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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.
Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition
Body fat measurement by bioelectrical impedance and air displacement plethysmography: a cross-validation study to design bioelectrical impedance equations in Mexican adults
<p>Abstract</p> <p>Background</p> <p>The study of body composition in specific populations by techniques such as bio-impedance analysis (BIA) requires validation based on standard reference methods. The aim of this study was to develop and cross-validate a predictive equation for bioelectrical impedance using air displacement plethysmography (ADP) as standard method to measure body composition in Mexican adult men and women.</p> <p>Methods</p> <p>This study included 155 male and female subjects from northern Mexico, 20–50 years of age, from low, middle, and upper income levels. Body composition was measured by ADP. Body weight (BW, kg) and height (Ht, cm) were obtained by standard anthropometric techniques. Resistance, R (ohms) and reactance, Xc (ohms) were also measured. A random-split method was used to obtain two samples: one was used to derive the equation by the "all possible regressions" procedure and was cross-validated in the other sample to test predicted versus measured values of fat-free mass (FFM).</p> <p>Results and Discussion</p> <p>The final model was: FFM (kg) = 0.7374 * (Ht<sup>2 </sup>/R) + 0.1763 * (BW) - 0.1773 * (Age) + 0.1198 * (Xc) - 2.4658. R<sup>2 </sup>was 0.97; the square root of the mean square error (SRMSE) was 1.99 kg, and the pure error (PE) was 2.96. There was no difference between FFM predicted by the new equation (48.57 ± 10.9 kg) and that measured by ADP (48.43 ± 11.3 kg). The new equation did not differ from the line of identity, had a high R<sup>2 </sup>and a low SRMSE, and showed no significant bias (0.87 ± 2.84 kg).</p> <p>Conclusion</p> <p>The new bioelectrical impedance equation based on the two-compartment model (2C) was accurate, precise, and free of bias. This equation can be used to assess body composition and nutritional status in populations similar in anthropometric and physical characteristics to this sample.</p
Effects of early feeding on growth velocity and overweight/obesity in a cohort of HIV unexposed South African infants and children
BACKGROUND: South Africa has the highest prevalence of overweight/obesity in Sub-Saharan Africa. Assessing the
effect of modifiable factors such as early infant feeding on growth velocity and overweight/obesity is therefore important.
This paper aimed to assess the effect of infant feeding in the transitional period (12 weeks) on 12–24 week growth
velocity amongst HIV unexposed children using WHO growth velocity standards and on the age and sex adjusted body
mass index (BMI) Z-score distribution at 2 years.
METHODS: Data were from 3 sites in South Africa participating in the PROMISE-EBF trial. We calculated growth velocity
Z-scores using the WHO growth standards and assessed feeding practices using 24-hour and 7-day recall data. We used
quantile regression to study the associations between 12 week infant feeding and 12–24 week weight velocity (WVZ) with
BMI-for-age Z-score at 2 years. We included the internal sample quantiles (70th and 90th centiles) that approximated the
reference cut-offs of +2 (corresponding to overweight) and +3 (corresponding to obesity) of the 2 year BMI-for-age Z-scores.
RESULTS: At the 2-year visit, 641 children were analysed (median age 22 months, IQR: 17–26 months). Thirty
percent were overweight while 8.7% were obese. Children not breastfed at 12 weeks had higher 12–24 week mean WVZ
and were more overweight and obese at 2 years. In the quantile regression, children not breastfed at 12 weeks had a 0.37
(95% CI 0.07, 0.66) increment in BMI-for-age Z-score at the 50th sample quantile compared to breast-fed children. This difference
in BMI-for-age Z-score increased to 0.46 (95% CI 0.18, 0.74) at the 70th quantile and 0.68 (95% CI 0.41, 0.94) at the 90th
quantile . The 12–24 week WVZ had a uniform independent
effect across the same quantiles.
CONCLUSIONS: This study demonstrates that the first 6 months of life is a critical period in the development of childhood
overweight and obesity. Interventions targeted at modifiable factors such as early infant feeding practices may reduce the
risks of rapid weight gain and subsequent childhood overweight/obesity.Scopu
DNA methylation and gene expression of HIF3A: cross-tissue validation and associations with BMI and insulin resistance
Weber and church governance: religious practice and economic activity
The debate about the relationship between religion and economic activity in the wake of Weber has been cast largely in terms of belief and values. This article suggests an alternative focus on practice. It argues that taken for granted practices of church governance formed to-hand resources for the organization of economic activity. The argument is developed through an examination of the historical development of church governance practices in the Presbyterian Church of Scotland, with particular emphasis on the way in which theological belief gave rise to practices of accountability and record keeping. In turn such practices contributed to a ‘culture of organization’ which had implications for economic activity. A focus on governance practices can help to illuminate enduring patterns of difference in the organization of economic activity
Religious Tastes and Styles as Markers of Class Belonging: A Bourdieuian Perspective on Pentecostalism in South America
Studies on the relationship between social class and religion tend to highlight the demographic dimension of class, but neglect its symbolic dimension. By addressing the symbolic dimensions through a Bourdieuian approach, this article contends that religious tastes and styles can be employed as class markers within the sphere of religion. A case study on Argentinean Pentecostalism and in-depth analysis of a lower and middle class church illustrate how symbolic class differences are cultivated in the form of distinctive religious styles. While the lower class church displays a style marked by emotional expressiveness and the search for life improvement through spiritual practices, the middle class church performs a sober and calm style of Pentecostalism. The study highlights the role of styles in the reproduction of class boundaries, while shedding a critical light on the importance of tastes
Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity
Decline in age at menarche among Spanish women born from 1925 to 1962
<p>Abstract</p> <p>Background</p> <p>While the timing of reproductive events varies across populations, a downward trend in age at menarche has nevertheless been reported in most of the developed world over the past century. Given the impact of change in age at menarche on health conditions, this study sought to examine secular trends in age at menarche among women living in Navarre (Northern Spain) who participated in a population-based breast cancer screening programme.</p> <p>Methods</p> <p>The study was based on 110545 women born from 1925 to 1962. Trends were tested using a linear regression model, in which year of birth was entered continuously as the predictor and age at menarche (years) as the response variable, using size of town and region of birth as covariates.</p> <p>Results</p> <p>Among women born in Navarre between 1925 and 1962, age at menarche declined steadily from an average of 13.72 years in the 1925-1929 birth-cohorts to 12.83 years in the 1958-1962 birth-cohorts. Controlling for size of town or city of birth, age at menarche declined by an average of 0.132 years every 5 years over the period 1925-1962. This decline was greater in women born in rural versus urban settings. Trends were also different among regions of birth.</p> <p>Conclusion</p> <p>We report a population-based study showing a downward trend in age of onset of menarche among Spanish women born in the period 1925-1962, something that is more pronounced among women born in rural settings and varies geographically.</p
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