Size of the direct-to-consumer genomic testing market

There has been enormous interest in the recent development of consumer genomics services, but very little is known about their impact. Using publicly available information, we estimate that the market for genetic susceptibility tests for complex diseases is much smaller than previously suggested, and hence consider that regulation through restrictive statutory legislation may be excessive.     

Adopting genetics: motivations and outcomes of personal genomic testing in adult adoptees

PurposeAmerican adult adoptees may possess limited information about their biological families and turn to direct-to-consumer personal genomic testing (PGT) for genealogical and medical information. We investigated the motivations and outcomes of adoptees undergoing PGT using data from the Impact of Personal Genomics (PGen) Study.MethodsThe PGen Study surveyed new 23andMe and Pathway Genomics customers before and 6 months after receiving PGT results. Exploratory analyses compared adoptees’ and nonadoptees’ PGT attitudes, expectations, and experiences. We evaluated the association of adoption status with motivations for testing and postdisclosure actions using logistic regression models.ResultsOf 1,607 participants, 80 (5%) were adopted. As compared with nonadoptees, adoptees were more likely to cite limited knowledge of family health history (OR = 10.1; 95% CI = 5.7–19.5) and the opportunity to learn genetic disease risks (OR = 2.7; 95% CI = 1.6–4.8) as strong motivations for PGT. Of 922 participants who completed 6-month follow-up, there was no significant association between adoption status and PGT-motivated health-care utilization or health-behavior change.ConclusionPGT allows adoptees to gain otherwise inaccessible information about their genetic disease risks and ancestry, helping them to fill the void of an incomplete family health history.Genet Med 18 9, 924–932.     

Impact of direct-to-consumer genetic testing on Australian clinical genetics services

The increasing popularity of direct-to-consumer genetic testing (DTCGT) is thought to be creating a burden on clinical genetic services worldwide. However, no Australian studies have collected recent evidence regarding this impact. We surveyed Australian clinical genetics services about DTCGT-related referrals over the past 10 years. Eleven publicly-funded services reported over 100 DTCGT-related referrals. Most (83%) involved general practitioners seeking interpretation of DTCGT results. More than 30% involved imputed risk estimates from third-party software tools. Services reported low validation rates for DTCGT results (<10%), and variable procedures for managing DTCGT referrals, with most (8/11) lacking specific procedures. Our study helps quantify the impact of DTCGT on clinical genetics services, and highlights the impact of imputed risk estimates.     

Multigenic condition risk assessment in direct-to-consumer genomic services

PurposeGene carrier status and pharmacogenomic data may be detectable from single nucleotide polymorphisms (SNPs), but SNP-based research concerning multigenic common disease such as diabetes, cancers, and cardiovascular disease is an emerging field. The many SNPs and loci that may relate to common disease have not yet been comprehensively identified and understood scientifically. In the interim, direct-to-consumer (DTC) genomic companies have forged ahead in developing composite risk interpretations for multigenic conditions. It is useful to understand how variance in risk interpretation may arise.MethodsA comprehensive study was conducted to analyze the 213 conditions covered by the 5 identifiable genome-wide DTC genomic companies, and the total SNPs (401) and loci (224) assessed in the 20 common disease conditions with the greatest overlapping coverage.ResultsVariance in multigenic condition risk interpretation can be explained by differences in the average lifetime risk assigned to similar underlying populations, the loci and SNPs selected for analysis, and the quantitative risk assignment methodologies used by DTC genomic companies.ConclusionAt present, multigenic condition analysis is a complicated process. DTC genomic companies have made laudable efforts to deliver risk predictions, but greater consistency is needed for the long-term validity, utility, and credibility of the sector.     

Legislation on direct-to-consumer genetic testing in seven European countries

An increasing number of private companies are now offering direct-to-consumer (DTC) genetic testing services. Although a lot of attention has been devoted to the regulatory framework of DTC genetic testing services in the USA, only limited information about the regulatory framework in Europe is available. We will report on the situation with regard to the national legislation on DTC genetic testing in seven European countries (Belgium, the Netherlands, Switzerland, Portugal, France, Germany, the United Kingdom). The paper will address whether these countries have legislation that specifically address the issue of DTC genetic testing or have relevant laws that is pertinent to the regulatory control of these services in their countries. The findings show that France, Germany, Portugal and Switzerland have specific legislation that defines that genetic tests can only be carried out by a medical doctor after the provision of sufficient information concerning the nature, meaning and consequences of the genetic test and after the consent of the person concerned. In the Netherlands, some DTC genetic tests could fall under legislation that provides the Minister the right to refuse to provide a license to operate if a test is scientifically unsound, not in accordance with the professional medical practice standards or if the expected benefit is not in balance with the (potential) health risks. Belgium and the United Kingdom allow the provision of DTC genetic tests.     

The impact of direct-to-consumer marketing of cancer genetic testing on women according to their genetic risk

PurposeTo assess the impact of direct-to-consumer marketing for genetic testing among women of varying genetic risk for breast and ovarian cancer.MethodsTelephone surveys were conducted with 315 women in Denver, Colorado, one target audience for the Myriad BRACAnalysis ad campaign. Genetic risk was determined from personal and family history and grouped by probability of having a BRCA1/2 mutation (low <5%, moderate 5–<10%, high ≥10%).ResultsHigh-risk women were more knowledgeable about BRACAnalysis and more likely to recall the media ads than were low-risk women (60 vs. 39%, P < 0.01). After seeing the ads, about 40% of women were more interested in testing and about 10% expressed increased worry about developing breast or ovarian cancer. Women across all risk groups overstated the benefits and appropriateness of testing. An equal percentage of high- and low-risk women (51 and 60%) felt that they would benefit from genetic testing.ConclusionThe campaign effectively reached a large audience. Concern about breast cancer was not appreciably increased. A large percentage of low-risk women (not candidates for testing) expressed interest in testing, suggesting the campaign was too broad. A campaign targeted at high-risk women, who may benefit from testing might be preferred.     

Recent advances in array comparative genomic hybridization technologies and their applications in human genetics

Array comparative genomic hybridization (array CGH) is a method used to detect segmental DNA copy number alterations. Recently, advances in this technology have enabled high-resolution examination for identifying genetic alterations and copy number variations on a genome-wide scale. This review describes the current genomic array platforms and CGH methodologies, highlights their applications for studying cancer genetics, constitutional disease and human variation, and discusses visualization and analytical software programs for computational interpretation of array CGH data.     

The time-consuming demands of the practice of medical genetics in the era of advanced genomic testing

PurposeClinical genetics services are time- and labor-intensive. With increasing pressure for cost-effective medical care, the means of providing medical genetics services need to be evaluated in the current era of new genomic technologies.MethodsAn anonymous online survey regarding activities linked to medical genetics practice was administered to an international cohort of professionals.ResultsAmong 151 responses, the reported average time required for pediatric, oncogenetic, pregnancy with a malformed fetus, and preamniocentesis counseling sessions was 48, 37, 40, and 18 min, respectively. The time required to prepare a summary letter followed a similar pattern. Professionals with less experience needed more time for specific activities. The time required for the total workup of a pediatric patient ranged from 1 h and 48 min to 4 h, most of which was associated with indirect activities. Professionals performing one type of consultation (74% pediatric geneticists) perform fewer consultations per week. Respondents’ narrative comments reflected the complexity of the work and challenges faced.ConclusionClinical genetics is a time-consuming profession with increased demands related to advanced genetic and genomic testing. Further consideration is required to determine how to adapt these changes to the demands of cost-effectiveness without compromising the quality of patient care.     

Public awareness and use of direct-to-consumer personal genomic tests from four state population-based surveys,and implications for clinical and public health practice

PurposeDirect-to-consumer personal genomic tests are widely available, but population-based data are limited on awareness and use of these tests among the general public in the United States.MethodsWe assessed awareness and use of direct-to-consumer personal genomic tests in Connecticut, Michigan, Oregon, and Utah using the 2009 Behavioral Risk Factor Surveillance System and compared the state results to the 2008 national HealthStyles survey results.ResultsAwareness was the highest in Oregon (29.1%) and the lowest in Michigan (15.8%). Factors associated with awareness across all states and nationally were higher education, higher income, and increasing age, except among those 75 years or older. Less than 1% of respondents had used the tests, with about one-half to three-quarters of those sharing the results with a health-care provider.ConclusionsAwareness of direct-to-consumer genetic tests is greater in this study as compared with a related study conducted in 2006, whereas use is similarly low in both studies. The few respondents who reported using the tests often reported sharing their results with their health-care provider, indicating an important opportunity for health-care providers to offer patient education regarding these tests. Public health agencies have important roles in surveillance, education, and policy development on direct-to-consumer genomic tests.Genet Med 2012:14(10):860–867     

Perceptions of genetic counseling services in direct‐to‐consumer personal genomic testing

To describe consumers' perceptions of genetic counseling services in the context of direct‐to‐consumer personal genomic testing is the purpose of this research. Utilizing data from the Scripps Genomic Health Initiative, we assessed direct‐to‐consumer genomic test consumers' utilization and perceptions of genetic counseling services. At long‐term follow‐up, approximately 14 months post‐testing, participants were asked to respond to several items gauging their interactions, if any, with a Navigenics genetic counselor, and their perceptions of those interactions. Out of 1325 individuals who completed long‐term follow‐up, 187 (14.1%) indicated that they had spoken with a genetic counselor. The most commonly given reason for not utilizing the counseling service was a lack of need due to the perception of already understanding one's results (55.6%). The most common reasons for utilizing the service included wanting to take advantage of a free service (43.9%) and wanting more information on risk calculations (42.2%). Among those who utilized the service, a large fraction reported that counseling improved their understanding of their results (54.5%) and genetics in general (43.9%). A relatively small proportion of participants utilized genetic counseling after direct‐to‐consumer personal genomic testing. Among those individuals who did utilize the service, however, a large fraction perceived it to be informative, and thus presumably beneficial.     

Possible steroid withdrawal syndrome following short Synacthen test--a personal report

Symptoms not attributable either to disease rebound or to adrenal suppression have been reported both in patients receiving steroids when long-term therapy has been stopped and in normal volunteers after single oral doses of prednisolone or intravenous equivalents. This so-called steroid withdrawal syndrome remains poorly understood. It has not previously been reported following exposure to increased levels of endogenous steroids after diagnostic administration of synthetic adrenocorticotrophic hormone (ACTH). The author's personal experience of an apparent steroid withdrawal reaction following a short Synacthen test is described. It is suggested that as yet unidentified individual factors must play a role in determining whether steroid withdrawal symptoms occur. Closer observation of other subjects after the Synacthen test might reveal other instances of steroid withdrawal symptomatology following this common diagnostic procedure.     

Medical genetics and genomic medicine in Japan

Since 1961, all Japanese citizens have belonged to one of the available medical care insurance systems. This “universal care” system has contributed to the maintenance of health: the life expectancy at birth was 84 years in 2016, and the infant mortality rate (the number of infants dying before reaching 1 year of age) was 2.0 per 1,000 live births, which is one of the lowest rates in the world. The Japanese government initiated the National Program on Rare and Intractable Diseases in 1972. This program has promoted research and expanded support for patients with rare and intractable diseases. Registered patients are eligible for a subsidy scheme that helps to cover medical care costs. Among the 331 diseases that are currently included in this program, more than half of the diseases are Mendelian disorders. The National Program on Rare and Intractable Diseases has fostered research in medical genetics in Japan and many causative genes for Mendelian diseases have been identified by Japanese geneticists. Recently, the Japanese government has determined to support several genomic medicine initiatives including the undiagnosed disease program (Initiative on Rare and Undiagnosed Diseases) and pathogenic variant databases.     

Capturing the clinical utility of genomic testing: medical recommendations following pediatric microarray

Interpretation of pediatric chromosome microarray (CMA) results presents diagnostic and medical management challenges. Understanding management practices triggered by CMA will inform clinical utility and resource planning. Using a retrospective cohort design, we extracted clinical and management-related data from the records of 752 children with congenital anomalies and/or developmental delay who underwent CMA in an academic pediatric genetics clinic (2009–2011). Frequency distributions and relative rates (RR) of post-CMA medical recommendations in children with reportable and benign CMA results were calculated. Medical recommendations were provided for 79.6% of children with reportable results and 62.0% of children with benign results. Overall, recommendations included specialist consultation (40.8%), imaging (32.5%), laboratory investigations (17.2%), surveillance (4.6%), and family investigations (4.9%). Clinically significant variants and variants of uncertain clinical significance were associated with higher and slightly higher rates of management recommendations, respectively, compared with benign/no variants (RR=1.34; 95% CI (1.22–1.47); RR=1.23; 95% CI (1.09–1.38)). Recommendation rates for clinically significant versus uncertain results depended upon how uncertainty was classified (RR_broad=1.09; 95% CI (0.99–1.2); RR_narrow=1.12; 95% CI (1.02–1.24)). Recommendation rates also varied by the child''s age and provider type. In conclusion, medical recommendations follow CMA for the majority of children. Compared with benign CMA results, clinically significant CMA variants are a significant driver of pediatric medical recommendations. Variants of uncertain clinical significance drive recommendations, but to a lesser extent. As a broadening range of specialists will need to respond to CMA results, targeted capacity building is warranted.     

Parental experiences of ultrarapid genomic testing for their critically unwell infants and children

PurposeTo explore parental experiences of ultrarapid genomic testing for their critically unwell infants and children.MethodsParents of critically unwell children who participated in a national ultrarapid genomic diagnosis program were surveyed >12 weeks after genomic results return. Surveys consisted of custom questions and validated scales, including the Decision Regret Scale and Genomics Outcome Scale.ResultsWith 96 survey invitations sent, the response rate was 57% (n = 55). Most parents reported receiving enough information during pretest (n = 50, 94%) and post-test (n = 44, 83%) counseling. Perceptions varied regarding benefits of testing, however most parents reported no or mild decision regret (n = 45, 82%). The majority of parents (31/52, 60%) were extremely concerned about the condition recurring in future children, regardless of actual or perceived recurrence risk. Parents whose child received a diagnostic result reported higher empowerment.ConclusionThis study provides valuable insight into parental experiences of ultrarapid genomic testing in critically unwell children, including decision regret, empowerment, and post-test reproductive planning, to inform design and delivery of rapid diagnosis programs. The findings suggest considerations for pre- and post-test counseling that may influence parental experiences during the testing process and beyond, such as the importance of realistically conveying the likelihood for clinical and/or personal utility.