Organic residue analysis of Egyptian votive mummies and their research potential

YesVast numbers of votive mummies were produced in Egypt during the Late Pharaonic, Ptolemaic, and Roman periods. Although millions remain in situ, many were removed and have ultimately entered museum collections around the world. There they have often languished as uncomfortable reminders of antiquarian practices with little information available to enhance their value as artefacts worthy of conservation or display. A multi-disciplinary research project, based at the University of Manchester, is currently redressing these issues. One recent aspect of this work has been the characterization of natural products employed in the mummification of votive bundles. Using gas chromatography–mass spectrometry and the well-established biomarker approach, analysis of 24 samples from 17 mummy bundles has demonstrated the presence of oils/fats, natural waxes, petroleum products, resinous exudates, and essential oils. These results confirm the range of organic materials employed in embalming and augment our understanding of the treatment of votives. In this first systematic initiative of its kind, initial findings point to possible trends in body treatment practices in relation to chronology, geography, and changes in ideology which will be investigated as the study progresses. Detailed knowledge of the substances used on individual bundles has also served to enhance their value as display items and aid in their conservation.RCB is supported by a PhD studentship from the Art and Humanities Research Council (43019R00209). L.M. and S.A.W. are supported by a Leverhulme Trust Research Project Award (RPG-2013-143)

Mendelian randomization evaluation of causal effects of fibrinogen on incident coronary heart disease

BackgroundFibrinogen is an essential hemostatic factor and cardiovascular disease risk factor. Early attempts at evaluating the causal effect of fibrinogen on coronary heart disease (CHD) and myocardial infraction (MI) using Mendelian randomization (MR) used single variant approaches, and did not take advantage of recent genome-wide association studies (GWAS) or multi-variant, pleiotropy robust MR methodologies.Methods and findingsWe evaluated evidence for a causal effect of fibrinogen on both CHD and MI using MR. We used both an allele score approach and pleiotropy robust MR models. The allele score was composed of 38 fibrinogen-associated variants from recent GWAS. Initial analyses using the allele score used a meta-analysis of 11 European-ancestry prospective cohorts, free of CHD and MI at baseline, to examine incidence CHD and MI. We also applied 2 sample MR methods with data from a prevalent CHD and MI GWAS. Results are given in terms of the hazard ratio (HR) or odds ratio (OR), depending on the study design, and associated 95% confidence interval (CI).In single variant analyses no causal effect of fibrinogen on CHD or MI was observed. In multi-variant analyses using incidence CHD cases and the allele score approach, the estimated causal effect (HR) of a 1 g/L higher fibrinogen concentration was 1.62 (CI = 1.12, 2.36) when using incident cases and the allele score approach. In 2 sample MR analyses that accounted for pleiotropy, the causal estimate (OR) was reduced to 1.18 (CI = 0.98, 1.42) and 1.09 (CI = 0.89, 1.33) in the 2 most precise (smallest CI) models, out of 4 models evaluated. In the 2 sample MR analyses for MI, there was only very weak evidence of a causal effect in only 1 out of 4 models.ConclusionsA small causal effect of fibrinogen on CHD is observed using multi-variant MR approaches which account for pleiotropy, but not single variant MR approaches. Taken together, results indicate that even with large sample sizes and multi-variant approaches MR analyses still cannot exclude the null when estimating the causal effect of fibrinogen on CHD, but that any potential causal effect is likely to be much smaller than observed in epidemiological studies.Cardiolog

Genome-Wide Association Study for Circulating Tissue Plasminogen Activator Levels and Functional Follow-Up Implicates Endothelial STXBP5 and STX2

Cardiolog

Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.

Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10 <sup>-16</sup> , n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity