Characterizing the genetic basis of transcriptome diversity through RNA-sequencing of 922 individuals.

Understanding the consequences of regulatory variation in the human genome remains a major challenge, with important implications for understanding gene regulation and interpreting the many disease-risk variants that fall outside of protein-coding regions. Here, we provide a direct window into the regulatory consequences of genetic variation by sequencing RNA from 922 genotyped individuals. We present a comprehensive description of the distribution of regulatory variation--by the specific expression phenotypes altered, the properties of affected genes, and the genomic characteristics of regulatory variants. We detect variants influencing expression of over ten thousand genes, and through the enhanced resolution offered by RNA-sequencing, for the first time we identify thousands of variants associated with specific phenotypes including splicing and allelic expression. Evaluating the effects of both long-range intra-chromosomal and trans (cross-chromosomal) regulation, we observe modularity in the regulatory network, with three-dimensional chromosomal configuration playing a particular role in regulatory modules within each chromosome. We also observe a significant depletion of regulatory variants affecting central and critical genes, along with a trend of reduced effect sizes as variant frequency increases, providing evidence that purifying selection and buffering have limited the deleterious impact of regulatory variation on the cell. Further, generalizing beyond observed variants, we have analyzed the genomic properties of variants associated with expression and splicing and developed a Bayesian model to predict regulatory consequences of genetic variants, applicable to the interpretation of individual genomes and disease studies. Together, these results represent a critical step toward characterizing the complete landscape of human regulatory variation.

A Commercially Available Portion-Controlled Diet Program Is More Effective for Weight Loss than a Self-Directed Diet: Results from a Randomized Clinical Trial.

OBJECTIVE: To examine changes in weight and related outcomes in response to a commercial weight loss program compared to a self-directed diet in adults with overweight or obesity. DESIGN: Participants were randomly assigned [stratified by body mass index (BMI) and age] to a commercial weight loss program (n = 38) or to a self-directed Dietary Approaches to Stop Hypertension (DASH) diet (n = 40) for a 16-week period. Daily energy intake goals were 1,500 kcal/d for men and 1,200 kcal/d for women, except for the first week of the commercial program (1,000 kcal/d). This study was registered at http://ClinicalTrials.gov (NCT03017443). PARTICIPANTS: Primarily Caucasian (71%) women (n = 61) and men (n = 17) from the greater metropolitan area of the city of Chicago, IL, USA. with a mean baseline BMI of 34.4 kg/m2, body weight of 95.7 kg, and age of 50.4 years. RESULTS: Data = mean (95% CI). At week 16, the commercial program group lost significantly more body weight [-5.9 (-7.5, -4.3) kg vs. -1.8 (-2.9, -0.8) kg; or -6.4 vs. -1.8% of initial body weight, respectively], fat mass [-4.4 (-5.7, -3.1) kg vs. -1.2 (-2.1, -0.4) kg] and total body circumference (chest + waist + hip + upper arm + thigh) [-16.9 (-21.5, -12.3) cm vs. -5.8 (-9.0, -2.6) cm] (p < 0.01 for all). Additionally, more participants in the commercial program group lost a clinically meaningful amount of weight, defined as ≥5% of initial body weight, at week 16 (58% vs. 13%, p < 0.001). CONCLUSION: The commercial program resulted in greater weight loss and improvements in body composition/anthropometric parameters compared to a self-directed DASH diet over a 16-week period. Some important limitations were that no objective measurements of dietary intake or physical activity were collected to potentially ascertain the independent or combined effects of these components on weight loss (or lack thereof). Additionally, future research is warranted in order to understand the effects of this program, and similar programs, on longer term changes in body weight, in particular weight loss maintenance, as weight regain is common following the cessation of a structured weight loss intervention.

Characterization of the Asian Citrus Psyllid Transcriptome.

The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae) is a vector for the causative agents of Huanglongbing, which threatens citrus production worldwide. This study reports and discusses the first D. citri transcriptomes, encompassing the three main life stages of D. citri, egg, nymph and adult. The transcriptomes were annotated using Gene Ontology (GO) and insecticide-related genes within each life stage were identified to aid the development of future D. citri insecticides. Transcriptome assemblies and other sequence data are available for download at the International Asian Citrus Psyllid Genome Consortium website [http://psyllid.org/download] and at NCBI [http://www.ncbi.nlm.nih.gov/bioproject/29447].