Genetic and environmental influences on eating behavior - a study of twin pairs reared apart or reared together

This study examined the relative influence of genetic versus environmental factors on specific aspects of eating behavior. Adult monozygotic twins (22 pairs and 3 singleton reared apart, 38 pairs and 9 singleton reared together, age 18-76 years, BMI 17-43 kg/m2) completed the Three Factor Eating Questionnaire. Genetic and environmental variance components were determined for the three eating behavior constructs and their subscales using model-fitting univariate and multivariate analyses. Unique environmental factors had a substantial influence on all eating behavior variables (explaining 45-71% of variance), and most strongly influenced external locus for hunger and strategic dieting behavior of restraint (explaining 71% and 69% of variance, respectively). Genetic factors had a statistically significant influence on only 4 variables: restraint, emotional susceptibility to disinhibition, situational susceptibility to disinhibition, and internal locus for hunger (heritabilities were 52%, 55%, 38% and 50%, respectively). Common environmental factors did not statistically significantly influence any variable assessed in this study. In addition, multivariate analyses showed that disinhibition and hunger share a common influence, while restraint appears to be a distinct construct. These findings suggest that the majority of variation in eating behavior variables is associated with unique environmental factors, and highlights the importance of the environment in facilitating specific eating behaviors that may promote excess weight gain.R01 AR046124 - NIAMS NIH HHS; R01 MH065322 - NIMH NIH HHS; T32 HL069772 - NHLBI NIH HHS; R37 DA018673 - NIDA NIH HHS; R01 DK073321 - NIDDK NIH HHS; R01 DA018673 - NIDA NIH HH

Letters of Heroines

There are moments in life when making progress feels arduous, goals seem unattainable, and attempts at resolution prove only to create more conflict. This contemporary jazz piece explores the physical and emotional connotations of the idiom taking “one step forward and two steps back.” In a physical sense, the movement depicts progress followed by relapse. In a figurative sense, dancers explore emotions of frustration, struggling to break down the barriers that they encounter. This piece serves as a metaphor for persistence in the face of obstacles

The fibrillogenic L178H variant of apolipoprotein A-I forms helical fibrils.

A number of amyloidogenic variants of apolipoprotein A-I (apoA-I) have been discovered but most have not been analyzed. Previously, we showed that the G26R mutation of apoA-I leads to increased β-strand structure, increased N-terminal protease susceptibility and increased fibril formation after several days of incubation. In vivo, this and other variants mutated in the N-terminal domain (residues 26 to ~90) lead to renal and hepatic accumulation. In contrast, several mutations identified within residues 170 to 178 lead to cardiac, laryngeal, and cutaneous protein deposit. Here, we describe the structural changes in the fibrillogenic variant L178H. Like G26R, the initial structure of the protein exhibits altered tertiary conformation relative to WT protein along with decreased stability and an altered lipid binding profile. However, in contrast to G26R, L178H undergoes an increase in helical structure upon incubation at 37oC with a t1/2 of about 12 days. Upon prolonged incubation the L178H mutant forms fibrils of a diameter of 10 nm that ranges in length from 30 to 120 nm. JLR These results show that apoA-I, known for its dynamic properties, has the ability to form multiple fibrillar conformations, which may play a role in the tissue-specific deposition of the individual variants

Racial/Ethnic and Socioeconomic Disparities in Endocrine Therapy Adherence in Breast Cancer: A Systematic Review

We examined the current literature to understand factors that influence endocrine therapy (ET) adherence among racial/ethnic and socioeconomic subpopulations of breast cancer patients. We searched PubMed and PsycINFO databases for studies from January 1, 1978, to June 20, 2014, and January 1, 1991, to June 20, 2014, respectively, and hand-searched articles from relevant literature reviews. We abstracted and synthesized results within a social ecological framework

Effect of body composition methodology on heritability estimation of body fatness

Heritability estimates of human body fatness vary widely and the contribution of body composition methodology to this variability is unknown. The effect of body composition methodology on estimations of genetic and environmental contributions to body fatness variation was examined in 78 adult male and female monozygotic twin pairs reared apart or together. Body composition was assessed by six methods - body mass index (BMI), dual energy x-ray absorptiometry (DXA), underwater weighing (UWW), total body water (TBW), bioelectric impedance (BIA), and skinfold thickness. Body fatness was expressed as percent body fat, fat mass, and fat mass/height2 to assess the effect of body fatness expression on heritability estimates. Model-fitting multivariate analyses were used to assess the genetic and environmental components of variance. Mean BMI was 24.5 kg/m2 (range of 17.8-43.4 kg/m2). There was a significant effect of body composition methodology (p<0.001) on heritability estimates, with UWW giving the highest estimate (69%) and BIA giving the lowest estimate (47%) for fat mass/height2. Expression of body fatness as percent body fat resulted in significantly higher heritability estimates (on average 10.3% higher) compared to expression as fat mass/height2 (p=0.015). DXA and TBW methods expressing body fatness as fat mass/height2 gave the least biased heritability assessments, based on the small contribution of specific genetic factors to their genetic variance. A model combining DXA and TBW methods resulted in a relatively low FM/ht2 heritability estimate of 60%, and significant contributions of common and unique environmental factors (22% and 18%, respectively). The body fatness heritability estimate of 60% indicates a smaller contribution of genetic variance to total variance than many previous studies using less powerful research designs have indicated. The results also highlight the importance of environmental factors and possibly genotype by environmental interactions in the etiology of weight gain and the obesity epidemic.R01 AR046124 - NIAMS NIH HHS; R01 MH065322 - NIMH NIH HHS; T32 HL069772 - NHLBI NIH HHS; R21 DK078867 - NIDDK NIH HHS; R37 DA018673 - NIDA NIH HHS; R01 DK076092 - NIDDK NIH HHS; R01 DK079003 - NIDDK NIH HHS; F32 DK009747 - NIDDK NIH HHS; R01 DA018673 - NIDA NIH HH

Patient-Centered Communication for Discussing Oncotype DX Testing

Oncotype DX testing (ODX), a tumor gene expression test, may improve breast cancer care, however communicating results remains challenging. We identified patient-centered communication strategies/gaps for discussing ODX results. We applied a patient-centered communication framework to analyze qualitative interviews with oncologists about how they communicate about ODX with patients, using template analysis in Atlas.ti. Overall, providers discussed four patient-centered communication domains: exchanging information, assessing uncertainty, making decisions and cross-cutting themes. Providers did not report discussing emotional aspects of managing uncertainty, assessing decision-making preferences, and evaluating decisions. A patient-centered approach may be a model for communicating about tumor gene expression tests

Oncology providers' perspectives on endocrine therapy prescribing and management.

Adjuvant endocrine therapy (ET) can reduce the risk of recurrence among females with hormone receptor-positive breast cancer. Overall, initiation and adherence to ET are suboptimal, though reasons are not well described. The study's objective was to better understand ET decision making, prescribing, and patient management from oncology providers' perspectives. Using purposive sampling, we recruited oncology providers who saw five or more breast cancer patients per week (n=20). We conducted 30-45-minute telephone interviews, using a semistructured guide to elicit perspectives on ET use. We used thematic content analysis to systematically identify categories of meaning and double-coded transcripts using Atlas.ti. Providers recommend ET to all eligible patients except those with contraindications or other risk factors. Providers base their ET prescribing decisions on the patient's menopausal status, side effects, and comorbidities. ET is typically discussed multiple times: at the onset of breast cancer treatment and in more detail after other treatment completion. Providers felt that the associated recurrence risk reduction is the most compelling argument for patients during ET decision making. While providers rarely perceived noninitiation as a problem, nonadherence was prevalent, often due to unresolvable side effects. From the clinicians' perspectives, side effects from ET are the dominant factor in nonadherence. Efforts to improve adherence should focus on strategies to minimize side effects and ensure clinicians and patients are well informed regarding optimal side effect management. This finding has important implications for novel endocrine regimens that offer improved outcomes through longer duration or more intensive therapy

Allele-specific binding of ZFP57 in the epigenetic regulation of imprinted and non-imprinted monoallelic expression.

BACKGROUND: Selective maintenance of genomic epigenetic imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary for maintaining the DNA methylation memory at multiple imprinting control regions in early mouse embryos and embryonic stem (ES) cells. Maternal-zygotic deletion of ZFP57 in mice presents a highly penetrant phenotype with no animals surviving to birth. Additionally, several cases of human transient neonatal diabetes are associated with somatic mutations in the ZFP57 coding sequence. RESULTS: Here, we comprehensively map sequence-specific ZFP57 binding sites in an allele-specific manner using hybrid ES cell lines from reciprocal crosses between C57BL/6J and Cast/EiJ mice, assigning allele specificity to approximately two-thirds of all binding sites. While half of these are biallelic and include endogenous retrovirus (ERV) targets, the rest show monoallelic binding based either on parental origin or on genetic background of the allele. Parental-origin allele-specific binding is methylation-dependent and maps only to imprinting control differentially methylated regions (DMRs) established in the germline. We identify a novel imprinted gene, Fkbp6, which has a critical function in mouse male germ cell development. Genetic background-specific sequence differences also influence ZFP57 binding, as genetic variation that disrupts the consensus binding motif and its methylation is often associated with monoallelic expression of neighboring genes. CONCLUSIONS: The work described here uncovers further roles for ZFP57-mediated regulation of genomic imprinting and identifies a novel mechanism for genetically determined monoallelic gene expression.The authors acknowledge support from the Wellcome Trust, BBSRC, and EU FP7 Initial Training Networks INGENIUM (Marie-Curie Action 290123) and EpiHealthNet (Marie Curie Action 317146).This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13059-015-0672-