Genome-wide linkage scan reveals multiple susceptibility loci influencing lipid and lipoprotein levels in the Québec Family Study

A genome-wide linkage study was performed to identify chromosomal regions harboring genes influencing lipid and lipoprotein levels. Linkage analyses were conducted for four quantitative lipoprotein/lipid traits, i.e., total cholesterol, triglyceride, HDL-cholesterol (HDL-C), and LDL-C concentrations, in 930 subjects enrolled in the Québec Family Study. A maximum of 534 pairs of siblings from 292 nuclear families were available. Linkage was tested using both allele-sharing and variance-component linkage methods. The strongest evidence of linkage was found on chromosome 12q14.1 at marker D12S334 for HDL-C, with a logarithm of the odds (LOD) score of 4.06. Chromosomal regions harboring quantitative trait loci (QTLs) for LDL-C included 1q43 (LOD = 2.50), 11q23.2 (LOD = 3.22), 15q26.1 (LOD = 3.11), and 19q13.32 (LOD = 3.59). In the case of triglycerides, three markers located on 2p14, 11p13, and 11q24.1 provided suggestive evidence of linkage (LOD > 1.75). Tests for total cholesterol levels yielded significant evidence of linkage at 15q26.1 and 18q22.3 with the allele-sharing linkage method, but the results were nonsignificant with the variance-component method. In conclusion, this genome scan provides evidence for several QTLs influencing lipid and lipoprotein levels. Promising candidate genes were located in the vicinity of the genomic regions showing evidence of linkage

Probabilistic analysis of the upwind scheme for transport

We provide a probabilistic analysis of the upwind scheme for multi-dimensional transport equations. We associate a Markov chain with the numerical scheme and then obtain a backward representation formula of Kolmogorov type for the numerical solution. We then understand that the error induced by the scheme is governed by the fluctuations of the Markov chain around the characteristics of the flow. We show, in various situations, that the fluctuations are of diffusive type. As a by-product, we prove that the scheme is of order 1/2 for an initial datum in BV and of order 1/2-a, for all a>0, for a Lipschitz continuous initial datum. Our analysis provides a new interpretation of the numerical diffusion phenomenon

Familial resemblance in eating behaviors in men and women from the Quebec Family Study

Objective: It is commonly recognized that genetic, environmental, behavioral, and social factors are involved in the development of obesity. The family environment may play a key role in shaping children's eating behaviors. The purpose of this study was to estimate the degree of familial resemblance in eating behavioral traits (cognitive dietary restraint, disinhibition, and susceptibility to hunger). Research Methods and Procedures: Eating behavioral traits were assessed with the Three-Factor Eating Questionnaire in 282 men and 402 women (202 families) from the Quebec Family Study. Familial resemblance for each trait (adjusted for age, sex, and BMI) was investigated using a familial correlation model. Results: The pattern of familial correlation showed significant spouse correlation for the three eating behavior phenotypes, as well as significant parent-offspring and sibling correlations for disinhibition and susceptibility to hunger. According to the most parsimonious model, generalized heritability estimates (including genetic and shared familial environmental effects) reached 6%, 18%, and 28% for cognitive dietary restraint, disinhibition, and susceptibility to hunger, respectively. Discussion: These results suggest that there is a significant familial component to eating behavioral traits but that the additive genetic component appears to be small, with generalized heritability estimates ranging from 6% to 28%. Thus, non-familial environmental factors and gene-gene and gene-environmental interactions seem to be the major determinants of the eating/behavioral traits

Drugs Associated with More Suicidal Ideations Are also Associated with More Suicide Attempts

In randomized controlled trials (RCTs), some drugs, including CB1 antagonists for obesity treatment, have been shown to cause increased suicidal ideation. A key question is whether drugs that increase or are associated with increased suicidal ideations are also associated with suicidal behavior, or whether drug-induced suicidal ideations are unlinked epiphenomena that do not presage the more troubling and potentially irrevocable outcome of suicidal behavior. This is difficult to determine in RCTs because of the rarity of suicidal attempts and completions.To determine whether drugs associated with more suicidal ideations are also associated with more suicide attempts in large spontaneous adverse event (AE) report databases.Generalized linear models with negative binomial distribution were fitted to Food and Drug Administration (FDA) Adverse Event (AE) Reporting System (AERS) data from 2004 to 2008. A total of 1,404,470 AEs from 832 drugs were analyzed as a function of reports of suicidal ideations; other non-suicidal adverse reactions; drug class; proportion of reports from males; and average age of subject for which AE was filed. Drug was treated as the unit of analysis, thus the statistical models effectively had 832 observations.Reported suicide attempts and completed suicides per drug.832 drugs, ranging from abacavir to zopiclone, were evaluated. The 832 drugs, as primary suspect drugs in a given adverse event, accounted for over 99.9% of recorded AERS. Suicidal ideations had a significant positive association with suicide attempts (p<.0001) and had an approximately 131-fold stronger magnitude of association than non-suicidal AERs, after adjusting for drug class, gender, and age.In AE reports, drugs that are associated with increased suicidal ideations are also associated with increased suicidal attempts or completions. This association suggests that drug-induced suicidal ideations observed in RCTs plausibly represent harbingers that presage the more serious suicide attempts and completions and should be a cause for concern

Dual-Energy X-Ray Absorptiometry for Quantification of Visceral Fat

Obesity is the major risk factor for metabolic syndrome and through it diabetes as well as cardiovascular disease. Visceral fat (VF) rather than subcutaneous fat (SF) is the major predictor of adverse events. Currently, the reference standard for measuring VF is abdominal X-ray computed tomography (CT) or magnetic resonance imaging (MRI), requiring highly used clinical equipment. Dual-energy X-ray absorptiometry (DXA) can accurately measure body composition with high-precision, low X-ray exposure, and short-scanning time. The purpose of this study was to validate a new fully automated method whereby abdominal VF can be measured by DXA. Furthermore, we explored the association between DXA-derived abdominal VF and several other indices for obesity: BMI, waist circumference, waist-to-hip ratio, and DXA-derived total abdominal fat (AF), and SF. We studied 124 adult men and women, aged 18–90 years, representing a wide range of BMI values (18.5–40 kg/m2) measured with both DXA and CT in a fasting state within a one hour interval. The coefficient of determination (r2) for regression of CT on DXA values was 0.959 for females, 0.949 for males, and 0.957 combined. The 95% confidence interval for r was 0.968 to 0.985 for the combined data. The 95% confidence interval for the mean of the differences between CT and DXA VF volume was −96.0 to −16.3 cm3. Bland–Altman bias was +67 cm3 for females and +43 cm3 for males. The 95% limits of agreement were −339 to +472 cm3 for females and −379 to +465 cm3 for males. Combined, the bias was +56 cm3 with 95% limits of agreement of −355 to +468 cm3. The correlations between DXA-derived VF and BMI, waist circumference, waist-to-hip ratio, and DXA-derived AF and SF ranged from poor to modest. We conclude that DXA can measure abdominal VF precisely in both men and women. This simple noninvasive method with virtually no radiation can therefore be used to measure VF in individual patients and help define diabetes and cardiovascular risk

Impact of a non-restrictive satiating diet on anthropometrics, satiety responsiveness and eating behaviour traits in obese men displaying a high or a low satiety phenotype

The aim of this study was to evaluate the impact of a non-restrictive satiating diet in men displaying various degrees of satiety efficiency. In all, sixty-nine obese men aged 41·5 (sd 5·7) years were randomly assigned to a control (10–15, 55–60 and 30 % energy as protein, carbohydrate and lipid, respectively; n 34) or satiating (20–25, 45–50 and 30–35 % energy as protein, carbohydrate and lipid, respectively; n 35) diet for 16 weeks, and were classified as having a low (LSP) or high (HSP) satiety phenotype. Both diets were consumed ad libitum. Changes in body weight, BMI, percent fat mass, waist circumference, satiety responsiveness and eating behaviour traits were assessed following the intervention. Dropout rates were higher in the control diet (44·1 %) compared with the satiating diet (8·6 %). Decreases in body weight, BMI and waist circumference were significant in both groups, yet HSP individuals lost more body weight than LSP individuals (P=0·048). Decreases in % fat mass were greater in the satiating diet (LSP: −2·1 (sd 2·1) %; P<0·01 and HSP: −3·0 (sd 2·5) %; P<0·001) compared with the control diet (LSP: −1·1 (sd 2·5) % and HSP: −1·3 (sd 2·6) %) (P=0·034). Satiety responsiveness was markedly improved in the satiating diet, whereas no significant changes were observed in the control group. Changes in dietary restraint (+3·3 (sd 2·9) to +7·2 (sd 5·5)), flexible control (+0·9 (sd 1·4) to +2·3 (sd 2·7)), rigid control (+2·2 (sd 1·5) to +2·5 (sd 2·8)), disinhibition (−2·8 (sd 3·7) to −3·2 (sd 2·6)) and susceptibility to hunger (−2·7 (sd 4·1) to −4·6 (sd 3·9)) were similar between the diets. Compared with the control diet, the satiating diet favoured adherence, decreased % fat mass and improved satiety responsiveness in both HSP and LSP individuals

Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation (PERSPECTIVE I&I).

Early detection of breast cancer through screening reduces breast cancer mortality. The benefits of screening must also be considered within the context of potential harms (e.g., false positives, overdiagnosis). Furthermore, while breast cancer risk is highly variable within the population, most screening programs use age to determine eligibility. A risk-based approach is expected to improve the benefit-harm ratio of breast cancer screening programs. The PERSPECTIVE I&I (Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation) project seeks to improve personalized risk assessment to allow for a cost-effective, population-based approach to risk-based screening and determine best practices for implementation in Canada. This commentary describes the four inter-related activities that comprise the PERSPECTIVE I&I project. 1: Identification and validation of novel moderate to high-risk susceptibility genes. 2: Improvement, validation, and adaptation of a risk prediction web-tool for the Canadian context. 3: Development and piloting of a socio-ethical framework to support implementation of risk-based breast cancer screening. 4: Economic analysis to optimize the implementation of risk-based screening. Risk-based screening and prevention is expected to benefit all women, empowering them to work with their healthcare provider to make informed decisions about screening and prevention