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

Evolución nutricional de niños y niñas menores de 5 años usuarios de un Programa Alimentario Nutricional Integral en Paraguay

Introducción: La desnutrición es un desafío pendiente que influye nocivamente en el desarrollo de los niños/as y de una nación.Objetivo: Evaluar la evolución del estado nutricional de niños/as <5 años ingresados a un programa alimentario durante el año 2012. Materiales y Métodos:Estudio longitudinal (cohorte), descriptivo, analítico de beneficiarios del Programa Alimentario Nutricional Integral (PANI) en el 2012.Variables sociodemográficas fueron consideradas, el diagnóstico nutricional según criterios OMS según puntaje zPeso/Edad (zP/E), Índice de Masa Corporal/Edad (zIMC/E), Talla/Edad (zT/E). Resultados: Fueron procesados datos de 4946 niños/as <5años. Edad media 17,5m (0,03-59 m), 50,3% varones; 51,4% del área rural. Al ingreso, tuvieron media zP/E-1,71±0,7DE, zIMC/Edad -1,31±1,12DE y zT/E -1,34±1,30 DE. El zP/E en controles sucesivos aumentó a -0,36 DE en el 12vo. control, el zIMC/E a 0,26DE,zT/E a -0,91 de manera significativa (ANOVA p<0,0001). 22,6% presentaban Desnutrición Global-DG y 77,4% de riesgo de desnutrir al ingreso, estas prevalencias fueron de 3,4% y 21% respectivamente con 75,6% de niños/as sin desnutrición al último control ((2,p<0,0001). 21,9% tuvieron desnutrición por IMC, y 38,5%% de riesgo de desnutrir, estas prevalencias fueron de 3,1% y 10,7% al 12vo. control. Del 26% de Desnutrición Crónica-DC, se pasó a 16% al final de la intervención. Conclusiones: La desnutrición infantil disminuye significativamente con el apoyo de un programa alimentario.

Transcription factor 4 (TCF4) and schizophrenia: integrating the animal and the human perspective

Schizophrenia is a genetically complex disease considered to have a neurodevelopmental pathogenesis and defined by a broad spectrum of positive and negative symptoms as well as cognitive deficits. Recently, large genome-wide association studies have identified common alleles slightly increasing the risk for schizophrenia. Among the few schizophrenia-risk genes that have been consistently replicated is the basic Helix-Loop-Helix (bHLH) transcription factor 4 (TCF4). Haploinsufficiency of the TCF4 (formatting follows IUPAC nomenclature: TCF4 protein/protein function, Tcf4 rodent gene cDNA mRNA, TCF4 human gene cDNA mRNA) gene causes the Pitt-Hopkins syndrome-a neurodevelopmental disease characterized by severe mental retardation. Accordingly, Tcf4 null-mutant mice display developmental brain defects. TCF4-associated risk alleles are located in putative coding and non-coding regions of the gene. Hence, subtle changes at the level of gene expression might be relevant for the etiopathology of schizophrenia. Behavioural phenotypes obtained with a mouse model of slightly increased gene dosage and electrophysiological investigations with human risk-allele carriers revealed an overlapping spectrum of schizophrenia-relevant endophenotypes. Most prominently, early information processing and higher cognitive functions appear to be associated with TCF4 risk genotypes. Moreover, a recent human study unravelled gene × environment interactions between TCF4 risk alleles and smoking behaviour that were specifically associated with disrupted early information processing. Taken together, TCF4 is considered as an integrator ('hub') of several bHLH networks controlling critical steps of various developmental, and, possibly, plasticity-related transcriptional programs in the CNS and changes of TCF4 expression also appear to affect brain networks important for information processing. Consequently, these findings support the neurodevelopmental hypothesis of schizophrenia and provide a basis for identifying the underlying molecular mechanisms