Alcohol Consumption, Beverage Preference, and Diet in Middle-Aged Men from the STANISLAS Study

The question about differences in dietary patterns associated with beer, wine, and spirits is still unresolved. We used diet data from 423 middle-aged males of the STANISLAS Study. Using adjusted values for covariates, we observed a negative significant association between increasing alcohol intakes and the consumption of milk, yogurt, and fresh/uncured cheese, sugar and confectionery, vegetables and fruits, and a significant positive relationship with cheese, meat and organs, pork-butcher's meat, and potatoes. In addition, the first dietary pattern identified by factor analysis (characterized a more prudent diet) was inversely related to alcohol intakes. Conversely, when analyzing daily consumption of specific food groups and diet patterns according to beverage preference (wine, beer, and spirits), no significant difference was observed. In conclusion, in this sample of middle-aged French males, there was a linear trend between increasing alcohol intakes and worsening of quality of diet, while no difference was observed according to beverage preference

Fouille de données biomédicales complexes : extraction de règles et de profils génétiques dans le cadre de l'étude du syndrome métabolique

5 pagesNous décrivons une étude sur la fouille de données de la cohorte STANISLAS qui met en œuvre l'extraction de motifs fréquents et de règles d'association. D'une part, nous avons extrait des connaissances utiles et nouvelles pour l'expert qui lui ont permis de générer de nouvelles hypothèses de recherche en biologie. D'autre part, ces travaux nous ont conduit à proposer les premiers éléments d'une méthodologie de fouille de règles extraites en bioinformatique. Au cœur de ces réflexions, nous soulignons le rôle majeur de l'expert dans le processus de fouille de données. Les résultats obtenus sont satisfaisants et illustrent le potentiel des méthodes symboliques de fouille de données en biologie

Exploitation des données de la cohorte STANISLAS par des techniques de fouille de données numériques et symboliques utilisées seules ou en combinaison

La cohorte STANISLAS est une population de familles d'origine française supposées saines, recrutées au Centre de Médecine Préventive de Vandoeuvre-lès-Nancy et suivies tous les cinq ans sur une période de dix ans. Les données de la cohorte, de types numérique et textuel, représentent une richesse et un volume considérables, exploitées jusque là par des méthodes statistiques classiques. Nous proposons d'étudier ces données par des techniques de fouille de données numériques et symboliques, en nous intéressant plus exactement à l'étude du syndrome métabolique dans la cohorte STANISLAS, une affection correspondant à la présence simultanée chez un individu de plusieurs facteurs de risques cardiovasculaires. Nous présentons ici nos recherches en cours sur ce domaine, qui font intervenir l'utilisation de la boîte à outils Weka et de J-Close, une implémentation en Java d'un algorithme d'extraction de motifs fréquents et de règles d'association. Ultérieurement nous projetons le couplage d'un module de classification de Weka avec J-Close

VEGF-related polymorphisms identified by GWAS and risk for major depression

La depresión es una enfermedad mental común, grave e incapacitante que afecta a millones de personas de todas las edades en todo el mundo. Varios estudios han demostrado que los factores neurotróficos / de crecimiento tienen un papel clave en la depresión y, más específicamente, el factor de crecimiento endotelial vascular (VEGF) está implicado en la patogénesis de la depresión. El propósito de este estudio fue investigar los posibles vínculos entre cuatro polimorfismos de un solo nucleótido (SNP) relacionados con VEGF, previamente identificados a través de un estudio de asociación de genoma completo (GWAS) y la depresión. Los efectos directos y las interacciones epistáticas de los cuatro SNP relacionados con VEGF (rs10738760, rs6921438, rs6993770 y rs4416670) sobre la depresión se investigaron a través de un estudio de casos y controles que incluyó a 437 personas diagnosticadas con depresión y 477 voluntarios sanos como controles. El sexo, la edad y la influencia del índice de masa corporal se analizaron adicionalmente. El SNP rs4416670 se asoció con un mayor riesgo de depresión (OR: 1.60, P: 0.010). Este resultado demuestra la existencia de relaciones entre los determinantes genéticos del VEGF y la depresión. Esta novedosa asociación revela nuevos mecanismos moleculares que sugieren el papel potencial del VEGF en el desarrollo de la depresión que podría ayudar a promover una predicción personalizada para esta enfermedad común grave.Depression is a common, severe, disabling mental disease that affects millions of people of all ages worldwide. Various studies have shown that neurotrophic/growth factors have a key role in depression and, more specifically, vascular endothelial growth factor (VEGF) is implicated in the pathogenesis of depression. The purpose of this study was to investigate the potential links between four VEGF-related single-nucleotide polymorphisms (SNPs), previously identified through a genome-wide association study (GWAS) and depression. The direct effects and epistatic interactions of the four VEGF-related SNPs (rs10738760, rs6921438, rs6993770 and rs4416670) on depression were investigated through a case–control study including 437 individuals diagnosed with depression and 477 healthy volunteers as controls. Gender, age and body mass index influence was additionally analyzed. The SNP rs4416670 was associated with increased risk for depression (OR: 1.60, P: 0.010). This result demonstrates the existence of relationships between VEGF genetic determinants and depression. This novel association reveals new molecular mechanisms suggesting the potential role of VEGF in depression development that could help to promote a personalized prediction for this severe common disease.• Région Lorraine y Fondo Social Europeo. Ayuda • Junta de Extremadura. Ayuda TE14002, para Áura Delgado Regalado • Instituto de Salud Carlos III. Programa Sara Borrell. Proyecto CD13/00348, para Fernando de Andrés SegurapeerReviewe

Genetic determinants of circulating haptoglobin concentration

Haptoglobin (Hp) is a major plasma acute-phase glycoprotein, which binds free haemoglobin to neutralize its toxicity. The HP gene exists as two copy number variants (CNV), HP1 and HP2, which differ in two ways: serum Hp level and functional differences in Hp protein products. Both mechanisms may underlie the HP CNV’s influence on susceptibility and/or outcome in several diseases. A single nucleotide polymorphism rs2000999 has also been associated with serum Hp level. In a meta-analysis of three studies from England, France and Japan, we show that rs2000999’s effect on circulating Hp level is independent from that of the HP CNV. The combined use of rs2000999 and the HP CNV can be an important genetic epidemiological tool to discriminate between the two potential mechanisms underlying differences between HP1 and HP2 alleles

EXPRESSION OF DEFA1-3 AND RELATIONS WITH RISK FACTORSOF CARDIOVASCULAR DISEASES

The infiltration of immuno-inflammatory cells is one of the earliest and durable steps that lead to atherosclerosis. These cells produce many immune components that act as a double-edged sword in this inflammatory disease. Among these components, we note antimicrobial peptides, including defenses. Defenses are natural cationic peptides of the innate immune system. In Humans, these small peptides have a large antimicrobial spectrum. In addition, they play an important role in both infectious and inflammatory diseases. Our objective was to study the relation between alpha-defenses (DEFA) 1-3 genes expression and cardiovascular risk factors. This objective was built on the hypothesis that defenses may be involved in cardiovascular pathologies, and may serve as a new generation of biomarkers. To verify this hypothesis, we treated HL-60 differentiated cells with glucose decreased alphadefenses 1, 2 and 3 gene expression levels, while insulin treatment restored its expression. These findings suggest that DEFA1-3 are involved in the complex glucose-insulin metabolic pathway. In summary, DEFA1-3 genes expression is significantly correlated with glucose. These findings we suggest that DEFA1-3 could be involved in the evolution of cardiovascular complications

4th ESPT summer school: precision medicine and personalised health

In September 2018, the European Society of Pharmacogenomics and Personalised Therapy (ESPT), with the support of the Swiss Personalized Health Network (SPHN), organized its 4th biennial summer school, entitled 'Precision Medicine and Personalised Health' (Campus Biotech, Geneva, Switzerland; www.esptsummerschool.eu/ ). The school's comprehensive and innovative educational program aimed to address the fundamentals of pharmacogenomics, the latest knowledge on established and new concepts in the field of precision medicine, as well as its advanced clinical applications in personalized health. The school consisted of 31 lectures, eight interactive workshops, visits to genome center and poster presentations, involving 40 speakers from distinguished international faculties. The meeting was a resounding success by generating informal environments between more than 80 participants from 26 different countries

A Genome-Wide Association Study Identifies rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels

Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes to aid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobin levels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases, including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acute myocardial infarction. However, a comprehensive genetic assessment of the inter-individual variability of circulating haptoglobin levels has not been conducted so far

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes