New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

A 9000 years record of Chagas' disease (American trypanosomiasis)

Trypanosoma cruzi by molecular study of pre-Columbian mummie

Aspects of ingestion transmission of changas disease identified in mummies and their coprolites

Molecular study of Trypanosoma cruzi (T. cruzi) anciant DNA (aDNA) in the soft (nonskeletal) tissues of 283 naturally (spontaneously) mummified bodies from coastal sites located in southern Peru and northern Chile demonstrated a Chagas disease prevalence rate of about 41% over the past 9,000 years. This rate is similar to that of several endemic areas within this region prior to initiation of public health control programs. This report focuses on the presence of T. cruzi aDNA in the coprolites of some of these mummies. Review of the possible mechanisms that may explain the presence of this parasite in the coprolites indicates numerous antemortem and postmortem circumstances that conceivably could have been responsible. In given conditions, all of these may need to be considered. These considerations indicate that the presence of T. cruzi aDNA in mummy coprolites cannot categorically be considered as evidence of ingestion of the parasiteEl estudio molecular del tejido blando de 283 de cuerpos momificados en forma natural proveniente de la costa del sur de Perú y norte de Chile revela la presencia de Tripanosoma cruzi a partir de 9.000 años atrás con una prevalencia de un 41%. Este valor es parecido a áreas de estas regiones donde la enfermedad era endémica, antes que se iniciaran los programas de control de la salud. Este ensayo discute la presencia de ADNa de T. cruzi en los coprolitos de momias y revisa los posibles mecanismos de estos parásitos en los coprolitos. La presencia de T. cruzi en los coprolitos de momia no necesariamente indica que hubo una ingesta de este parásit

A 9,000-year record of Chagas' disease

Tissue specimens from 283 principally spontaneously (naturally) desiccated human mummies from coastal and low valley sites in northern Chile and southern Peru were tested with a DNA probe directed at a kinetoplast DNA segment of Trypanosoma cruzi. The time interval spanned by the eleven major cultural groups represented in the sample ranged from ≈9,000 years B.P. (7050 B.C.) to approximately the time of the Spanish conquest, ≈450 B.P. (≈1500 A.D.). Forty-one percent of the tissue extracts, amplified by the PCR reacted positively (i.e., hybridized) with the probe. Prevalence patterns demonstrated no statistically significant differences among the individual cultural groups, nor among subgroups compared on the basis of age, sex, or weight of specimen tested. These results suggest that the sylvatic (animal-infected) cycle of Chagas' disease was probably well established at the time that the earliest humans (members of the Chinchorro culture) first peopled this segment of the Andean coast and inadvertently joined the many other mammal species acting as hosts for this parasite

Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders

<p>Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.</p>