Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.

BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction)  = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio  = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio  = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Indice d'aptitude général pour le WISC-IV: Normes francophones

La quatrième version de l'échelle d'intelligence de Wechsler pour enfants (WISC-IV) permet le calcul du QI Total et de quatre indices factoriels : compréhension verbale, raisonnement perceptif, vitesse de traitement et mémoire de travail. En 1998, Prifitera et al, ont préconisé le calcul de l'indice d'aptitude général (IAG) comme alternative au quotient intellectuel total (QIT), et cela à partir des scores de compréhension verbale et de raisonnement perceptif. La première étude présentée dans cet article a pour objectif d'établir les normes francophones pour le score IAG du WISC-IV, en utilisant une procédure d'approximation statistique. La deuxième étude vise à examiner la validité de ces normes, en les confrontant à des données recueillies sur un échantillon de 60 enfants. La corrélation entre QIT et IAG est de 0,91 et la différence relative moyenne de 0,18 point. Ces normes permettent d'utiliser le score IAG comme alternative au QIT dans certaines situations diagnostiques.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

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.

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

西學凡Xi xue fan.Sur les sciences européennes.

Cat. imp., liv. 125, f. 31.Par le P. Aleni (1582-1649). Préfaces de Yang Ting jun (1623), de He Yi yuan (1626). Postface de Xiong Shi qi. Gravé par la mission du Fu jian, à la salle Qin yi, sans date.

御選古文淵鑑Yu xuan gu wen yuan jian.Recueil de textes anciens préparé par ordre impérial.

Contient : période antérieure aux Qin, livres 1 à 8 ; dynastie des Qin, livre 9 ; dynastie des Han, livres 10 à 20 ; période des Trois Royaumes, livres 21 et 22 ; dynastie des Jin, livres 23 et 24 ; dynastie des Song, livre 25 ; dynasties des Qi, Liang, Chen, livre 26 ; dynastie des Wei septentrionaux, livre 27 ; dynasties des Qi septentrionaux, Zhou septentrionaux, Sui, livre 28 ; dynastie des Tang, livres 29 à 40 ; période des Cinq Dynasties, livre 41 ; dynastie des Song, livres 42 à 64

Chinois 1016

Contient : IDa xi xi tai li xian sheng xing ji ; II思及先生行蹟Si ji xian sheng xing ji ; III思及艾先生語錄Si ji ai xian sheng yu lu ; IV V楊淇園先生事蹟Yang qi yuan xian sheng shi ji.Vie de Yang Qi yuan ; VI-VIII張彌格爾遺蹟Zhang mi ke er yi ji ; IX悌尼削世紀Di ni xiao shi ji.Vie de Denis

張議Zhang zhi.Vie de Zhang Zhi, chrétien.

Ce personnage naquit vers 1605. Ouvrage de Xiong Shi qi (XVIIe ou XVIIIe siècle).

熙朝崇正集Xi chao chong zheng ji.Monuments de la religion chrétienne.

Stèle de Xi an fu, croix de Wen ling, décrets et rapports : mémoires de Xu Guang qi, Zhang Geng, etc., publiés par l'église du Fu jian (1638) à Quan zhou.2 livres.

Français 821

Contient : 1° Roman d'Hercule ; 2° « Ici commence de ciaus d'Athenes et de ciaus de l'isle de Crete... », extrait de l' « Histoire ancienne depuis la création », relatif à Hercule et aux Amazones ; 3° « Liber Catonis », traduit par « MACE de Troie » ; 4° « Optimum documentum de regimine familie », lettre (supposée) de saint BERNARD à Raymond de Château d'Amboise ; 5° « La Complainte de la tribulation del mirable phylosophe qi fu appelez BOECES, et de la Consolation de la phylosophye », traduction anonyme, avec prologue et conclusion ; 6° « La Ystoire dou Nostre Seignor Jhesu Crist, et coment il soufri passion et torment et mort pour sauvement de la humaine generation » ; 7° Enseignements à Alexandre, en prose, suivis des Dits des Sages ; 8° « De dous Roiaumes dou monde et des aages dou siecle et des rois qi regnerent ça en arieres... », abrégé d'histoire universelle ; 9° Roman de la Guerre de Troie, par BENEOIT DE SAINTE MORE » ; 10° Extrait de l' « Histoire ancienne depuis la création », contenant les origines romaines, depuis Enée jusqu'à la mort de Romulus ; 11° Roman de Landomata, fils d'Hector, en prose ; 12° Histoire du roi Alexandre (d'après le Pseudo-Callisthène)

新刊繡像清風閘全傳Xin kan xiu xiang qing feng zha quan zhuan.Nouvelle histoire illustrée de l'écluse de Qing feng.

Préface par Mei qi zhu ren (1819). Portraits des personnages, époque de Ren zong des Song. Édition du pavillon Hua xian (1821).4 livres (32 hui).

新鐫繡像西廂琵琶合刻Xin juan xiu xiang xi xiang pi pa he ke.Histoire du pavillon occidental et Histoire du luth, nouvelle édition collective illustrée.

Contient : I園林午夢Yuan lin wu meng.Songe de midi dans le bosquet ; II圍棋馬局Wei qi ma ju.L'échiquier ; III西廂摘句骰譜Xi xiang zhe ju tou pu.Tableaux explicatifs des parties de dés du Xi xiang ji ; IV錢塘夢Qian tang meng.Songe de Qian tang ; V會眞記Hui zhen ji.Histoire du portrait ; VI李卓吾先生（alias 卓老）批㸃西廂記眞本Li zhuo wu xian sheng (alias tcho lao) pi dian xi xiang ji zhen ben.Le Xi xiang ji (Histoire du pavillon occidental), ponctué par Li Zhuo wu ; VII新校琵琶記始末Xin jiao pi pa ji shi mo.Le Pi pa ji (Histoire du luth), édition revue

砥石齋二種曲Zhi shi zhai er zhong qu.Deux pièces du pavillon Zhi shi.

Contient : I詩扇記傳奇Shi shan ji chuan qi.Histoire d'un éventail avec une ode ; II夢裏緣傳奇Meng li yuan chuan qi.La fortune en songe ; III砥石齋韻品雜齣Zhi shi zhai yun pin za chu.Scènes diverses avec poésies du pavillon Zhi shi ; IV賞心幽品四種Shang xin you pin si zhong.Quatre scènes pour réjouir le fond du cœur ; V破牢愁Po lao chou .Le chagrin de l'appui brisé ; VI砥石齋散 (sic) 曲Zhi shi zhai san qu.Scènes diverses du pavillon Zhi shi