Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS

Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer

Colon tumors from four independent mouse models and 100 human colorectal cancers all exhibited striking recapitulation of embryonic colon gene expression from embryonic days 13.5-18.5

Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes

Epidemiological studies consistently show that circulating sex hormone binding globulin (SHBG) levels are lower in type 2 diabetes patients than non-diabetic individuals, but the causal nature of this association is controversial. Genetic studies can help dissect causal directions of epidemiological associations because genotypes are much less likely to be confounded, biased or influenced by disease processes. Using this Mendelian randomization principle, we selected a common single nucleotide polymorphism (SNP) near the SHBG gene, rs1799941, that is strongly associated with SHBG levels. We used data from this SNP, or closely correlated SNPs, in 27 657 type 2 diabetes patients and 58 481 controls from 15 studies. We then used data from additional studies to estimate the difference in SHBG levels between type 2 diabetes patients and controls. The SHBG SNP rs1799941 was associated with type 2 diabetes [odds ratio (OR) 0.94, 95% CI: 0.91, 0.97; P = 2 × 10−5], with the SHBG raising allele associated with reduced risk of type 2 diabetes. This effect was very similar to that expected (OR 0.92, 95% CI: 0.88, 0.96), given the SHBG-SNP versus SHBG levels association (SHBG levels are 0.2 standard deviations higher per copy of the A allele) and the SHBG levels versus type 2 diabetes association (SHBG levels are 0.23 standard deviations lower in type 2 diabetic patients compared to controls). Results were very similar in men and women. There was no evidence that this variant is associated with diabetes-related intermediate traits, including several measures of insulin secretion and resistance. Our results, together with those from another recent genetic study, strengthen evidence that SHBG and sex hormones are involved in the aetiology of type 2 diabetes

The GAPS Programme at TNG. XXI. A GIARPS case study of known young planetary candidates: confirmation of HD 285507 b and refutation of AD Leonis b

Context. The existence of hot Jupiters is still not well understood. Two main channels are thought to be responsible for their current location: a smooth planet migration through the protoplanetary disk or the circularization of an initial highly eccentric orbit by tidal dissipation leading to a strong decrease in the semimajor axis. Different formation scenarios result in different observable effects, such as orbital parameters (obliquity and eccentricity) or frequency of planets at different stellar ages. Aims: In the context of the GAPS Young Objects project, we are carrying out a radial velocity survey with the aim of searching and characterizing young hot-Jupiter planets. Our purpose is to put constraints on evolutionary models and establish statistical properties, such as the frequency of these planets from a homogeneous sample. Methods: Since young stars are in general magnetically very active, we performed multi-band (visible and near-infrared) spectroscopy with simultaneous GIANO-B + HARPS-N (GIARPS) observing mode at TNG. This helps in dealing with stellar activity and distinguishing the nature of radial velocity variations: stellar activity will introduce a wavelength-dependent radial velocity amplitude, whereas a Keplerian signal is achromatic. As a pilot study, we present here the cases of two known hot Jupiters orbiting young stars: HD 285507 b and AD Leo b. Results: Our analysis of simultaneous high-precision GIARPS spectroscopic data confirms the Keplerian nature of the variation in the HD 285507 radial velocities and refines the orbital parameters of the hot Jupiter, obtaining an eccentricity consistent with a circular orbit. Instead, our analysis does not confirm the signal previously attributed to a planet orbiting AD Leo. This demonstrates the power of the multi-band spectroscopic technique when observing active stars. Photometry, RV, and time series are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/cat/J/A+A/638/A5 Based on observations made with the Italian Telescopio Nazionale Galileo (TNG) operated by the Fundación Galileo Galilei (FGG) of the Istituto Nazionale di Astrofisica (INAF) at the Observatorio del Roque de los Muchachos (La Palma, Canary Islands, Spain). Partly based on data obtained with the STELLA robotic telescopes in Tenerife, an AIP facility jointly operated by AIP and IAC

A Genome-Wide Association Meta-Analysis of Circulating Sex Hormone-Binding Globulin Reveals Multiple Loci Implicated in Sex Steroid Hormone Regulation

WOS:000306840400020Peer reviewe