Design, methods, and participant characteristics of the Impact of Personal Genomics (PGen) Study, a prospective cohort study of direct-to-consumer personal genomic testing customers

Designed in collaboration with 23andMe and Pathway Genomics, the Impact of Personal Genomics (PGen) Study serves as a model for academic-industry partnership and provides a longitudinal dataset for studying psychosocial, behavioral, and health outcomes related to direct-to-consumer personal genomic testing (PGT). Web-based surveys administered at three time points, and linked to individual-level PGT results, provide data on 1,464 PGT customers, of which 71% completed each follow-up survey and 64% completed all three surveys. The cohort includes 15.7% individuals of non-white ethnicity, and encompasses a range of income, education, and health levels. Over 90% of participants agreed to re-contact for future research. Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0096-0) contains supplementary material, which is available to authorized users

ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing

In clinical exome and genome sequencing, there is potential for the recognition and reporting of incidental or secondary findings unrelated to the indication for ordering the sequencing but of medical value for patient care. The American College of Medical Genetics and Genomics (ACMG) recently published a policy statement on clinical sequencing, which emphasized the importance of disclosing the possibility of such results in pretest patient discussions, clinical testing, and reporting of results. The ACMG appointed a Working Group on Incidental Findings in Clinical Exome and Genome Sequencing to make recommendations about responsible management of incidental findings when patients undergo exome or genome sequencing. This Working Group conducted a year-long consensus process, including review by outside experts, and produced recommendations that have been approved by the ACMG Board. Specific and detailed recommendations, and the background and rationale for these recommendations, are described herein. We recommend that laboratories performing clinical sequencing seek and report mutations of the specified classes or types in the genes listed here. This evaluation and reporting should be performed for all clinical germline (constitutional) exome and genome sequencing, including the ‘normal’ of tumor-normal subtractive analyses in all subjects, irrespective of age, but excluding fetal samples. We recognize that there are insufficient data on clinical utility to fully support these recommendations and we encourage the creation of an ongoing process for updating these recommendations at least annually as further data are collected

Diet and exercise changes following direct-to-consumer personal genomic testing

Background: The impacts of direct-to-consumer personal genomic testing (PGT) on health behaviors such as diet and exercise are poorly understood. Our investigation aimed to evaluate diet and exercise changes following PGT and to determine if changes were associated with genetic test results obtained from PGT. Methods: Customers of 23andMe and Pathway Genomics completed a web-based survey prior to receiving PGT results (baseline) and 6 months post-results. Fruit and vegetable intake (servings/day), and light, vigorous and strength exercise frequency (days/week) were assessed. Changes in diet and exercise were examined using paired t-tests and linear regressions. Additional analyses examined whether outcomes differed by baseline self-reported health (SRH) or content of PGT results. Results: Longitudinal data were available for 1,002 participants. Significant increases were observed for vegetable intake (mean Δ = 0.11 (95% CI = 0.05, 0.17), p = 0.0003) and strength exercise (Δ = 0.14 (0.03, 0.25), p = 0.0153). When stratified by SRH, significant increases were observed for all outcomes among lower SRH participants: fruit intake, Δ = 0.11 (0.02, 0.21), p = 0.0148; vegetable intake, Δ = 0.16 (0.07, 0.25), p = 0.0005; light exercise, Δ = 0.25 (0.03, 0.47), p = 0.0263; vigorous exercise, Δ = 0.23 (0.06, 0.41), p = 0.0097; strength exercise, Δ = 0.19 (0.01, 0.37), p = 0.0369. A significant change among higher SRH participants was only observed for light exercise, and in the opposite direction: Δ = -0.2468 (-0.06, -0.44), p = 0.0111. Genetic results were not consistently associated with any diet or exercise changes. Conclusions: The experience of PGT was associated with modest, mostly positive changes in diet and exercise. Associations were independent of genetic results from PGT

Brain-behaviour modes of covariation in healthy and clinically depressed young people

Abstract: Understanding how variations in dimensions of psychometrics, IQ and demographics relate to changes in brain connectivity during the critical developmental period of adolescence and early adulthood is a major challenge. This has particular relevance for mental health disorders where a failure to understand these links might hinder the development of better diagnostic approaches and therapeutics. Here, we investigated this question in 306 adolescents and young adults (14–24 y, 25 clinically depressed) using a multivariate statistical framework, based on canonical correlation analysis (CCA). By linking individual functional brain connectivity profiles to self-report questionnaires, IQ and demographic data we identified two distinct modes of covariation. The first mode mapped onto an externalization/internalization axis and showed a strong association with sex. The second mode mapped onto a well-being/distress axis independent of sex. Interestingly, both modes showed an association with age. Crucially, the changes in functional brain connectivity associated with changes in these phenotypes showed marked developmental effects. The findings point to a role for the default mode, frontoparietal and limbic networks in psychopathology and depression

Exploring concordance and discordance for return of incidental findings from clinical sequencing

To explore specific conditions and types of genetic variants that specialists in genetics recommend should be returned as incidental findings in clinical sequencing

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Development of a Fluorescence Polarization-Based Diagnostic Assay for Equine Infectious Anemia Virus

The control of equine infectious anemia virus (EIAV) infections of horses has been over the past 20 years based primarily on the identification and elimination of seropositive horses, predominantly by a standardized agar gel immunodiffusion (AGID) assay in centralized reference laboratories. This screening for EIAV-seropositive horses has been to date hindered by the lack of a rapid diagnostic format that can be easily employed in the field. We describe here the development of a rapid solution-phase assay for the presence of serum antibodies to EIAV based on fluorescence polarization (FP) (patent pending). Peptides derived from antigenic regions of EIAV core and envelope proteins were initially screened for their utility as probes in an FP assay to select the best peptide antigen candidates. The FP assay was optimized to detect the presence of EIAV-specific antibodies by a change in the FP of a fluorescein-labeled immunoreactive peptide diagnostic antigen. The most sensitive and specific peptide probe was a peptide corresponding to the immunodominant region of the EIAV transmembrane protein, gp45. This probe was tested for its reactivity in the optimized FP assay with 151 AGID-positive horse sera and 106 AGID-negative serum samples. The results of these studies demonstrated that the FP assay reactivity correlated with reported AGID results in 106 of 106 negative serum samples (100% specificity) and in 135 of 151 positive serum samples (89.4% sensitivity). The FP assay was also found to have a very low background reactivity and to readily detect antibodies produced early in infection (≤3 weeks postinfection). The developed EIAV FP assay is rapid (5 to 20 min) and simple to perform and is equally suitable for use both in the field and in the diagnostic laboratory, thus providing the basis of an improved commercial diagnostic assay for EIAV infection of horses

In the Early Postpartum Period, Parents are Interested in Newborn Genomic Testing

Purpose We surveyed parents to ascertain interest in newborn genomic testing and determine whether these queries would provoke refusal of conventional newborn screening (NBS). Methods: After brief genetics orientation, parents rated their interest in receiving genomic testing for their healthy newborn on a 5-point Likert scale and answered questions about demographics and health history. We used logistic regression to explore factors associated with interest in genomic testing and tracked any subsequent rejection of NBS. Results: We queried 514 parents within 48 hours after birth while still in the hospital (mean age (sd) 32.7 (6.4) years, 65.2% female, 61.2% white, 79.3% married). Parents reported being not at all (6.4%), a little (10.9%), somewhat (36.6%), very (28.0%) or extremely (18.1%) interested in genomic testing for their newborns. None refused conventional NBS. Married participants and those with health concerns about their infant were less interested in newborn genomic testing (p=0.012 and p=0.030, respectively). Mothers’ and fathers’ degree of interest was discordant (≥ 2 categories different) in 24.4% of couples. Conclusions: Interest in newborn genomic testing was high among parents of healthy newborns and the majority of couples had similar levels of interest. Surveying parents about genomic sequencing did not prompt rejection of NBS

Clinical genetic counseling and translation considerations for polygenic scores in personalized risk assessments: A Practice Resource from the National Society of Genetic Counselors

Polygenic scores (PGS) are primed for use in personalized risk assessments for common, complex conditions and population health screening. Although there is growing evidence supporting the clinical validity of these scores in certain diseases, presently, there is no consensus on best practices for constructing PGS or demonstrated clinical utility in practice. Despite these evidence gaps, individuals can access their PGS information through commercial entities, research programs, and clinical programs. This prompts the immediate need for educational resources for clinicians encountering PGS information in clinical practice. This practice resource is intended to increase genetic counselors\u27 and other healthcare providers\u27 understanding and comfort with PGS used in personalized risk assessments. Drawing on best practices in clinical genomics, we discuss the unique considerations for polygenic-based (1) testing, (2) clinical genetic counseling, and (3) translation to population health services. This practice resource outlines the emerging uses of PGS, as well as the critical limitations of this technology that need to be addressed before wide-scale implementation