Public Knowledge about Monogenic Diseases and Attitudes Toward Expanded Carrier Screening in China

Background: Monogenic diseases affect about 10 in 1000 live births globally and account for 20% of infant mortality and 18% of pediatric hospitalizations. Many monogenic disorders could be prevented by offering expanded carrier screening (ECS) to the general population. The purpose of our study was to assess knowledge about monogenic diseases and attitudes toward ECS in China. Methods: Chinese individuals were invited to complete an online survey from July 11 to September 10, 2020. A total of 1663 questionnaires were collected. Statistical analysis was performed using IBM SPSS Statistics 26. Descriptive statistics were computed for all items. Categorical data were reported as frequencies and percentages with differences assessed by chi-square test. Results: The respondents’ total awareness rate ranged from 3.3% to 55.2%. Medical practitioners had more knowledge than non-medical practitioners. Knowledge about monogenic diseases was positively correlated with educational level. Most respondents showed a positive attitude toward ECS: 54.4% of respondents thought ECS was necessary, and 80.5% wanted to know more about monogenic diseases. Conclusions: Although the public had little knowledge about monogenic disease and ECS, most of them showed a positive attitude. Lack of knowledge is a barrier to application of ECS. Since pre-test counseling by a genetic counselor before ECS may not always be feasible, pre-test information may not be delivered by a trained genetic counselor. If clinicians are going to be the primary counselors, further education is necessary to improve their comfort and competence with this role.


Background
Although rare, monogenic disorders affect about 10 in 1000 live births globally (1) and account for 20% of infant mortality and 18% of pediatric hospitalizations (2).
Many monogenic disorders could be prevented by offering expanded carrier screening (ECS) to the general population (2). New advanced and decreasing costs of genetic analysis technologies such as next-generation sequencing (NGS) are enabling carrier screening research across a broader range of disorders (3)(4)(5).
In one of the earliest studies, Bell et al. (4) utilized NGS to screen for pathogenic mutations in 437 genes associated with severe genetic disorders. The authors reported that each patient's genome contained 2.8 recessive mutations on average (4). Another study showed that approximately one to two in every 100 couples are at risk of having a child with an autosomal or X-linked recessive genetic condition in the general population (6).
Increasing awareness of multiethnic backgrounds in the population, technological advances, and lower cost of multigene panel testing, have resulted in rapid development and clinical implementation of ECS (7).
The European Society of Human Genetics developed and published recommendations for the responsible implementation of ECS (3). In 2017, the American College of Obstetricians and Gynecologists (ACOG) reviewed ECS's role and suggested that ethnic-speci c, pan-ethnic ECS are acceptable strategies for prepregnancy and prenatal carrier screening (8). Despite these recommendations, ECS is not a common practice in most countries (9)(10)(11). Public perception of genetic carrier screening is diversi ed (12)(13)(14)(15)(16)(17).
In order to develop screening technology to meet the public's psychosocial and educational needs, healthcare providers need to understand public attitudes toward testing. The purpose of our study was to assess knowledge about monogenic diseases and attitudes toward ECS before commencing the practice.

Methods
Couples visiting the hospital for antenatal care were invited to complete an online survey by scanning a QR code from July 11 to September 10, 2020. A total of 1663 questionnaires were collected.
Prior to data collection, online informed consent was obtained from all participants. Their con dentiality was protected by each participant being assigned a unique identi cation (ID) number that was used on all data collection and statistical analyses. The Institutional Ethics Committee approved this survey.
Questionnaires were designed to assess the awareness of monogenic diseases and acceptance of ECS. They also compared the relevant knowledge of medical and non-medical practitioners.
Statistical analysis was performed using IBM SPSS Statistics 26. Descriptive statistics were computed for all items. Categorical data were reported as frequencies and percentages. The differences were assessed using the chi-square test, with P < 0.01 considered signi cant. undergraduate education, and 166 (10.0%) graduate education. In the respondents, 672 (40.4%) did not have children, and the remaining 991 (59.6%) had one or more living children. In the respondents, 149 (9.0%) had a family history of a genetic condition, and the remaining 1514 (91.0%) did not. In the individuals surveyed, 971 (58.4%) were currently pregnant (partner or self), 105 (6.3%) were considering a future pregnancy, and 587 (35.3%) did not plan to be pregnant. In the respondents, 292 (17.6%) were medical practitioners and 1371 (82.4%) were not.  Cross-analysis of medical and non-medical practitioners Table 2 shows the differences between medical and non-medical practitioners for seven items (Q1-Q7). The awareness rate of every item was higher for medical compared to non-medical practitioners. Six questions had signi cant differences (P < 0.01) but Q3 did not (P > 0.05).

Comparison of awareness rates for different educational backgrounds
The degree of awareness increased with the increase in educational level, especially in those with a college degree or beyond (Fig. 1). There were signi cant differences among respondents with different educational backgrounds (P < 0.01).

Attitudes toward ECS
Although overall the respondents had little knowledge about monogenic diseases and ECS, most had a positive attitude. Of respondents, 54.4% suggested that ECS was necessary, and 80.5% wanted more information about monogenic diseases (Table 3). Additionally, 51.7% of respondents thought that more pre-test counseling was needed, and 44.8% thought they would follow the provider's advice. Concerning the form of information access, 46.5% selected communicating directly with doctors, 17.9% preferred webinars, 17.3% favored brochures in outpatient waiting areas, 11.4% chose discussing with a nurse, and 6.8% opted for self-web search.

Comparison of attitudes toward ECS for different educational backgrounds
For people with technical secondary education or beyond, the percentage who thought ECS was necessary increased with educational level (Fig. 2). In contrast, the proportion of people who would choose to follow the provider's advice decreased with the rise of educational level. For people with technical secondary education or beyond, as the education level increased, more people chose to consult before ECS, and fewer people chose to follow the provider's advice (Fig. 3).
The number of diseases, strategy, period, and cost of screening when considering ECS The questionnaire also asked respondents about the number of diseases to be screened: 58.1% suggested the more, the better; 34.1% preferred the most common ones; and 5.6% thought the less, the better. The remaining 2.2% made no comments. When asked about screening strategy, 83.0% preferred simultaneous screening of couples, while 17% preferred step-by-step screening (one partner is screened rst, and then the other if the partner is a carrier). Most respondents chose premarital (43.1%) and preconception (33.1%) counseling. For an acceptable price, 71% chose less than 1,000 yuan (100 Euro). All of the above are listed in Table 4. Reasons for rejecting ECS Among the respondents, 35.2% rejected ECS because the more they knew, the more they were likely to worry, 33.3% rejected ECS for economic reasons, 6.5% for lack of interest, and 25% for other reasons (Table 4).

Main ndings
Lack of knowledge is a barrier to the use of ECS. This study showed that only a small number of people in the study population knew about monogenic diseases and ECS ( Table 2). Most of them wanted to get information through direct communication with doctors (Table 3). However, if a patient has little knowledge about ECS, their doctor needs to provide them with information. Benn et al. reported that only one-third of providers were comfortable with pre-test counseling, and less than 25% were satis ed with reviewing results. The main concerns included the time needed for counseling and coordinating follow-up studies and comfort with counseling after a positive result (18). A recent study reported that the lack of comfort with ECS counseling and varying beliefs surrounding ECS continue to hinder its utilization (19).
Our cross-analysis showed that medical practitioners had a signi cantly higher degree of awareness compared to non-medical practitioners. However, medical practitioners had de cient awareness of the combined incidence of monogenic disease, with only 5.1% of them correctly answering the relevant question (Q3, Table 2), compared with 2.9% of non-medical practitioners (P > 0.05). Since speci ed pretest counseling by a genetic counselor before each ECS may not always be feasible, pre-test information may be delivered through a provider without genetics training. In many cases, providers do not offer patients carrier screening due to a lack of con dence and knowledge concerning genetics (20). As genetic technologies evolve and are more incorporated into clinical practice, clinicians' knowledge is essential.
Although the overall respondents had little knowledge about monogenic disease and ECS, most showed a positive attitude (Table 3). This is consistent with the ndings of several studies (13,(15)(16)(17)21).
The main limitation of pre-test counseling for ECS is that it is impractical to thoroughly discuss all the diseases and conditions included in the panel. This is in contrast to pre-test counseling for classical carrier screening programs, which includes information regarding the natural history, detection rates, and prior and posterior carrier probabilities of a limited number of diseases. Thus, the use of ECS necessitates modi cation of this model (22).
There was one very interesting nding. Although highly educated people had more knowledge of ECS than less-educated people, when asked if they would like to know more background or get more consultation, they seemed more eager to learn. In our data, highly educated people were more likely to choose "necessary" (they wanted more information before making a decision); however, less-educated people were more likely to choose "follow the provider's advice" (indicating passive acceptance).
The provider's personal opinion is critical to the people who tended to follow the provider's advice. Especially for complex consultations such as ECS, it is time-consuming to achieve fully informed consent. Even highly educated people may not be able to fully understand ECS through consultation. The nal choice may be related to the provider's preference.
Some ndings in our study were consistent with the recommendations of ACOG, suggesting that carrier screening and counseling should ideally be performed before pregnancy (23); in our study, most respondents chose premarital (43.1%) and preconception (33.1%). ACOG also suggested concurrent screening for the patient and her partner if there are time limitations for decisions about prenatal diagnostic evaluation (23). In our survey, 83.0% preferred the simultaneous screening of couples.

Strengths and limitations
The strengths of our study include that all surveys were anonymous, increasing the likelihood of truthful responses. Furthermore, the survey was distributed nationally, giving a wide geographic distribution of thoughts and beliefs. One limitation is that all the questions were pre-set in the answers' scope, thus limiting the respondents' answers and may omit some detailed and in-depth information. For example, among the reasons for rejecting ECS, due to the limited options we provided, 25% of the respondents chose "other reasons". Given that the survey was electronically distributed, the responses could not be clari ed.

Conclusion
Our study showed that, although the public had little knowledge about monogenic diseases and ECS, most showed a positive attitude toward it. Lack of knowledge is a barrier to the application of ECS. Since pre-test counseling by a genetic counselor before ECS may not always be feasible, an experienced genetic counselor may not deliver the pre-test information. If clinicians are going to be the primary counselors, further education is required to improve their comfort and competence with this role.