the IceTop data set, searches for anisotropy at the 10(-3) level can, for the first time, be extended to PeV energies. We divide the data set into two parts with median energies of 400 TeV and 2 PeV, respectively. In the low energy band, we observe a strong deficit with an angular size of about 30 degrees and an amplitude of (-1.58 +/- 0.46(stat) +/- 0.52(sys)) x 10(-3) at a location consistent with previous observations of cosmic rays with the IceCube neutrino detector. The study of the high energy band shows that the anisotropy persists to PeV energies and increases in amplitude to (-3.11 +/- 0.38(stat) +/- 0.96(sys)) x 10(-3).
|
|
| 69. |
- Aartsen, M. G., et al.
(författare)
-
Search for Galactic PeV gamma rays with the IceCube Neutrino Observatory
- 2013
-
Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 87:6, s. 062002-
-
Tidskriftsartikel (refereegranskat)abstract
- Gamma-ray induced air showers are notable for their lack of muons, compared to hadronic showers. Hence, air shower arrays with large underground muon detectors can select a sample greatly enriched in photon showers by rejecting showers containing muons. IceCube is sensitive to muons with energies above similar to 500 GeV at the surface, which provides an efficient veto system for hadronic air showers with energies above 1 PeV. One year of data from the 40-string IceCube configuration was used to perform a search for point sources and a Galactic diffuse signal. No sources were found, resulting in a 90% C.L. upper limit on the ratio of gamma rays to cosmic rays of 1.2 x 10(-3) for the flux coming from the Galactic plane region (-80 degrees less than or similar to l less than or similar to -30 degrees; -10 degrees less than or similar to b less than or similar to 5 degrees) in the energy range 1.2-6.0 PeV. In the same energy range, point source fluxes with E-2 spectra have been excluded at a level of (E/TeV)(2)d Phi/dE similar to 10(-12)-10(-11) cm(-2) s(-1) TeV-1 depending on source declination. The complete IceCube detector will have a better sensitivity (due to the larger detector size), improved reconstruction, and vetoing techniques. Preliminary data from the nearly final IceCube detector configuration have been used to estimate the 5-yr sensitivity of the full detector. It is found to be more than an order of magnitude better, allowing the search for PeV extensions of known TeV gamma-ray emitters.
|
|
| 70. |
- Abbasi, R., et al.
(författare)
-
All-particle cosmic ray energy spectrum measured with 26 IceTop stations
- 2013
-
Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 44, s. 40-58
-
Tidskriftsartikel (refereegranskat)abstract
- We report on a measurement of the cosmic ray energy spectrum with the IceTop air shower array, the surface component of the IceCube Neutrino Observatory at the South Pole. The data used in this analysis were taken between June and October, 2007, with 26 surface stations operational at that time, corresponding to about one third of the final array. The fiducial area used in this analysis was 0.122 km(2). The analysis investigated the energy spectrum from 1 to 100 PeV measured for three different zenith angle ranges between 0 degrees and 46 degrees. Because of the isotropy of cosmic rays in this energy range the spectra from all zenith angle intervals have to agree. The cosmic-ray energy spectrum was determined under different assumptions on the primary mass composition. Good agreement of spectra in the three zenith angle ranges was found for the assumption of pure proton and a simple two-component model. For zenith angles theta < 30 degrees, where the mass dependence is smallest, the knee in the cosmic ray energy spectrum was observed at about 4 PeV, with a spectral index above the knee of about -3.1. Moreover, an indication of a flattening of the spectrum above 22 PeV was observed.
|
|
