Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: The Diabetes Prevention Program

Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04–1×10⁻¹⁷). Except for total HDL particles (r = −0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial |r| = 0.07–0.17, P = 5×10⁻⁵–1×10⁻¹⁹). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10⁻⁵, P _interaction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = −0.03, SEE±0.22 mg/dl/allele, P = 0.90; P _interaction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, P _interaction = 0.01) but not in the placebo (β = −0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; P _interaction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.     

Women's status and infant mortality in rural Colombia

This paper investigates the effects of maternal demographic characteristics and social and economic statuses on infant mortality in rural Colombia. Demographic characteristics include the age of the mother, parity and length of preceding interbirth interval, and sex of infant. Measures of women's status at the time of birth include education, wage labor and occupation, economic stratum, place of residence, and whether the mother is living with a husband. The life history data for the study (involving 4,928 births) were collected in 1986 from a representative sample of two cohorts of women resident in rural central Colombia. Overall differentials in infant mortality by measures of women's status are small and are in good part associated with the differing reproductive behaviors of the women and variations in breastfeeding practices. The sharp declines in infant mortality recorded in rural Colombia in recent years appear less related to improved status of women than to reductions in fertility that enhance infant survivorship and to public health interventions shared by all segments of the population.     

Cytologic features of subependymal giant cell astrocytom: a review of 7 cases

OBJECTIVE: To describe the cytologic features of subependymal giant cell astrocytoma (SEGA) on smears and analyze cytomorphologic parameters that may help in reaching the diagnosis of SEGA. STUDY DESIGN: Cytologic smears of 7 cases of SEGA were reviewed and graded semi-quantitatively for 11 cytologic features: clustering, cytoplasmic fibrillary processes (fibrillarity), cellularity, small prominent nudcleoli, binucleation or multinucleation, "strap cells", spindle-shaped cells, mitoses, intranuclear inclusions, nuclear atypia and perivascular palisading/pseudorosettes. Corresponding histologic sections were also reviewed. RESULTS: The study included 5 male and 2 female patients with an average age of 8.3 years (range, 3-16) at surgery. Cytologic examination revealed loosely cohesive clusters of large cells possessing round to oval nuclei with no or minimal atypia; fine, evenly distributed chromatin; and abundant eosinophilic cytoplasm enmeshed in abundant thin, hairlike processes. Predominant features included hypercellularity, cell clustering, and fibrillarity. Binucleation or multinucleation; small, prominent nucleoli; and strap cells were often seen. Although common in histologic sections, perivascular palisading/pseudorosettes and spindled astrocytic cells were rarely noted on smears. CONCLUSION: The cytologic features of SEGA are highly characteristic and thus are of great use in supporting a diagnosis of SEGA and in excluding mimics, primarily gemistocytic astrocytoma and ependymoma.     

Integrating multiple data sources for assessing blue whale abundance and distribution in Chilean Northern Patagonia

Aim

Species distribution models are useful tools for depicting important habitat, assessing abundance and orienting conservation efforts. For small populations in poorly studied ecosystems, available data are often scarce and patchy. To overcome this limitation, we aim to evaluate the use of different data types within a hierarchical Bayesian framework with the goal of modelling the abundance and distribution of a small and highly migratory population of blue whale (BW, Balaenoptera musculus) summering in Chilean Northern Patagonian (CNP).

Location

CNP, Eastern South Pacific (ESP).

Methods

We constructed a Bayesian hierarchical species distribution Model (HSDM), combining a binomial N‐mixture model used to model BW groups counts in line‐transect data (2009, 2012 and 2014) with a logistic regression for modelling presence‐availability data (2009–2016), allowing both models to share covariate parameters for borrowing strength in estimations.

Results

Distance to areas of high chlorophyll‐a concentration during spring before summering season (AHCC‐s) was the most important and consistent explanatory variable for assessing BW abundance and distribution in CNP. Incorporating accessorial presence‐only data reduced uncertainty in parameters estimation when comparing with a model using only line‐transect data, although other covariates of secondary importance failed to be retained in this model.

Main conclusions

Our results remark the capability of HSDM for integrating different data types providing a potential powerful tool when data are limited and heterogeneous. Results indicate that AHCC‐s, and possibly thermal fronts, could modulate BW abundance and distribution patterns in CNP. Preliminary model‐based delimitations of possible priority conservation areas for BW in CNP overlap with highly used vessel navigation routes and areas destined to aquaculture.

     

Metabolite profiles and the risk of developing diabetes

Emerging technologies allow the high-throughput profiling of metabolic status from a blood specimen (metabolomics). We investigated whether metabolite profiles could predict the development of diabetes. Among 2,422 normoglycemic individuals followed for 12 years, 201 developed diabetes. Amino acids, amines and other polar metabolites were profiled in baseline specimens by liquid chromatography-tandem mass spectrometry (LC-MS). Cases and controls were matched for age, body mass index and fasting glucose. Five branched-chain and aromatic amino acids had highly significant associations with future diabetes: isoleucine, leucine, valine, tyrosine and phenylalanine. A combination of three amino acids predicted future diabetes (with a more than fivefold higher risk for individuals in top quartile). The results were replicated in an independent, prospective cohort. These findings underscore the potential key role of amino acid metabolism early in the pathogenesis of diabetes and suggest that amino acid profiles could aid in diabetes risk assessment.     

Wild tomato endosperm transcriptomes reveal common roles of genomic imprinting in both nuclear and cellular endosperm

Genomic imprinting is a conspicuous feature of the endosperm, a triploid tissue nurturing the embryo and synchronizing angiosperm seed development. An unknown subset of imprinted genes (IGs) is critical for successful seed development and should have highly conserved functions. Recent genome‐wide studies have found limited conservation of IGs among distantly related species, but there is a paucity of data from closely related lineages. Moreover, most studies focused on model plants with nuclear endosperm development, and comparisons with properties of IGs in cellular‐type endosperm development are lacking. Using laser‐assisted microdissection, we characterized parent‐specific expression in the cellular endosperm of three wild tomato lineages (Solanum section Lycopersicon). We identified 1025 candidate IGs and 167 with putative homologs previously identified as imprinted in distantly related taxa with nuclear‐type endosperm. Forty‐two maternally expressed genes (MEGs) and 17 paternally expressed genes (PEGs) exhibited conserved imprinting status across all three lineages, but differences in power to assess imprinted expression imply that the actual degree of conservation might be higher than that directly estimated (20.7% for PEGs and 10.4% for MEGs). Regardless, the level of shared imprinting status was higher for PEGs than for MEGs, indicating dissimilar evolutionary trajectories. Expression‐level data suggest distinct epigenetic modulation of MEGs and PEGs, and gene ontology analyses revealed MEGs and PEGs to be enriched for different functions. Importantly, our data provide evidence that MEGs and PEGs interact in modulating both gene expression and the endosperm cell cycle, and uncovered conserved cellular functions of IGs uniting taxa with cellular‐ and nuclear‐type endosperm.     

Polygenic scores,diet quality,and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts

BackgroundBoth genetic and lifestyle factors contribute to the risk of type 2 diabetes, but the extent to which there is a synergistic effect of the 2 factors is unclear. The aim of this study was to examine the joint associations of genetic risk and diet quality with incident type 2 diabetes.Methods and findingsWe analyzed data from 35,759 men and women in the United States participating in the Nurses’ Health Study (NHS) I (1986 to 2016) and II (1991 to 2017) and the Health Professionals Follow-up Study (HPFS; 1986 to 2016) with available genetic data and who did not have diabetes, cardiovascular disease, or cancer at baseline. Genetic risk was characterized using both a global polygenic score capturing overall genetic risk and pathway-specific polygenic scores denoting distinct pathophysiological mechanisms. Diet quality was assessed using the Alternate Healthy Eating Index (AHEI). Cox models were used to calculate hazard ratios (HRs) for type 2 diabetes after adjusting for potential confounders. With over 902,386 person-years of follow-up, 4,433 participants were diagnosed with type 2 diabetes. The relative risk of type 2 diabetes was 1.29 (95% confidence interval [CI] 1.25, 1.32; P < 0.001) per standard deviation (SD) increase in global polygenic score and 1.13 (1.09, 1.17; P < 0.001) per 10-unit decrease in AHEI. Irrespective of genetic risk, low diet quality, as compared to high diet quality, was associated with approximately 30% increased risk of type 2 diabetes (P_interaction = 0.69). The joint association of low diet quality and increased genetic risk was similar to the sum of the risk associated with each factor alone (P_interaction = 0.30). Limitations of this study include the self-report of diet information and possible bias resulting from inclusion of highly educated participants with available genetic data.ConclusionsThese data provide evidence for the independent associations of genetic risk and diet quality with incident type 2 diabetes and suggest that a healthy diet is associated with lower diabetes risk across all levels of genetic risk.

In an observational study of 3 cohorts in the United States, Jordi Merino, Marta Guasch-Ferré, Jun Li, and colleagues investigate the individual and combined associations between genetic risk, diet quality, and risk of type 2 diabetes.