Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

FTO genotype is associated with phenotypic variability of body mass index.

There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ∼170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ∼0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI, possibly mediated by DNA methylation. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.

Estructura factorial de la versión reducida del 'Eysenck Personality Profiler'

El objetivo de este trabajo es analizar la estructura factorial de la versión reducida del Eysenck Personality Profiler (EPP-SF), un cuestionario recientemente elaborado por Eysenck, Wilson y Jackson (1996) que permite la evaluación de los rasgos primarios más importantes que constituyen cada una de las tres dimensiones básicas de personalidad. Los resultados derivados de la aplicación de la técnica de análisis factorial y escalamiento multidimensional a las puntuaciones del EPP-SF de una muestra española de 946 sujetos replican los datos obtenidos en la muestra inglesa. La estructura factorial de la escala perfila claramente una composición tripartita y evidencia un aceptable grado de homogeneidad entre los rasgos primarios que constituyen cada uno de los tres tipos básicos de personalidad. Si bien, el rasgo primario de impulsividad sigue presentado saturaciones importantes en más de una dimensión. Este resultado es interpretado en los términos aducidos por el propio Eysenck, y otros autores, sobre la naturaleza multifactorial de este atributo de personalidad. Hecho que viene a constatar la necesidad de realizar estudios centrados en el análisis de la supuesta unidimensionalidad de las escalas que constituyen el EPP-SF.

Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.

Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant. Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P < 0.0001 and -0.011 pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.

Europeans and Biotechnology in 2010. Winds of change?

George Gaskell and colleagues designed, analysed and interpreted the Eurobarometer 73.1 on the Life Sciences and Biotechnology as part of the research project Sensitive Technologies and European Public Ethics (STEPE), funded by the Science in Society Programme of the EC’s Seventh Framework Programme for Research and Technological Development (FP7).

Social structure emerges via the interaction between local ecology and individual behaviour.

1. The formation of groups is a fundamental aspect of social organization, but there are still many questions regarding how social structure emerges from individuals making non-random associations. 2. Although food distribution and individual phenotypic traits are known to separately influence social organization, this is the first study, to our knowledge, experimentally linking them to demonstrate the importance of their interaction in the emergence of social structure. 3. Using an experimental design in which food distribution was either clumped or dispersed, in combination with individuals that varied in exploratory behaviour, our results show that social structure can be induced in the otherwise non-social European shore crab (Carcinus maenas). 4. Regardless of food distribution, individuals with relatively high exploratory behaviour played an important role in connecting otherwise poorly connected individuals. In comparison, low exploratory individuals aggregated into cohesive, stable subgroups (moving together even when not foraging), but only in tanks where resources were clumped. No such non-foraging subgroups formed in environments where food was evenly dispersed. 5. Body size did not accurately explain an individual's role within the network for either type of food distribution. 6. Because of their synchronized movements and potential to gain social information, groups of low exploratory crabs were more effective than singletons at finding food. 7. Because social structure affects selection, and social structure is shown to be sensitive to the interaction between ecological and behavioural differences among individuals, local selective pressures are likely to reflect this interaction.

Avaliação agronômica de híbridos interespecíficos entre capim-elefante e milheto

O objetivo deste trabalho foi avaliar o comportamento agronômico de híbridos entre capim-elefante (Pennisetum purpureum Schum.) e milheto (P. glaucum (E.) Leek), a fim de determinar seu potencial para o melhoramento da forragem e a seleção de híbridos para futuras avaliações. Foram utilizadas 12 cultivares de milheto e 11 clones de capim-elefante, cruzados em esquema de dialelo parcial. As 132 combinações híbridas, além de duas testemunhas, foram avaliadas em experimentos em blocos casualizados, com três repetições. Anotaram-se dados de produção de matéria seca, altura de plantas, porcentagem de matéria seca, relação entre folha e caule e de qualidade da forragem (porcentagem de proteína bruta, porcentagem de fibra em detergente neutro e ácido e digestibilidade in vitro da matéria orgânica). Foi verificada existência de variabilidade entre os híbridos interespecíficos de capim-elefante e milheto, na maioria das características. A superioridade de alguns híbridos, em relação às testemunhas, demonstra o potencial do cruzamento entre P. purpureum e P. glaucum para a obtenção de cultivares melhoradas. Considerando-se tanto características de produção como de qualidade da forragem, os melhores híbridos avaliados foram 108 (F91-2-5 x M-60), 53 (F93-4-2 x M-27), 35 (F94-28-3 x M-42), 36 (F94-28-3 x M-60) e 4 (F92-101-2 x M-35).

Renoncement aux soins: comment appréhender cette réalité en médecine de premier recours [Patients forgoing health care for economic reasons: how to identify this in a primary care setting?].

Although the performance of the Swiss health system is high, one out of ten patients in general practitioner's (GP) office declares having foregone care in the previous twelve months for economic reasons. Reasons for foregoing care are several and include a lack of knowledge of existing social aids in getting health insurance, unavailability of GPs and long waiting lists for various types of care. Although long term knowledge of patients or a psychosocial history of deprivation or poverty may help identify individuals at risk of foregoing care, many may remain undetected. We propose then a few instruments to help GPs to identify, in a simple and structured approach, patients at risk of forgoing care for economic reasons; these patients are frequently deprived and sometimes poor.

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

Medroxyprogesterone abrogates the inhibitory effects of estradiol on vascular smooth muscle cells by preventing estradiol metabolism.

Sequential conversion of estradiol (E) to 2/4-hydroxyestradiols and 2-/4-methoxyestradiols (MEs) by CYP450s and catechol-O-methyltransferase, respectively, contributes to the inhibitory effects of E on smooth muscle cells (SMCs) via estrogen receptor-independent mechanisms. Because medroxyprogesterone (MPA) is a substrate for CYP450s, we hypothesized that MPA may abrogate the inhibitory effects of E by competing for CYP450s and inhibiting the formation of 2/4-hydroxyestradiols and MEs. To test this hypothesis, we investigated the effects of E on SMC number, DNA and collagen synthesis, and migration in the presence and absence of MPA. The inhibitory effects of E on cell number, DNA synthesis, collagen synthesis, and SMC migration were significantly abrogated by MPA. For example, E (0.1micromol/L) reduced cell number to 51+/-3.6% of control, and this inhibitory effect was attenuated to 87.5+/-2.9% by MPA (10 nmol/L). Treatment with MPA alone did not alter any SMC parameters, and the abrogatory effects of MPA were not blocked by RU486 (progesterone-receptor antagonist), nor did treatment of SMCs with MPA influence the expression of estrogen receptor-alpha or estrogen receptor-beta. In SMCs and microsomal preparations, MPA inhibited the sequential conversion of E to 2-2/4-hydroxyestradiol and 2-ME. Moreover, as compared with microsomes treated with E alone, 2-ME formation was inhibited when SMCs were incubated with microsomal extracts incubated with E plus MPA. Our findings suggest that the inhibitory actions of MPA on the metabolism of E to 2/4-hydroxyestradiols and MEs may negate the cardiovascular protective actions of estradiol in postmenopausal women receiving estradiol therapy combined with administration of MPA.

Controle biológico de nematóides gastrintestinais de caprinos em clima semi-árido pelo fungo Monacrosporium thaumasium

O objetivo deste trabalho foi avaliar a viabilidade do fungo nematófago Monacrosporium thaumasium, no controle de larvas infectantes de nematóides gastrintestinais de caprinos em campo, no Semi-Árido cearense. Uma área de 20 ha, com pasto recém-formado, livre de vermes, foi dividida em quatro piquetes de 5 ha. Em cada piquete, foi formado um grupo constituído por nove caprinos, onde cada animal recebeu os seguintes tratamentos, durante os meses de abril a junho de 2002: grupo 1, 10 g de péletes por via oral, semanalmente; grupo 2, 10 g de péletes por via oral, quinzenalmente; grupo 3, 0,5 mL de moxidectin por 25 kg de peso vivo; grupo 4, controle, não tratado. Mensalmente, dois caprinos traçadores foram colocados junto ao rebanho por 30 dias, e após esse período, foram sacrificados e necropsiados. O grupo de animais que recebeu o tratamento com o fungo uma vez por semana apresentou redução no número de ovos por grama de fezes, menor carga parasitária e maior ganho de peso, em relação aos animais dos demais grupos. O fungo M. thaumasium é eficiente no controle de larvas infectantes nas pastagens e pode ser utilizado no controle e profilaxia de nematóides gastrintestinais de caprinos, no Semi-Árido cearense.

Processus de "deuil gelé" chez les femmes bosniaques, épouses de disparus

Les femmes concernées par cette recherche sont des femmes bosniaques, requérantes d'asile en Suisse, suivies au sein de l'association « Appartenances ». Elles ont quitté leur pays à la suite de la prise de la ville de Srebrenica, en juillet 1995. Lors de cet exode, elles ont été séparées de leurs maris, qui sont aujourd'hui encore portés disparus. Ces femmes partagent une expérience douloureuse qui transparaît derrière un certain nombre de symptômes physiques et psychiques. Nous avons été frappés par la répétition de pertes importantes, sans que les conditions permettant un travail de deuil soient réunies. Aucune signification ne peut être attribuée aux disparitions et aux décès, masqués par le silence politique et par l'impossibilité d'accomplir un rituel. Le deuil peut ainsi se compliquer jusqu'à devenir un deuil impossible, dont le prototype pourrait être le « deuil gelé » lors d'une disparition. D'autre part, le stress et l'attaque de l'identité occasionnés par les traumatismes et l'exil ont coupé ces femmes de leurs ressources personnelles et culturelles. La perte d'une image entière de soi est prolongée par le statut précaire de requérant d'asile et par la perte des espoirs mis dans le pays d'accueil. Devant la complexité de cette problématique, nous nous sommes demandés sur quel aspect axer la prise en charge thérapeutique. Nous avons décidé de travailler sur le vécu et les deuils actuels de ces patientes (stress post-traumatique et statut précaire en Suisse). Le concept-clé qui a étayé cette recherche s'inspire de Pollock (7): « le processus de deuil devient très significatif, dans le sens qu 'il est apparemment une des formes les plus universelles de l'adaptation et de la croissance à travers la structuration, disponible pour l'homme. » Dès lors, nous avons fait l'hypothèse que si le deuil est une forme universelle d'adaptation, l'élaboration d'un travail de deuil ou d'un processus d'adaptation quel qu'il soit, pourra servir d'apprentissage pour l'élaboration d'autres deuils. Concrètement, en travaillant sur le rétablissement de leur identité, les femmes pourront retrouver un accès à leurs ressources personnelles et culturelles, tandis que travailler sur les espoirs et déceptions face au statut en Suisse permettra de développer des moyens permettant plus de contrôle sur l'environnement. Leur autonomie rétablie, elles pourront consacrer leurs énergies à attribuer une signification à leur vécu et faire face aux autres deuils paralysant leur guérison. Nous avons assisté aux entretiens thérapeutiques, en récoltant des témoignages sur la base d'un canevas d'entretien semi-structuré, puis nous avons transposé les éléments sur une grille d'analyse regroupant les informations en items. L'analyse de ces entretiens nous a permis de préciser notre hypothèse et de développer des pistes de réflexion pour l'accompagnement thérapeutique de personnes vivant une disparition. A l'issue de ce travail, nous pouvons tirer des parallèles entre les processus d'élaboration des divers deuils. Les femmes sont entrées peu à peu dans le souvenir de la personne aimée et non plus dans le souvenir des événements traumatiques qui ont marqué sa disparition. S'appuyant alors sur la « mémoire sereine » de Kristeva (1) une recherche de signification a pu être entreprise, rejoignant ce que Métraux et Fleuiy (43) définissent comme la santé : « ... se voir créateur du sens qu'on veut donner à sa propre existence, à ses actes et à ses projets. »

No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels.

Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.