Precision assessment of public attitudes toward genetic testing

While I was visiting Shanghai Children's Hospital in April 2016, I could not help but notice “ (Precision Poverty Alleviation)” in the front-page headline of a local newspaper in the cafeteria. “Precision” has surely become a trendy word recently. Chinese President Xi first proposed the “precision poverty alleviation” strategy during his visit of autonomous regions of certain minorities in rural China in November 2013 and urged its implementation in December 2015. The strategy aims to enhance the relevance and efficacy of poverty relief effort through targeted assistance for the poor and enabling self-help based on their specific circumstances for sustainable poverty reduction. Coincidentally, President Obama of the United States announced the Precision Medicine Initiative in his State of the Union Address on January 20, 2015. The initiative aims to deliver the right care to the right patient at the right time, while taking into account individual genetic, environmental, and lifestyle differences. The basic idea behind “precision” is the same: to solve specific problems in different situations via a targeted approach to maximize efficacy.

Among all the factors that influence an individual's health, constitutive genetic variations are the most predictive, because they largely remain unchanged throughout one's lifespan. Established pathogenic variants in an individual's genome are known to cause genetic disorders or be passed on to the offspring. Precise diagnosis to identify the exact genetic etiology of hereditary disorders is a prerequisite for targeted therapy. For example, new medications have become available for patients with cystic fibrosis with certain pathogenic genetic variants in the CFTR gene[Wainwright et al., 2015], and new gene therapies approaches are also being developed to treat genetic disorders [Stein et al., 2012; Bainbridge et al., 2015]. However, very few targeted therapies are available at the present, the development is very costly, only a small number of patients with specific genetic lesions may benefit, and there are often considerable side effects and expenses associated with those specific treatment options. An alternative and superior approach, a doctrine purported in “(The Emperor's Inner Cannon),” the ancient Chinese medical text more than two millennia ago, would be to prevent diseases from happening in the first place.

For genetic disorders, prenatal and preimplantation genetic testing (PGD) may offer an opportunity to achieve preventive precision medicine. With the advance of new technologies, it is now possible to perform comprehensive genetic tests to inform people not only of the risk of having genetic disorders for themselves but also of their chance of transmitting the gene to future generations. A healthy couple may have a child affected with some recessive disorders if both parents are heterozygous carriers of pathogenic variants in the same gene and the child inherits both affected copies of the gene. Prenatal testing can reveal the fetus’ genotype, and PGD coupled with in vitro fertilization techniques can even allow selection of embryos with the desired genotype. While technologically feasible, there are considerable ethical and social issues surrounding these procedures. Who makes the decision to be tested? Who should be tested? What genes or for what diseases should be tested? Should insurance cover the procedures? What to do with the test results? We do not have good answers to these questions. Besides, answers could be very different depending on who answers them.

In the study by Fu et al. [2016], the authors surveyed 1,500 people mainly from two colleges in Shanghai, China, half by printed questionnaires and half online, and received >60% completed surveys for both. This was one of the largest studies of this kind. It precisely assessed the attitudes of the educated young population in urban China toward genetic testing of recessive hereditary deafness for the purpose of carrier screening and prenatal diagnosis. They found that the respondents generally hold a positive view toward genetic testing, even more so for individuals without a family history of hearing loss, which is consistent with previous studies of smaller scales on families with deaf members [Brunger et al., 2000; Fu et al., 2010; Nahar et al., 2013].

It should be noted that subjects in this new study representing the general public and parents of deaf children participated in previous studies largely have normal hearing. Studies have indicated that affected individuals have more-positive attitudes toward the condition they have than do others and hold more-negative attitudes toward genetic testing. Deaf and hard of hearing adults of reproductive age were reportedly less interested in genetic testing than hearing counterparts [Martinez et al., 2003]. Another study of Deaf adults in the United Kingdom 18 years ago also showed a more negative attitudes toward genetic testing [Middleton et al., 1998]. However, tremendous advances have been made in the field of human genetics, resulting in positive public opinions over time [Henneman et al., 2013]. Hence, some of the differences observed across these studies may be partially explained by improved understanding and acceptance of genetic testing in general regardless of disease status. Nevertheless, it would still be interesting to assess Deaf people's current opinion on genetic testing.

Similarly for prenatal testing, 89% of respondents representing the educated young urban Chinese population were in favor of prenatal diagnosis for recessive hereditary hearing loss and 81% of those would consider to terminate an affected pregnancy [Fu et al., 2016], which echoes the findings in an earlier study of an Indian population where 93% expressed interest in prenatal diagnosis and 73% would consider termination of an affected fetus [Nahar et al., 2013]. Interestingly, a comparable percentage (87%) of respondents in the study by Brunger et al. [2000] in the United States were interested in prenatal testing, but none would consider termination.

These results are not surprising. In a recent study, Winkelman et al. [2015] investigated public perspectives on the use of PGD in the United States, and found that the majority of the surveyed population supported PGD for diseases fatal early in life and for lifelong disability, but only a minority supported for diseases that manifest late in life and much fewer for sex selection, physical traits, and personality traits. Hearing loss is a heterogeneous condition. Some rare forms of hearing loss may be fatal early in life, but most individuals with hearing loss have a life expectancy similar to hearing people. If treated early, most people with hearing loss can lead a normal life. With the help of hearing aids and cochlear implants, a lot of deaf people can hear and talk. Even without hearing, many deaf people communicate using sign language. In fact, members of the Deaf community who live in Deaf culture view deafness as a difference in human experience rather than a disability [Israel et al., 1992]. However, regardless of treatment, deafness is a lifelong condition, and the cost for rehabilitation is not trivial. Therefore, a positive view towards carrier screening and prenatal testing for hearing loss is expected.

However, why do attitudes toward termination of an affected pregnancy differ so much between the educated young urban Chinese population and parents of deaf children in the United States, despite similar level of interest in prenatal testing? This is because people are interested in testing for different purposes. The main reason for the predominantly hearing Chinese population to seek prenatal testing is to have a hearing baby. This is assumed, because a respondent was only asked to explain if not interested [Fu et al., 2016], but it has been shown that the top priority is a healthy baby for Chinese couples [Li et al., 2016]. In contrast, being able to prepare for having a deaf child was the primary reason for testing given by most parents of deaf children in the United States [Brunger et al., 2000]. It would not be difficult to understand if we take the economic, cultural, and sociopolitical environment into consideration.

Economic burdens obviously contribute to the difference. Annual per capita gross national income in the United States was seven times that in China (http://data.worldbank.org/indicator/NY.GNP.PCAP.CD). Medicare and most insurance companies provide benefits to cover the cost of cochlear implants, hearing aids, early intervention programs, and other rehabilitation options in the United States, which is not the case in China. The cost of the cochlear implant itself would equal to an average family's 10 years’ total income. Similarly most people in India cannot afford cochlear implants either [Krishnamoorthy et al., 2014]. Costs of rehabilitation remain prohibitive in developing countries, leaving primary prevention (i.e., identifying the etiology of hearing loss) the preferred option [Olusanya et al., 2014].

Another major factor that influences people's decision-making on genetic testing is likely the cultural perception of disability. Attitudes towards disability and disabled individuals vary widely between cultures. A negative correlation between uptake of prenatal testing and attitudes toward disability has been hypothesized [Bell and Stoneman, 2000]. In Western cultures, individuals with disabilities are merely regarded as being different or an inconvenience, and accessibility facilities are mandated to help compensate the disadvantage. On the contrary, in Eastern culture, disabilities are often treated as punishment and stigma, not only to affected individuals but also to their family members. Accessibility design and facilities such as wheelchair ramps, Braille, signage, elevators, audio signals at crosswalks, and so on, are commonplace in the United States, but quite rare in China. The first handicap parking stickers were introduced in the United States in 1973, yet they did not appear in China until 2010. Without rehabilitation due to economic constrains, hearing impaired individuals in China cannot reach their full potential and have limited opportunities to employment and social advances. There are also insufficient medical, educational, and social welfare facilities to meet their needs in China. All these lead to a lower quality of life for deaf families than the general public.

Economic conditions and cultural beliefs directly shape the sociopolitical environment. Eugenics has been negatively associated with Nazi and the Holocaust, and been gradually abandoned in Western countries since the end of World War II, as it is considered a violation of human rights. The pro-life and pro-choice debate on abortion has been a major topic in every presidential debate since the US Supreme Court's Roe v. Wade ruling for four decades. In contrast, eugenics is written into the Chinese legislation [Wertz, 1998], and the “one-child” population control policy launched in 1979 was only replaced by the “two-child” policy effective this year. Forced sterilization and induced abortion was once mandatory there [Wertz, 1998; Li, 2012]. As a result, abortion is less a social stigma than disabilities in China, and than in Western Cultures. Also written in the Chinese law is offspring's obligation to support and comfort their elderly parents financially. A disabled child is, therefore, less desirable.

Of course, attitudes do not equal to behavior. Survey responses do not always indicate what people will actually do. Those who completed the surveys may be more interested in the subject matter, thus biased toward a more positive attitude. For example, a majority of parents during early postpartum period are interested in newborn genomic testing [Waisbren et al., 2015], yet only a small proportion actually participated in research studies of newborn genomic testing. Another intrinsic limitation of a “precision” approach is the lack of generality thus findings inevitably limited to the sample population. The authors duly acknowledged these caveats in the study [Fu et al., 2016]. More studies of other disorders or in other populations with different cultural and social background will provide much-needed basis for counseling patients and families in considering genetic testing in the era of precision medicine.

The poverty line was about $5,000 per person in the United States in 2015 (https://aspe.hhs.gov/2015-poverty-guidelines), which is similar to the Chinese per capita annual disposable income (http://www.tradingeconomics.com/china/disposable-personal-income). Meanwhile, the Chinese poverty line was only 2,300 Chinese Yuan (<US$350) per person in 2015. However, even with such low standard, there are still more than 70 million people in poverty in China. No wonder President Xi would prioritize “precision poverty alleviation,” while President Obama has the luxury to promote “precision medicine.” Regardless, attitudes toward genetic testing for hereditary disorders including deafness have become more positive over the years, although why the information are sought and how it may be used to make medical and personal decisions could be strikingly different due to economic, cultural, and sociopolitical conditions. Therefore, a “precision” approach is needed to probing specific population's view on genetic testing, so that targeted genetic counseling may be delivered to patients and families.