| 1. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 2. |
- McBrien, Owen R., et al.
(författare)
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SN2018kzr : A Rapidly Declining Transient from the Destruction of a White Dwarf
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 885:1
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Tidskriftsartikel (refereegranskat)abstract
- We present SN2018kzr, the fastest declining supernova-like transient, second only to the kilonova, AT2017gfo. SN2018kzr is characterized by a peak magnitude of M-r & xfffd;=& xfffd;?17.98, a peak bolometric luminosity of ?1.4 & xfffd;& x5e0;10(43) erg s(?1), and a rapid decline rate of 0.48 & xfffd;& xfffd;0.03 mag day(?1) in the r band. The bolometric luminosity evolves too quickly to be explained by pure Ni-56 heating, necessitating the inclusion of an alternative powering source. Incorporating the spin-down of a magnetized neutron star adequately describes the lightcurve and we estimate a small ejecta mass of M-ej & xfffd;=& xfffd;0.10 & xfffd;& xfffd;0.05 M. Our spectral modeling suggests the ejecta is composed of intermediate mass elements including O, Si, and Mg and trace amounts of Fe-peak elements, which disfavors a binary neutron star merger. We discuss three explosion scenarios for SN2018kzr, given the low ejecta mass, intermediate mass element composition, and high likelihood of additional powering?the core collapse of an ultra-stripped progenitor, the accretion induced collapse (AIC) of a white dwarf, and the merger of a white dwarf and neutron star. The requirement for an alternative input energy source favors either the AIC with magnetar powering or a white dwarf?neutron star merger with energy from disk wind shocks.
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| 3. |
- Cardona, Alexia, et al.
(författare)
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Epigenome-wide association study of incident type 2 diabetes in a British population : EPIC-Norfolk study
- 2019
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 68:12, s. 2315-2326
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic changes may contribute substantially to risks of diseases of aging. Previous studies reported seven methylation variable positions (MVPs) robustly associated with incident type 2 diabetes mellitus (T2DM). However, their causal roles in T2DM are unclear. In an incident T2DM case-cohort study nested within the populationbased European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort, we used whole blood DNA collected at baseline, up to 11 years before T2DM onset, to investigate the role of methylation in the etiology of T2DM. We identified 15 novel MVPs with robust associations with incident T2DM and robustly confirmed three MVPs identified previously (near to TXNIP, ABCG1, and SREBF1). All 18 MVPs showed directionally consistent associations with incident and prevalent T2DM in independent studies. Further conditional analyses suggested that the identified epigenetic signals appear related to T2DM via glucose and obesityrelated pathways acting before the collection of baseline samples.We integrated genome-wide genetic data to identify methylation-associated quantitative trait loci robustly associated with 16 of the 18 MVPs and found one MVP, cg00574958 at CPT1A, with a possible direct causal role in T2DM. None of the implicated genes were previously highlighted by genetic association studies, suggesting that DNA methylation studies may reveal novel biological mechanisms involved in tissue responses to glycemia.
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