| 1. |
|
|
| 2. |
- Antoniou, A. C., et al.
(författare)
-
Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers : Implications for risk prediction
- 2010
-
Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:23, s. 9742-9754
-
Tidskriftsartikel (refereegranskat)abstract
- The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10-11 - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.
|
|
| 3. |
- Weiner, D. J., et al.
(författare)
-
Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
- 2017
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:7
-
Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Anney, R. J. L., et al.
(författare)
-
Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia
- 2017
-
Ingår i: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) < 1.15). Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P= 9 x10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23. Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental- related genes such as EXT1, ASTN2, MACROD2, and HDAC4.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Gross, Sean M., et al.
(författare)
-
A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses
- 2022
-
Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
-
Tidskriftsartikel (refereegranskat)abstract
- The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
|
|
| 22. |
- Smoller, JW, et al.
(författare)
-
Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.
- 2013
-
Ingår i: Lancet. - 1474-547X. ; 381:9875, s. 1371-9
-
Tidskriftsartikel (refereegranskat)abstract
- Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia.
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Szatmari, Peter, et al.
(författare)
-
Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
- 2007
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
-
Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
|
|
| 34. |
|
|
| 35. |
- Ade, Peter, et al.
(författare)
-
The Simons Observatory : science goals and forecasts
- 2019
-
Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
-
Tidskriftsartikel (refereegranskat)abstract
- The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
|
|
| 36. |
- Anney, Richard, et al.
(författare)
-
A genome-wide scan for common alleles affecting risk for autism.
- 2010
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
-
Tidskriftsartikel (refereegranskat)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
|
|
| 37. |
- Anney, Richard, et al.
(författare)
-
Individual common variants exert weak effects on the risk for autism spectrum disorders.
- 2012
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92
-
Tidskriftsartikel (refereegranskat)abstract
- While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
|
|
| 38. |
|
|
| 39. |
- Bergen, AW, et al.
(författare)
-
Association of multiple DRD2 polymorphisms with anorexia nervosa
- 2005
-
Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X. ; 30:9, s. 1703-1710
-
Tidskriftsartikel (refereegranskat)
|
|
| 40. |
- Bulik, CM, et al.
(författare)
-
Selection of eating-disorder phenotypes for linkage analysis
- 2005
-
Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. - : Wiley. - 1552-4841. ; 139B:1, s. 81-87
-
Tidskriftsartikel (refereegranskat)
|
|
| 41. |
|
|
| 42. |
- Evans, A. O., et al.
(författare)
-
Magnetic properties of deformed dipole bands in Te-110,Te-112
- 2006
-
Ingår i: Physica Scripta. - 0031-8949. ; T125, s. 192-193
-
Tidskriftsartikel (refereegranskat)abstract
- A lifetime analysis using the Doppler-shift attenuation method has been performed on the Tellurium isotopes Te-110,Te-112. The experiment was performed using the Gammasphere array in conjunction with the MICROBALL charged-particle detector. Three strongly coupled bands were previously established in Te-110,Te-112 which were observed up to unusually high spins. In the current experiment, it has been possible to extract lifetime measurements using a Doppler broadened lineshape analysis on one of the Delta I = 1 band structures in Te-110. In contrast to similar Delta I = 1 structures in other nuclei in this mass region, the extracted B(M1) values did not rapidly decrease with increasing angular momentum. Instead, the strongly coupled band in Te-110 represents a deformed 1p-1h structure, rather than a weakly deformed structure showing the shears mechanism.
|
|
| 43. |
|
|
| 44. |
|
|
| 45. |
- Ideguchi, E., et al.
(författare)
-
Orbifold projection in supersymmetric QCD at N(f) ≤ N(c)
- 2000
-
Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 492:3-4, s. 369-375
-
Tidskriftsartikel (refereegranskat)abstract
- Supersymmetric orbifold projection of N = 1 SQCD with relatively small number of flavors (N(f) ≤ N(c)) is considered. The purpose is to check whether orbifolding commutes with the infrared limit. On the one hand, one considers the orbifold projection of SQCD and obtains the low-energy description of the resulting theory. On the other hand, one starts with the low-energy effective theory of the original SQCD, and only then performs orbifolding. It is shown that at finite N(c) the two low-energy theories obtained in these ways are different. However, in the case of stabilized run-away vacuum these two theories are shown to coincide in the large N(c) limit. In the case of quantum modified moduli space, topological solitons carrying baryonic charges are present in the orbifolded low-energy theory. These solitons may restore the correspondence between the two theories provided that the soliton mass tends to zero in the large N(c) limit. (C) 2000 Elsevier Science B.V.
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
- Klump, KL, et al.
(författare)
-
Personality characteristics of women before and after recovery from an eating disorder
- 2004
-
Ingår i: Psychological medicine. - : Cambridge University Press (CUP). - 0033-2917 .- 1469-8978. ; 34:8, s. 1407-1418
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Previous studies of personality characteristics in women with eating disorders primarily have focused on women who are acutely ill. This study compares personality characteristics among women who are ill with eating disorders, recovered from eating disorders, and those without eating or other Axis I disorder pathology.Method. Female participants were assessed for personality characteristics using the Temperament and Character Inventory (TCI): 122 with anorexia nervosa (AN; 77 ill, 45 recovered), 279 with bulimia nervosa (BN; 194 ill, 85 recovered), 267 with lifetime histories of both anorexia and bulimia nervosa (AN+BN; 194 ill, 73 recovered), 63 with eating disorder not otherwise specified (EDNOS; 31 ill, 32 recovered), and 507 without eating or Axis I disorder pathology.Results. Women ill with all types of eating disorders exhibited several TCI score differences from control women, particularly in the areas of novelty-seeking, harm avoidance, self-directedness, and cooperativeness. Interestingly, women recovered from eating disorders reported higher levels of harm avoidance and lower self-directedness and cooperativeness scores than did normal control women.Conclusions. Women with eating disorders in both the ill and recovered state show higher levels of harm avoidance and lower self-directedness and cooperativeness scores than normal control women. Although findings suggest that disturbances may be trait-related and contribute to the disorders' pathogenesis, additional research with more representative community controls, rather than our pre-screened, normal controls, is needed to confirm these impressions.
|
|
| 49. |
- Kraemer, Benjamin M., et al.
(författare)
-
Climate change drives widespread shifts in lake thermal habitat
- 2021
-
Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 11:6, s. 521-529
-
Tidskriftsartikel (refereegranskat)abstract
- Lake surfaces are warming worldwide, raising concerns about lake organism responses to thermal habitat changes. Species may cope with temperature increases by shifting their seasonality or their depth to track suitable thermal habitats, but these responses may be constrained by ecological interactions, life histories or limiting resources. Here we use 32 million temperature measurements from 139 lakes to quantify thermal habitat change (percentage of non-overlap) and assess how this change is exacerbated by potential habitat constraints. Long-term temperature change resulted in an average 6.2% non-overlap between thermal habitats in baseline (1978-1995) and recent (1996-2013) time periods, with non-overlap increasing to 19.4% on average when habitats were restricted by season and depth. Tropical lakes exhibited substantially higher thermal non-overlap compared with lakes at other latitudes. Lakes with high thermal habitat change coincided with those having numerous endemic species, suggesting that conservation actions should consider thermal habitat change to preserve lake biodiversity. Using measurements from 139 global lakes, the authors demonstrate how long-term thermal habitat change in lakes is exacerbated by species' seasonal and depth-related constraints. They further reveal higher change in tropical lakes, and those with high biodiversity and endemism.
|
|
| 50. |
- LaFosse, D. R., et al.
(författare)
-
Collective structures and band termination in 107Sb
- 2000
-
Ingår i: Physical Review C - Nuclear Physics. - 0556-2813. ; 62:1
-
Tidskriftsartikel (refereegranskat)abstract
- High-spin states in the near proton-dripline nucleus 107Sb have been identified, and collectivity in this nucleus has been observed for the first time in the form of two rotational bands. One of the observed rotational structures is a ΔI = 1 band, and is interpreted as based on a π(g9/2)-1 ⊗ π(g7/2d5/2)2 proton configuration. A second structure has ΔI = 2 character, and is explained as being based on a πh11/2⊗[π(g9/2)-2 ⊗ π(g7/2d5/2)2] proton configuration through comparison with cranked Nilsson-Strutinsky model calculations. The calculations predict that this band terminates at a spin of 79/2 (Latin small letter h with stroke).
|
|
