Comparison of year-of-exam- and age-matched estimates of heritability in the Framingham Heart Study data

Several different approaches can be used to examine generational and temporal trends in family studies. The measurement of offspring and parents can be made over a short period of time with parents and offspring having quite different ages, or measurements can be made at the same ages but with decades between parent and offspring measures. A third approach, used in the Framingham Heart Study, has repeated examinations across a broad range of age and time, and provides a unique opportunity to compare these approaches. Parents and offspring were matched both on (year of exam) and on age. Heritability estimates for systolic blood pressure, body mass index, height, weight, cholesterol, and glucose were obtained by regressing offspring on midparent values with and without adjustment for age. Higher estimates of heritability were obtained for age-matched than for year-of-exam-matched data for all traits considered. For most traits, estimates of the heritability of the change over time (slope) of the trait were near zero. These results suggest that the optimal design to identify genetic effects in traits with large age-related effects may be to measure parents and offspring at similar ages and not to rely on age-adjustment or longitudinal measures to account for these temporal effects

Parental socioeconomic position and development of overweight in adolescence: longitudinal study of Danish adolescents

<p>Abstract</p> <p>Background</p> <p>An inverse social gradient in overweight among adolescents has been shown in developed countries, but few studies have examined whether weight gain and the development of overweight differs among adolescents from different socioeconomic groups in a longitudinal study. The objective was to identify the possible association between parental socioeconomic position, weight change and the risk of developing overweight among adolescents between the ages 15 to 21.</p> <p>Methods</p> <p>Prospective cohort study conducted in Denmark with baseline examination in 1996 and follow-up questionnaire in 2003 with a mean follow-up time of 6.4 years. A sample of 1,656 adolescents participated in both baseline (mean age 14.8) and follow-up (mean age 21.3). Of these, 1,402 had a body mass index (BMI = weight/height²kg/m²) corresponding to a value below 25 at baseline when adjusted for age and gender according to guidelines from International Obesity Taskforce, and were at risk of developing overweight during the study period. The exposure was parental occupational status. The main outcome measures were change in BMI and development of overweight (from BMI < 25 to BMI > = 25).</p> <p>Results</p> <p>Average BMI increased from 21.3 to 22.7 for girls and from 20.6 to 23.6 in boys during follow-up. An inverse social gradient in overweight was seen for girls at baseline and follow-up and for boys at follow-up. In the full population there was a tendency to an inverse social gradient in the overall increase in BMI for girls, but not for boys. A total of 13.4% developed overweight during the follow-up period. Girls of lower parental socioeconomic position had a higher risk of developing overweight (OR's between 4.72; CI 1.31 to 17.04 and 2.03; CI 1.10-3.74) when compared to girls of high parental socioeconomic position. A tendency for an inverse social gradient in the development of overweight for boys was seen, but it did not meet the significance criteria</p> <p>Conclusions</p> <p>The levels of overweight and obesity among adolescents are high and continue to rise. Results from this study suggest that the inverse social gradient in overweight becomes steeper for girls and emerges for boys in late adolescence (age span 15 to 21 years). Late adolescence seems to be an important window of opportunity in reducing the social inequality in overweight among Danish adolescents.</p

Multi-Tissue Epigenetic analysis Identifies Distinct associations Underlying insulin Resistance and alzheimer\u27s Disease at Cpt1A Locus

BACKGROUND: Insulin resistance (IR) is a major risk factor for Alzheimer\u27s disease (AD) dementia. The mechanisms by which IR predisposes to AD are not well-understood. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus improving our understanding of the biological and regulatory mechanisms linking IR and AD. METHODS: We conducted an epigenome-wide association study of IR, quantified using the homeostatic model assessment of IR (HOMA-IR) and adjusted for body mass index, in 3,167 participants from the Framingham Heart Study (FHS) without type 2 diabetes at the time of blood draw used for methylation measurement. We identified DNA methylation markers associated with IR at the genome-wide level accounting for multiple testing (P \u3c 1.1 × 10 RESULTS: We confirmed the strong association of blood DNA methylation with IR at three loci (cg17901584-DHCR24, cg17058475-CPT1A, cg00574958-CPT1A, and cg06500161-ABCG1). In FHS, higher levels of blood DNA methylation at cg00574958 and cg17058475 were both associated with lower IR (P = 2.4 × 10 CONCLUSIONS: Our results suggest potentially distinct epigenetic regulatory mechanisms between peripheral blood and dorsolateral prefrontal cortex tissues underlying IR and AD at CPT1A locus

Common TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis

<p>Abstract</p> <p>Background</p> <p>Several studies have investigated single nucleotide polymorphisms (SNPs) in candidate genes associated with sepsis and septic shock with conflicting results. Only few studies have combined the analysis of multiple SNPs in the same population.</p> <p>Methods</p> <p>Clinical data and DNA from consecutive adult patients with culture proven Gram negative bacteremia admitted to a Danish hospital between 2000 and 2002. Analysis for commonly described SNPs of tumor necrosis-α, (TNF-α), interleukin-1β (IL-1β), plasminogen activator-1 (PAI-1), urokinase plasminogen activator (uPA), CD14 and toll-like receptor 4 (TLR4) was done.</p> <p>Results</p> <p>Of 319 adults, 74% had sepsis, 19% had severe sepsis and 7% were in septic shock. No correlation between severity or outcome of sepsis was observed for the analyzed SNPs of TNF-α, IL-1β, PAI-1, uPA, CD14 or TLR-4. In multivariate Cox proportional hazard regression analysis, increasing age, polymicrobial infection and haemoglobin levels were associated with in-hospital mortality.</p> <p>Conclusion</p> <p>We did not find any association between TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms and outcome of Gram negative sepsis. Other host factors appear to be more important than the genotypes studied here in determining the severity and outcome of Gram negative sepsis.</p

Listening to patients: using verbal data in the validation of the Aberdeen Measures of Impairment, Activity Limitation and Participation Restriction (Ab-IAP)

Peer reviewedPublisher PD

Paracrine effects of TLR4-polarised mesenchymal stromal cells are mediated by extracellular vesicles

Mesenchymal stromal cells (MSCs) are adult stem cells able to give rise to bone, cartilage and fat cells. In addition, they possess immunomodulatory and immunosuppressive properties that are mainly mediated through secretion of extracellular vesicles (EVs). In a previous issue of Journal of Translational Medicine, Ti and colleagues demonstrated that preconditioning of MSCs with bacterial lipopolysaccharides results in secretion of EVs that can polarise mac‑ rophages towards anti-inflammatory M2 phenotype. Moreover, the authors suggest that EVs of lipopolysaccharide (LPS)-treated MSCs are superior to EVs of untreated MSCs concerning their ability to support wound healing. Our commentary critically discusses parallel efforts of other laboratories to generate conditioned media from stem cells for therapeutic applications, and highlights impact and significance of the study of Ti et al. Finally, we summarise its limitations and spotlight areas that need to be addressed to better define the underlying molecular mechanisms

Education Modifies Genetic and Environmental Influences on BMI

Obesity is more common among the less educated, suggesting education-related environmental triggers. Such triggers may act differently dependent on genetic and environmental predisposition to obesity. In a Danish Twin Registry survey, 21,522 twins of same-sex pairs provided zygosity, height, weight, and education data. Body mass index (BMI = kg weight/ m height2) was used to measure degree of obesity. We used quantitative genetic modeling to examine how genetic and shared and nonshared environmental variance in BMI differed by level of education and to estimate how genetic and shared and nonshared environmental correlations between education and BMI differed by level of education, analyzing women and men separately. Correlations between education and BMI were −.13 in women, −.15 in men. High BMI's were less frequent among well-educated participants, generating less variance. In women, this was due to restriction of all forms of variance, overall by a factor of about 2. In men, genetic variance did not vary with education, but results for shared and nonshared environmental variance were similar to those for women. The contributions of the shared environment to the correlations between education and BMI were substantial among the well-educated, suggesting importance of familial environmental influences common to high education and lower BMI. Family influence was particularly important in linking high education and lower levels of obesity