Impact of genomic literacy components on genetic testing decision-making in the general Japanese population in the 20s and 30s

In promoting genomic medicine, genomic literacy, which is the public’s ability to acquire and utilize the knowledge and skills related to genetics and genomes, requires urgent improvement. This study determined how the three components of genomic literacy (genetic/genomic knowledge, health numeracy, and interactive and critical health literacy) are associated with risk and benefit perception for genetic testing and decision-making related to genetic testing. Using an online questionnaire, we surveyed genetic/genomic knowledge, health numeracy, interactive and critical health literacy, risk and benefit perception of genetic testing, and intention toward genetic testing of 857 Japanese citizens (aged 20–39). A vignette was created to measure the intention toward genetic testing, and respondents were asked about their willingness to undergo genetic testing and to share the results with their partners and children. The path analysis, which was done by creating a path diagram revealing the relationship of the three components with risk and benefit perception, revealed that genetic and genomic knowledge and interactive and critical health literacy affected the respondents’ intention to undergo genetic testing via recognition of the benefits of such testing. Further, it was suggested that health numeracy affects benefit perception through risk perception toward genetic testing. However, the goodness of fit of this model for the intention of conveying positive results to partners and children was relatively low, thus indicating that the hypothetical model needs to be reexamined.


Unfunded studies
Enter: The author(s) received no specific funding for this work. The purpose of the study and the handling of personal information were explained on the webpage, and responses were considered to be the acquisition of consent.  with the rapid market expansion of Direct-to-Consumer Genetic Testing business and the 3 associated media coverage, the general public has more opportunities to hear words such as 50 "genomes" and "genes." Currently, a person can attain their own genome information, which 51 requires the ability to have and utilize knowledge about genetics and genomes. 52 However, it is difficult for the general public to fully understand genomic medicine due to its 53 complexity and the high level of expertise required in the technology; as such, the general public's 54 knowledge of heredity and genomics is insufficient [2,3]. Furthermore, the genetic and genomic 55 information provided through the media is not always correct, and many people find it difficult 56 to distinguish between valid and invalid genetic and genomic information [2,4]. Therefore, there 57 are excessive expectations and misunderstandings, and also concerns that the acquisition of biased 58 genetic and genomic information and incorrect knowledge may lead to inappropriate behavior. 59 It has been noted that knowledge about genetics and genomics alone does not lead to 60 appropriate action. Based on the concept of health literacy, the American Public Health 61 Association [5] states that the general public needs to acquire the knowledge and skills necessary 62 According to a study of the processes by which risk and benefit perceptions influence decision-83 making, the following association has been found in the risk perception process: general tendency 84 → situation recognition factor → option recognition factor → behavior. This suggests that the 85 decision-making process in which each individual's abstract way of thinking and recognizing 86 influences the recognition of a concrete object, and as a result determines their behavior, exists 87 securely [13]. Furthermore, it has been confirmed that knowledge and critical thinking define 88 intention through risk and benefit perception as determinants of acceptance of risk [14]. It has 89 also been pointed out that numeracy, which is an important element of health behavior, affects 90 risk and benefit perception [15]. Therefore, in this study, we assumed a process in which the three 91 components of genomic literacy affect decision-making through risk and benefit perception and 92 examined their effects on decision-making. 93 Although genomic medicine is becoming widespread in Japan, there are still few opportunities 94 in which the general public are required to make decisions because related genetic tests and 95 treatments are not yet commonly known. Therefore, this study presented a virtual scene in the 96 form of a vignette to evaluate decision-making in situations related to taking genetic tests. Prior 97 studies have indicated that young people have inadequate knowledge of general genetics and 98 genomics and do not accurately estimate risk [16]. Therefore, we surveyed members of the general public in their 20s and 30s, who were likely to be exposed to genomic medicine in the 100 near future. 101 Based on the above understanding, this study considers genetic/genomic knowledge, health 102 numeracy, and interactive and critical health literacy as components of genomic literacy. It 103 examines the impact of risk and benefit perception on decision-making relating to genetic testing. 104 The purpose of the study and the handling of personal information were explained on the 115 webpage, and responses were considered to be the acquisition of consent. 116

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The respondents were asked about their sex, age, marital status, children, occupation, level of 119 education, whether or not they had taken biology during high school, whether or not they had 120 learned about genetics, and whether or not they or someone in their family had a genetic disorder. 121

Genetic/genomic knowledge
It has been pointed out that the existing genetic and genomic knowledge scales are biased towards 123 assessing professional and academic knowledge [17]. Therefore, in this study based on the 124 surveys and scales of previous studies [18-21], 11 items of genetic and genomic knowledge 125 necessary for decision-making on genetic testing were created based on the advice of seven 126 genomic medicine doctors and researchers. These eleven items were "characteristics of genetic 127 information" (three questions), "relationship between gene mutation and disease" (three 128 questions), and "knowledge of genetic testing" (five questions). In each question, the respondent 129 was asked to select one answer from three options: "yes," "no," and "unsure." "Yes" was assigned 130 one point, "no" or "unsure" was assigned 0 points, and the total score of genetic/genomic 131 knowledge was considered as the "genetic/genomic knowledge score" (score range: 0 to 11 132 points). 133

Health numeracy
134 Health numeracy was measured using the validated scales "the health numeracy test" by Miyoshi 135 et al [22]. The questions in the health numeracy test are categorized as follows: "% and magnitude 136 of risk" (four questions), "conversion from frequency to %" (one question), "calculation of 137 probability" (one question), "conversion from probability to frequency" (two questions), and 138 "reading tables and graphs" (two questions). "Yes" was assigned 1 point, "no" or "unsure" was 139 assigned 0 points, and the total score of the 10 items in the health numeracy test was considered 140 as the "health numeracy score" (score range: 0 to 10 points). 141 literacy (a higher level of health literacy than functional health literacy). In this study, the 145 measurement was carried out using the CCHL scale, which consists of five items. Responses are 146 based on a five-point scale with "strongly agree" (5 points) as the highest and "strongly disagree" 147 Genomic literacy and genetic testing decision-making 7 (1 point) as the lowest. The total score of the CCHL scale is considered as the "CCHL score" 148 (score range: 5 to 25 points). 149 The content of questions on risk perception for genetic testing consists of five items such as "if 153 I discover a genetic mutation (genetic change) associated with a disease, I will continue to be 154 anxious about developing it in the future," and "if I discover a genetic mutation (genetic change) 155 associated with a disease, it will put a strain on my family and future children." 156

Risk perception and benefit perception for genetic testing
The content of the questions on benefit perception for genetic testing consists of five items such 157 as "if I discover a disease-related gene mutation (genetic change), it will help me prevent, detect 158 early, and choose treatment for my own disease," and "if I discover a genetic mutation (genetic 159 change) related to a disease, it will help prevent, diagnose early, and treat the disease in my family 160 and future children." The response to each question is based on a five-point scale with "strongly 161 agree" (5 points) as the highest and "strongly disagree" (1 point) as the lowest value. 162 Genetic testing decision-making 163 Although genomic medicine is becoming widespread in Japan, there are still few situations in 164 which the general public makes decisions because genetic tests and it treatments have not become 165 common. Therefore, in measuring behavioral intention toward genetic testing, we used a method 166 of assessing behavioral intention by presenting a situation regarding genetic testing in the form 167 of a vignette; a vignette assumes family medical history and genetic risk. 168 The vignettes were created based on the advice of seven genomic medicine doctors and 169 researchers. In this study, behavioral intention was regarded as decision-making in a narrow sense, 170 and the term "behavioral intention" was used for measuring decision-making. 171 Genomic literacy and genetic testing decision-making 8 Vignette for respondents 172 "You are in your twenties and engaged. Your mother got sick at the age of 40. Your grandmother 173 had also developed the same illness. You are in good health now. It is said that with 5-10% of 174 cases, this disease is hereditary. If a genetic test is performed and a positive diagnosis is made, 175 the probability of developing the disease in your lifetime is said to be 25-85%." 176 Regarding the question items on behavioral intentions, the question on "the respondent's 177 genetic testing intention" is as follows: "Do you plan on taking a genetic test for this disease?" 178 The response to this question is based on a five-point scale with "I will take the test" (5 points) as 179 the highest and "I will not take the test" (1 point) as the lowest. The question on "intention to 180 convey positive results to my partner" is as follows: "The genetic test revealed that you were 181 positive for a specific genetic mutation. Would you share this result with your partner?" The 182 question on "intention to convey positive results to your children" is as follows: "The genetic test 183 revealed that you were positive for a specific genetic mutation. Would you tell this result to your 184 future children?" The responses to both questions are based on a five-point scale with "I will tell 185 them" (5 points) as the highest and "I will not tell them" (1 point) as the lowest. 186

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In the comparison of the average scores of the three components of genomic literacy, risk 188 perception, benefit perception, and behavioral intention toward genetic testing by attribute, the 189 effect size d was obtained by conducting a t-test on sex, age group, marital status, children, 190 occupation, whether the respondent took biology in high school, whether the respondent had an 191 educational background in genetics, and whether the respondent or a family member had a genetic 192 disease. For and level of education, one-way ANOVA was performed to obtain the effect size η 2 . 193 Next, we performed a correlation analysis to examine the relationships between the variables.

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The percentages of correct answers for genetic and genomic knowledge are shown in Table 2. 213 Table 1 shows a comparison of the average scores of the three components of genomic literacy 214 by attribute. The average genetic/genomic knowledge score was 5.67 points (standard deviation: 215 those with a high level of education, medical professionals, those who took biology in high school, 217 those who had studied genetics, and those who had a genetic disorder or a family member with a 218 genetic disorder had significantly higher genetic/genomic knowledge scores. The average score 219 for health numeracy was 7.11 points (standard deviation: 2.78, range: 0 to 10 points). As a result 220 of comparing the health numeracy scores by attribute, the health numeracy scores were 221 significantly higher in men and those with a high level of education. The average CCHL score 222 was 17.84 points (standard deviation: 3.68, range: 5 to 25 points). As a result of comparing CCHL 223 scores by attribute, those with a high level of education, medical professionals and those who had 224 studied genetics had significantly higher CCHL scores. 225 Table 2. The correct answer rates for genetic/genomic knowledge 226 1 One's genetic information can change over one's lifetime. 2 Genetic testing may predict future disease onset. 3 I share some of my genetic information with my blood relatives. 4 If you have a genetic mutation (change in a gene) that is associated with a disease, you will always get the disease. 5 If you have no blood relatives with a genetic disease, you do not have a genetic mutation (genetic change). 6 Genetic mutations (changes in genes) that occur in somatic cells (cells other than sperm and oocytes) are passed on to the next generation. 7 As genetic and genomic research advances, the probabilities and interpretations of the relationship between disease and heredity may change. 8 Even if a genetic mutation (change in a gene) is found that may cause disease, there may be no effective treatment currently available. 9 Knowing that a person has a genetic mutation (change in a gene) that predisposes him or her to develop a disease may lead to prevention or ear 10 If you have a genetic mutation associated with the disease (change in a gene), it is possible that your blood relatives may have a similar mutatio 11 Probability of having a child with a genetic disease is 50% means that for every four children you have, two will have the disease. 227 228 Risk perception and benefit perception for genetic testing 229 We confirmed the ceiling effect (mean score + standard deviation ≧5) and floor effect (mean 230 score -standard deviation ≦1) for five items on risk perception and five items on benefit 231 perception for genetic testing. As a result, no ceiling effect or floor effect was observed for any 232 of the five items on risk perception or the five items on benefit perception.
Next, we performed a principal component analysis on five items for risk perception and five 234 items on benefit perception for genetic testing. As a result, in the five risk perception items, the 235 load of the first component was .734 to .789, and the contribution rate was 59.8%. In the five 236 benefit perception items, the loading amount of the first component was 0.80 to 0.82, and the 237 contribution rate was 65.1%. The total score was calculated for each of the five items on risk 238 perception and the five items on benefit perception. Hereinafter, the total scores are referred to as 239 the "risk perception score" and "benefit perception score." The score range is 5 to 25 points in 240 each case. 241

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To investigate the relationships between the variables of the three components of genomic literacy, 244 risk perception scores, benefit perception scores, and behavioral intention toward genetic testing, 245 a correlation analysis was performed (Table 3). The partial correlation coefficient was calculated 246 with the presence or absence of hereditary disease of the person or family as a control variable. 247 Consequently, a significant positive correlation was found between the genetic/genomic 248 knowledge score, the health numeracy score, the CCHL score and the benefit perception score. 249 The direct impact of components of genomic literacy on behavioral 253 Genomic literacy and genetic testing decision-making 13 intention toward genetic testing 254 To investigate the effects of genomic literacy components on behavioral intention toward genetic 255 testing, those who had a genetic disorder or a family member with a genetic disorder were 256 excluded and a multiple regression analysis was performed, with behavioral intention towards 257 genetic testing as the dependent variable and the three components of genomic literacy as the 258 independent variables (Table 4). Consequently, the adjusted coefficient of determination was .073 259 to .160, which was a significant value at the 1% level for all behavioral intentions toward genetic 260 testing. It was shown that health numeracy and CCHL among the independent variables 261 influenced all the items on behavioral intention toward genetic testing. 262 Explanation and results of the hypothetical model 266 We set up a hypothetical model where components of genomic literacy (genetic/genomic 267 knowledge, health numeracy, and CCHL) influenced behavioral intentions toward genetic testing through risk and benefit perception, created a path diagram, and performed path analysis after 269 excluding those who had genetic disease or had a family member with a genetic disease. 270 The effect on "one's intention toward genetic testing" is as shown in Figure 1, but a significant 271 path was found where genetic/genomic knowledge and CCHL affect one's intention toward 272 genetic testing through benefit perception. However, risk perception did not directly affect one's 273 intention toward genetic testing. Since the path coefficient between risk perception and benefit 274 perception is high, it was interpreted that risk perception affects benefit perception and contributes 275 to the formation of one's intention toward genetic testing. In other words, we confirmed that health 276 numeracy affects one's intention toward genetic testing from risk perception to benefit perception. is considered to be one of the prerequisites for health behavior, enhancing the genetic/genomic 295 knowledge of the general public will lead to appropriate decision-making in the genetic/genomic 296 domain as well. 297 Not only genetic/genomic knowledge but also health numeracy and interactive and critical 298 health literacy had an influence on behavioral intention toward genetic testing. Enhancing 299 genetic/genomic knowledge leads to appropriate decision-making, and the genomic literacy 300 scales [20,28,29] and evaluation methods [30] used so far have mainly only measured 301 genetic/genomic knowledge and examined its relationship with decision-making. The results of 302 the present study show that the three components of genomic literacy influence one's intention 303 toward genetic testing. Therefore, it will be necessary to proceed with research on genomic 304 literacy, including not only genetic/genomic knowledge, but also health numeracy and interactive 305 and critical health literacy. 306 In addition, the genetic and genomic knowledge required for decision-making may change with 307 rapidly advancing genomic medicine. However, health numeracy and interactive and critical 308 health literacy are universal abilities that are not situation-dependent. From the results of this 309 study, it can be said that health numeracy and interactive and critical health literacy are important 310 decision-making components of genomic literacy. 311 To clarify the process by which genomic literacy influences decision-making, a model was 312 assumed in the present study in which the behavioral intention toward genetic testing was 313 influenced through risk and benefit perception based on previous studies. In other words, we 314 created a path model of intention toward genetic testing from the components of genomic literacy 315 through the cognitive factors of risk and benefit perception and conducted path analysis to 316 examine it. Thus, the association of the genomic literacy component → risk and benefit perception 317 → intention toward genetic testing was found, and the model showed high goodness of fit. This association supported the results of previous studies regarding the decision-making process 319 [13,14,31]. Therefore, it was suggested that there is a decision-making process in which the three 320 components of each individual's genomic literacy influence their intention toward genetic testing 321 through risk and benefit perception on genetic testing. 322 In this study we have shown the path from risk perception to benefit perception to the influence 323 on one's intention toward genetic testing. In previous studies [32-34], there was often a negative 324 correlation between risk and benefit perception, but in the present study, there was a positive 325 correlation between them. However, Lloyd et al. reported a positive correlation between patient 326 risk and benefit perception for carotid endarterectomy [35]. The reason is that patients recognize 327 that high-risk surgery also has high benefits. In the present study as well, it is possible to recognize 328 high risks and high benefits for new tests. In addition, a survey of food risk perception reported 329 that the high numeracy group showed a positive correlation between risk and benefit perception 330 after information provision compared to the low numeracy group [36]. It is suggested that those 331 with high numeracy may consider the risks and benefits in a well-balanced manner by receiving 332 numerical information. Therefore, the positive relationship between risk and benefit perception 333 in the present study is considered to be a valid result. 334 In previous studies on numeracy, those with high numeracy made appropriate decisions based 335 on the numbers themselves. However, people with low numeracy are susceptible to non-numerical 336 information (emotions and moods) and cognitive bias [37,38]. In addition, Klaczynski et al. 337 showed that numeracy facilitates rational risk decision-making in people with high critical 338 thinking attitudes [39]. The path analysis model in the present study revealed that health numeracy 339 did not directly affect behavioral intention toward genetic testing but did affect behavioral 340 intention through a process via risk perception. Increasing numeracy can lead to a better 341 understanding of information on probability and statistics and generally better decision-making. 342 The same is considered to be the case for behavioral intention toward genetic testing. as to specific health problems, but also to provide information to their neighbors. As revealed in 348 this study, CCHL influences both risk and benefit perception and has been shown to be an 349 important component of genomic literacy. Regarding health problems related to genes and 350 genomes, new knowledge is required due to the characteristics of genomic research, and it is 351 necessary to update one's own knowledge. Therefore, interactive and critical health literacy can 352 be said to be an important factor in behavioral intention toward genetic testing. 353 In this light, it was shown that a model in which the three components of genomic literacy 354 influence behavioral intention through risk perception and benefit perception is effective for one's 355 own intention toward genetic testing. 356 We believe that our study makes a significant contribution to the literature because we clarified 357 the three components of genomic literacy (genetic/genomic knowledge, health numeracy, 358 interactive and critical health literacy) which, through the recognition of the benefits and risks of 359 genetic testing affect the respondents' intention to undergo such testing. 360 Limitations of this study 361 We created a path model of "intention to convey positive results to partners" and "intention to 362 convey positive results to children" from the components of genomic literacy through cognitive 363 factors of risk and benefit perception and performed path analysis. However, the goodness of fit 364 of the model was lower than that for "one's intention toward genetic testing," indicating that the 365 hypothetical model needs to be reexamined. The reason for this is considered to be the peculiarity 366 of the genetic information handled in genetic testing. The peculiarities of genetic information 367 include the fact that it is information unique to a person and does not change or cannot be changed in their lifetime (invariance), and further that there is commonality regarding such information 369 with other individuals in a genetically-linked family [24,45]. There is also the predictability of 370 genetic information in that it can predict a future that was previously unknown. In other words, 371 although an individual's genetic information is unique to that individual, it has the duality of 372 already being shared by their family. Sakurai   Click here to access/download; Figure;renamed_b121d.pptx