Sharon Aufox

Clinical implementation of noninvasive prenatal testing among maternal fetal medicine specialists.

To assess the clinical implementation of non‐invasive prenatal testing (NIPT) among maternal‐fetal medicine (MFM) specialists.

Practical Guidance on Informed Consent for Pediatric Participants in a Biorepository

In the decade since the Human Genome Project was completed, the knowledge and technologies that this project enabled have led to a remarkable evolution in the way biorepositories are designed and operate. Early biobanks were often designed to facilitate the study of a single condition, while biobanks established in the last decade have more frequently been created with a broader research mission in mind.1 Accompanying this transition have come other changes in biobank practices, including the generation and storage of genome-scale sequencing data, frequent sharing of biosamples and data, pooling of resources among sample collections, and increased interest in returning genetic research results to sample donors. As biorepository practices have become more complex, the task of developing appropriate informed consent practices has become more challenging. There are at least three reasons for this. First, the regulations that govern research with human subjects in the U.S., known collectively as the Common Rule, were written at a time when many of the recent innovations in biobank practices were not anticipated. Second, Institutional Review Boards (IRBs) are tasked with evaluating whether research studies meet both federal regulations and local standards for acceptable research, yet IRB members are often unfamiliar with the complexities of biobanks. Third, it can be quite challenging to explain these practices in informed consent documents in a way that is easy for potential research participants to read and understand. Because of these challenges, several groups have developed practical guidance on informed consent. For example, the website of the National Human Genome Research Institute (NHGRI), Genome.gov, provides model informed consent language developed for genomic research studies, including biobanks.2 The NHGRI website also hosts a white paper developed by our group, the Electronic Medical Records and Genomics (eMERGE) Network.3 This document provides model language for informed consent documents that investigators may adapt for their own biorepository projects. One limitation of these resources, however, is their focus on adult research participants. There are currently no similar resources that address the unique issues that arise for biorepositories that aim to collect samples from pediatric participants. This is an important gap in the literature, since the challenges associated with biobanking are magnified in the setting of pediatric research. The ability of children to engage in informed decision-making varies according to their developmental level, so parental permission is usually required for pediatric research participation. However, a parent’s permission for a child to participate in research is quite different from an adult’s consent for his or her own research participation. A parent’s decision must account for the best interests of the child, while at the same time balancing the future autonomy of the child and the needs of the family. To be sure, there is a robust literature on these unique issues that arise in pediatric research,4,5 including a number of helpful papers that address pediatric biorepositories specifically.6,7 However, it can be difficult for investigators and IRB members to distill these empirical and analytical resources into concrete practices related to the informed consent process. This document is designed to address that need. Writing on behalf of the Consent, Education, Regulation, and Consultation (CERC) workgroup of the eMERGE Network, we provide pediatric-focused guidance for investigators and IRB members working in the U.S regulatory context on pediatric informed consent practices for biorepositories.

Penetrance of Hemochromatosis in HFE Genotypes Resulting in p.Cys282Tyr and p.[Cys282Tyr];[His63Asp] in the eMERGE Network

Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder associated with pathogenic HFE variants, most commonly those resulting in p.Cys282Tyr and p.His63Asp. Recommendations on returning incidental findings of HFE variants in individuals undergoing genome-scale sequencing should be informed by penetrance estimates of HH in unselected samples. We used the eMERGE Network, a multicenter cohort with genotype data linked to electronic medical records, to estimate the diagnostic rate and clinical penetrance of HH in 98 individuals homozygous for the variant coding for HFE p.Cys282Tyr and 397 compound heterozygotes with variants resulting in p.[His63Asp];[Cys282Tyr]. The diagnostic rate of HH in males was 24.4% for p.Cys282Tyr homozygotes and 3.5% for compound heterozygotes (p < 0.001); in females, it was 14.0% for p.Cys282Tyr homozygotes and 2.3% for compound heterozygotes (p < 0.001). Only males showed differences across genotypes in transferrin saturation levels (100% of homozygotes versus 37.5% of compound heterozygotes with transferrin saturation > 50%; p = 0.003), serum ferritin levels (77.8% versus 33.3% with serum ferritin > 300 ng/ml; p = 0.006), and diabetes (44.7% versus 28.0%; p = 0.03). No differences were found in the prevalence of heart disease, arthritis, or liver disease, except for the rate of liver biopsy (10.9% versus 1.8% [p = 0.013] in males; 9.1% versus 2% [p = 0.035] in females). Given the higher rate of HH diagnosis than in prior studies, the high penetrance of iron overload, and the frequency of at-risk genotypes, in addition to other suggested actionable adult-onset genetic conditions, opportunistic screening should be considered for p.[Cys282Tyr];[Cys282Tyr] individuals with existing genomic data.

Biobanking: The Melding of Research with Clinical Care.

The number of biobanks around the world has increased dramatically, owing in part, to the need for researchers to have access to large numbers of samples for genomic research. Policies for enrolling participants, returning research results and obtaining samples and data can have a far reaching impact on the type of research that can be performed with each biobank. Research using biobank samples includes studies of the impact of environmental and other risk exposures on health, understanding genetic risks for common disease, identification of biomarkers in disease progression and prognosis, and implementation of personalized medicine projects. This research has been instrumental in the progress of genetic and genomic research and translational medicine. This article will highlight some of the controversies and recent research associated with biobanking over the past year.

Factors Associated With Long-Term Weight Loss Following Bariatric Surgery Using 2 Methods for Repeated Measures Analysis

We used electronic health record data from 162 patients enrolled in the NUgene Project (2002-2013) to determine demographic factors associated with long-term (from 1 to up to 9.5 (mean = 5.6) years) weight loss following Roux-en-Y gastric bypass surgery. Ninety-nine (61.1%) patients self-reported white, and 63 (38.9%) self-reported black, mixed, or missing race. The average percent weight loss was -33.4% (standard deviation, 9.3) at 1 year after surgery and -30.7% (standard deviation, 12.5) at the last follow-up point. We used linear mixed and semiparametric trajectory models to test the association of surgical and demographic factors (height, surgery age, surgery weight, surgery body mass index, marital status, sex, educational level, site, International Classification of Diseases code, Current Procedural Terminology code, Hispanic ethnicity, and self-reported race) with long-term percent weight loss and pattern of weight loss. We found that black, mixed, and missing races (combined) in comparison with white race were associated with a decreased percent weight loss of -4.31% (95% confidence interval: -7.30, -1.32) and were less likely to have higher and sustained percent weight loss (P = 0.04). We also found that less obese patients were less likely to have higher and sustained percent weight loss (P = 0.01). These findings may be helpful to patients in setting expectations after weight loss surgery.

The genetics of ovarian cancer: An assessment of current screening protocols and recommendations for counseling families at risk

Although the need for effective ovarian cancer screening is apparent, a highly sensitive and specific screening methodology has yet to be elucidated. 42-44 Given that there are more than 43 million women in the United States older than 45 years of age and that the average cost of a pelvic sonogram is

Ethical Considerations Related to Return of Results from Genomic Medicine Projects: The eMERGE Network (Phase III) Experience

275 (and

Conducting a large, multi-site survey about patients' views on broad consent: challenges and solutions

45 for CA125 screening), the screening of this population is estimated to increase health care costs by

Great expectations: patient perspectives and anticipated utility of non-diagnostic genomic-sequencing results

14 billion per year. 45 The additional cost of BRCA1 screening varies according to the level of diagnostic effort required to establish BRCA1 gene mutations in a particular family and ranges from

What People Want to Know About Their Genes: A Critical Review of the Literature on Large-Scale Genome Sequencing Studies

295 to