This study was conducted to explore the understanding and views of Indian public regarding the use of next generation sequencing technology. Use of NGS based testing in clinical as well as research settings is increasing. NGS based screening for carriers of recessive disorders and for multifactorial disorders is being offered to apparently healthy individuals. However, studies assessing public knowledge and attitude related to genomic tests is lacking in India. At this point, it is important to make policies for return of secondary findings as well as VUS for India. A cross-sectional study by Ganne et al. 2021 identified that there was a general lack of knowledge about the basic concepts in genetics among the general public in India[9]. Lack of India-specific database for disease-causing variants (40%-50% of which are novel) increases the burden of VUS. Hence, this questionnaire based study to get insights of Indian population will help in policy making and tailoring genetic counseling needs especially for genetic laboratories and genetic clinics in India.
This small study of 103 educated Indians, where 91.3% had completed at least a graduate level of education, showed that the majority had good understanding of the utility of NGS based testing after reading an information brochure (78% correct response in GP1).
Questions related to NGS not being able be detect complex multifactorial disorders like AIDS, Tuberculosis, etc. had mixed responses (32% correct response). This indicates that the utility of NGS for multifactorial disorders is difficult to understand and requires more clarity. We also observed that contrary to our assumption, public had a fair understanding of what a VUS result means (75.5% correct response). Recent studies on public knowledge of genetic testing have revealed mixed results [10, 11, 12, 13]. Better understanding of genetic testing among the respondents could be attributed to increased awareness and reporting of genetic testing in recent years. Over 90% of the respondents in this study had completed at least a bachelor’s level of education, the majority were of younger age group, and all had gone through the information sheet prior to filling out the questionnaires. We assume these factors could have significantly imputed to the correct responses in this study.
Almost a decade ago the National Human Genome Research Institute (NHGRI) had stressed on the need for education and awareness around genomics and its limitations for setting realistic expectations of these tests [14]. Our study corroborates this need for education and awareness as 69.9% respondents felt that every couple must undergo carrier screening before planning pregnancy and 64.1% recognized the need for all newborns to undergo NGS based screening. It is also equally concerning that 54.4% of the respondents would plan future pregnancy and undergo prenatal testing based on the VUS result in the proband. It suggests that the limitations and implications of VUS may not be clear to a sizeable population and more in-depth studies to understand these issues related to VUS among general population are needed.
The use of NGS based testing in newborns is very complex and various issues have been explored. A study on parental preferences on results from the Babyseq project identified that a majority (86.8%) of parents were interested in knowing their baby’s risk of developing a disease in childhood that is clinically actionable; 50.7% parents were interested in knowing results on unactionable childhood diseases; 84.6% were interested in knowing results of adult-onset secondary findings that are actionable; and 42.0% parents reported being interested in receiving a VUS result for their baby [15]. Few studies exploring the psychosocial effects of newborn genomic sequencing have identified no evidence of unfavorable psychosocial effect on families or children [16, 17]. Parents of children in acute care settings have reported disruptions in family bonding with the child after receiving results of ultrarapid genome sequencing [5], while others have reported low decisional regret, empowerment, and decisions regarding reproductive planning and options [18].
A positive attitude towards the uptake of NGS based test was observed in our cohort. Majority (85%) respondents agreed that they will get NGS based testing for screening carrier status, susceptibility for various diseases, assessing drug response, etc. and for all genes irrespective of whether their associated disorders are actionable or not. Previous studies assessing attitudes of public have also reported similar positive attitude towards the uptake of genetic tests [19, 20, 21, 22]. The respondents also felt that the results of NGS would impact them more positively by better preparing them mentally (87.4%) and for taking up necessary health measures based on the results (86.4%). There was generally mixed response to questions surrounding concerns related to NGS where 60.2% felt that they would be distressed knowing that the disease can be inherited by others in the family, 46.6% would feel guilty that they have passed on the genetic disease in the family, and about half (53.4%) of the respondents disagreed and 24.3% agreed to the statement ‘I feel it is better to not know the disease at all than having an uncertain result from NGS test.’
There was a favorable response related to sharing of results with others in the family. However, majority (77.7%) would not want the results shared directly with their relatives by the doctor/ GC without their permission. Studies exploring willingness to share genetic findings with relatives have also reported similar general willingness to share the results and forgo one’s own confidentiality [23, 24]. Moreover, there was a consensus among the respondents for knowing the secondary findings for treatable as well as untreatable conditions and VUS. These findings, in conjunction with the respondents’ willingness to make the genomic tests for population based applications such as for newborn and carrier screening, prenatal testing, etc., indicates that the respondents perceive these tests to be of high value. This would also suggest there is a possibility of unrealistic expectations from these tests given the promising areas of its utility and publicity. However, our study also suggests that many respondents (69.9% in SF for treatable, 67% in SF for untreatable and 72.8% in VUS conditions) would also like to ask their doctor/ genetic counselor to decide whether to report such unexpected findings. This indicates that the respondents appreciate the complexity of such results and would require their doctor/ GC’s assistance in result disclosure.
Our study has various limitations. Firstly, the small sample size does not represent the entire Indian population and does not reflect the educational status of the masses. The brochure and questionnaires designed were extensive therefore there is a possibility that educated participants might have responded. The understanding and responses may vary on the level of education. This study was based on the information provided by the brochure and the questions were hypothetical and were not real life experiences. However, studies on the patients or healthy individuals who will be undergoing the testing will be more insightful. Additionally, the positive attitude of population towards genomic testing indicates that the medical/clinical geneticists and GCs must be fully aware of the complex nature of the test results especially VUSs and SF and their implications. Also, the information provided to the public before offering NGS test need to clarify the uncertainties and complex issues of SF and VUS which the information brochure with limited information might not have been able to convey.
In conclusion, this pilot study demonstrates a relatively good level of understanding of the information sheet on next generation sequencing and its implications among the Indian population. Additionally, the public described willingness to have these tests available for general public for various clinical as well as personal utility. There was a general positive attitude related to sharing of the genomic test results with the relatives. Larger studies to get deeper insights in the general population may help in devising policies surrounding the use of genomic tests in clinical as well as public settings in India.