| 1. |
- Lawrenson, Kate, et al.
(author)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 2. |
- Jacobson, H. R., et al.
(author)
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The Gaia-ESO Survey : Probes of the inner disk abundance gradient
- 2016
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 591
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Journal article (peer-reviewed)abstract
- Context. The nature of the metallicity gradient inside the solar circle (R-GC < 8 kpc) is poorly understood, but studies of Cepheids and a small sample of open clusters suggest that it steepens in the inner disk. Aims. We investigate the metallicity gradient of the inner disk using a sample of inner disk open clusters that is three times larger than has previously been studied in the literature to better characterize the gradient in this part of the disk. Methods. We used the Gaia-ESO Survey (GES) [Fe/H] values and stellar parameters for stars in 12 open clusters in the inner disk from GES-UVES data. Cluster mean [Fe/H] values were determined based on a membership analysis for each cluster. Where necessary, distances and ages to clusters were determined via comparison to theoretical isochrones. Results. The GES open clusters exhibit a radial metallicity gradient of -0.10 +/- 0.02 dex kpc(-1), consistent with the gradient measured by other literature studies of field red giant stars and open clusters in the range R-GC similar to 6-12 kpc. We also measure a trend of increasing [Fe/H] with increasing cluster age, as has also been found in the literature. Conclusions. We find no evidence for a steepening of the inner disk metallicity gradient inside the solar circle as earlier studies indicated. The age-metallicity relation shown by the clusters is consistent with that predicted by chemical evolution models that include the effects of radial migration, but a more detailed comparison between cluster observations and models would be premature.
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| 3. |
- Magrini, L., et al.
(author)
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The Gaia-ESO Survey: Insights into the inner-disc evolution from open clusters
- 2015
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In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 580
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Journal article (peer-reviewed)abstract
- Context. The inner disc, which links the thin disc with the bulge, has been somewhat neglected in the past because of the intrinsic difficulties in its study, among which crowding and high extinction. Open clusters located in the inner disc are among the best tracers of its chemistry at different ages and distances. Aims. We analyse the chemical patterns of four open clusters located within 7 kpc of the Galactic centre and of field stars to infer the properties of the inner disc with the Gaia-ESO survey idr2/3 data release. Methods. We derive the parameters of the newly observed cluster, Berkeley 81, finding an age of about 1 Gyr and a Galactocentric distance of similar to 5.4 kpc. We construct the chemical patterns of clusters and we compare them with those of field stars in the solar neighbourhood and in the inner-disc samples. Results. Comparing the three populations we observe that inner-disc clusters and field stars are both, on average, enhanced in [O/Fe], [Mg/Fe], and [Si/Fe]. Using the idr2/3 results of M67, we estimate the non-local thermodynamic equilibrium (NLTE) effect on the abundances of Mg and Si in giant stars. After empirically correcting for NLTE effects, we note that NGC 6705 and Be 81 still have a high [alpha/Fe]. Conclusions. The location of the four open clusters and of the field population reveals that the evolution of the metallicity [Fe/H] and of [alpha/Fe] can be explained within the framework of a simple chemical evolution model: both [Fe/H] and [alpha/Fe] of Trumpler 20 and of NGC 4815 are in agreement with expectations from a simple chemical evolution model. On the other hand, NGC 6705, and to a lesser degree Berkeley 81, have higher [alpha/Fe] than expected for their ages, location in the disc, and metallicity. These differences might originate from local enrichment processes as explained in the inhomogeneous evolution framework.
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