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- Gaulton, Kyle J, et al.
(author)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Journal article (peer-reviewed)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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- Tobin, John J., et al.
(author)
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The VLA/ALMA Nascent Disk and Multiplicity (VANDAM) Survey of Orion Protostars. I. Identifying and Characterizing the Protostellar Content of the OMC-2 FIR4 and OMC-2 FIR3 Regions
- 2019
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In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 886:1
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Journal article (peer-reviewed)abstract
- We present Atacama Large Millimeter/submillimeter Array (0.87 mm) and Very Large Array (9 mm) observations toward OMC-2 FIR4 and OMC-2 FIR3 within the Orion integral-shaped filament, thought to be two of the nearest regions of intermediate-mass star formation. We characterize the continuum sources within these regions on ?40 au (01) scales and associated molecular line emission at a factor of ?30 better resolution than previous observations at similar wavelengths. We identify six compact continuum sources within OMC-2 FIR4, four in OMC-2 FIR3, and one additional source just outside OMC-2 FIR4. This continuum emission is tracing the inner envelope and/or disk emission on less than 100 au scales. HOPS-108 is the only protostar in OMC-2 FIR4 that exhibits emission from high-excitation transitions of complex organic molecules (e.g., methanol and other lines) coincident with the continuum emission. HOPS-370 in OMC-2 FIR3, with L;?;360 L, also exhibits emission from high-excitation methanol and other lines. The methanol emission toward these two protostars is indicative of temperatures high enough to thermally evaporate it from icy dust grains; overall, these protostars have characteristics similar to hot corinos. We do not identify a clear outflow from HOPS-108 in (CO)-C-12, but we find evidence of interaction between the outflow/jet from HOPS-370 and the OMC-2 FIR4 region. A multitude of observational constraints indicate that HOPS-108 is likely a low- to intermediate-mass protostar in its main mass accretion phase and is the most luminous protostar in OMC-2 FIR4. The high-resolution data presented here are essential for disentangling the embedded protostars from their surrounding dusty environments and characterizing them.
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