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Brittany Strobel, Lauren McManus, Shirley Leong, Frederic Blow, Valerie Slaymaker, Wade Berrettini, Adam J. Gordon, Charles O'Brien, David Oslin, A Cross-Sectional Study of Attitudes About the Use of Genetic Testing for Clinical Care Among Patients with an Alcohol Use Disorder, Alcohol and Alcoholism, Volume 48, Issue 6, November/December 2013, Pages 700–703, https://doi.org/10.1093/alcalc/agt130
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Abstract
Aim: Modification and individualization of medical treatments due to genetic testing has the potential to revolutionize healthcare delivery. As evidence mounts that genetic testing may improve treatment decisions for patients with alcohol use disorder (AUD), we explored patient concerns and attitudes toward genetic testing. Methods: Subjects of two USA cross-sectional AUD studies were surveyed regarding their attitudes regarding the use of genetic testing for AUD treatment. Results: Four hundred and fifty-seven participants were surveyed. Overall, subjects showed a high degree of willingness to provide DNA for clinical use and recognized genetics as important to the pathophysiology of a number of disorders including AUD. There were, however, significant concerns expressed related to insurance denial or employment problems. Conclusion: We found that patients enrolled in AUD studies had some concerns about use of genetic testing. The patients in these two samples were, however, willing and knowledgeable about providing DNA samples.
INTRODUCTION
There is a large scientific literature demonstrating a link between genetics and the risk and addiction pathophysiology, including alcohol abuse and alcohol dependence (or alcohol use disorders (AUDs)) (Kendler et al., 1992, 1997; Prescott and Kendler, 1999). It is possible that understanding these genetic factors will influence treatments and possible cures. However, with these advances have also come ethical concerns over genetic testing, including when it is warranted and what is done with the results and DNA samples.
Studies almost exclusively outside of the addiction field have given us some insight into people's perceptions about genetic testing and how those perceptions impact decisions regarding different aspects of healthcare and family. It is known that people showed high interest in undergoing genetic testing for many medical and psychiatric disorders (Lawrence and Appelbaum, 2011). Willingness for genetic testing appears to be affected to some degree by the usefulness of the resulting information for prevention or treatment, as well as the conclusiveness of the results. While reported interest in genetic testing was rated highly, the rate of utilization is generally lower. For example, while the authors found that 40–79% of people at risk of Huntington's disease expressed some interest in genetic testing, only 9–20% actually utilized the test. Patients have also raised concerns about genetic testing. One of the most commonly cited fears is that the results will affect the ability to obtain or keep affordable health insurance (Lawrence and Appelbaum, 2011). Worries about employment discrimination are also common.
Recent clinical studies of naltrexone have demonstrated the potential importance of genotyping as a predictor of treatment response (Oslin et al., 2003; Anton, 2008). Of particular interest is the µ-receptor, which has been linked to the brain reward areas and increases in reinforcement to drinking alcohol, albeit inconsistently (Rouvinen-Lagerstrom et al., 2013). In addition to the opioid system, it has long been known that variations in alcohol metabolism are associated with different levels of risk of an AUD yet this knowledge is rarely applied to clinical practice (Eriksson, 2001; Cook et al., 2005; Wall et al., 2005). Additionally, polymorphisms found in the µ-receptor, OPRM1, specifically the A+118G (Asn40Asp) have been linked to significantly better treatment response to naltrexone (Oslin et al., 2003; Anton et al., 2008; Thorsell, 2013).
If genotype does predict response to a medication like naltrexone, then screening patients' genotype may target naltrexone therapy to patients who are most likely to respond to this therapy, thereby improving efficiency in healthcare delivery. However, in this vulnerable AUD patient population, it is unknown whether patients would accept genetic testing. Without patient acceptance, the implementation of widespread genetic testing for naltrexone therapy for AUD would be hindered, regardless of the positive treatment effect that naltrexone would provide.
We sought to explore the patient perceived barriers or concerns to genetic testing among a treatment-seeking sample of individuals with an AUD. We hypothesized that patients with an AUD would be mostly concerned with issues related to privacy and implications for insurance mirroring findings in studies from other clinical samples. We further hypothesized that patients would be less aware of genetics as important to addiction, in comparison with other common disorders. We surveyed individuals from two geographically and clinically distinct treatment populations. One group was participating in a randomized clinical trial of naltrexone specifically designed to study the relationship between genotype and clinical response, while the other sample was from a residential treatment facility of individuals being treated for alcohol dependence with and without the use of naltrexone.
METHODS
Subjects
Alcohol-dependent participants (n = 483) were recruited from two different clinical research studies focused on the use of naltrexone as a treatment option. Eligible participants in both studies were at least 18 years old and met DSM-IVTR criteria for current alcohol dependence. All participants were seeking treatment for their AUD. Subjects were excluded if they demonstrated current abuse or dependence on illicit drugs or opioids, exhibited signs of dementia, psychosis or mania, or were actively engaged in standard addiction outpatient specialty care. There were no exclusions for depression or anxiety disorders; however, in Study 1 participants could not be taking a psychotropic medication. Both studies were reviewed and approved by the Institutional Review Board of the respective sites and all subjects provided written informed consent prior to study participation.
Study 1 includes 168 individuals who were recruited to participate in a treatment study of naltrexone. All participants were required to provide a DNA sample for genetic testing in order to participate in the study. In addition to the above criteria, patients had to be of Caucasian or Asian descent. Study 2 (n = 315) includes consented potential participants for a case matched control study of patients treated clinically with naltrexone and a matched control group of patients who were not treated with naltrexone or any other medication specifically for alcohol dependence. Participants from the second trial were recruited from a residential treatment facility. There were no exclusions based on race.
Assessment instruments
All assessments for this project were conducted at the beginning of the study by a trained research assistant. Assessments measured amount of drinking, severity of alcohol problems and psychosocial functioning. The primary measure of drinking outcome was the Time Line Follow-Back (TLFB) (Sobell et al., 1988; Sobell and Sobell, 1992). Quantity of alcohol was recorded in standard drinks. Heavy drinking was defined as five or more drinks in a single day for men, four or more for women (Volpicelli et al., 1992; Anton, 1996; Kranzler et al., 2001). Additional outcome assessments included the Short Inventory of Problems (SIP) (Miller et al., 1995), the Medical Outcomes Study Short Form – 12 (MOS SF-12) (Ware et al., 1996) and demographic information.
The survey on genetics was a non-standardized self-assessment. The questionnaire was divided into sections that asked the respondent to gauge the degree to which they thought common health disorders were inherited, to rate the degree to which genetic testing might be useful to family planning or clinical care, and finally to rate concerns about genetic testing. All ratings were done using a Likert scale ranging from 1 (the greatest rating) to 5 (the lowest rating). Participants were asked to rate how much they agreed or disagreed that the following diseases can be inherited (or have a genetic predisposition): hypertension, Down's syndrome, colon cancer, Alzheimer's disease, drug dependence, depression, alcoholism, heart disease and breast cancer. They were then asked to rate how willing they would be to have their DNA tested to help with treatment planning, using a Likert scale ranging from 1 (very willing) to 5 (not at all willing). Participants were then asked ‘How worried are you that providing DNA to your clinician might be used for the following purposes?’ A Likert scale was again used ranging from 1 (very worried) to 5 (not at all worried) on all of these areas: steal your identity (privacy concerns); deny employment; deny life insurance; deny health insurance; clone body parts; as part of a criminal investigation; parental testing; discrimination. The next question asked, ‘In your opinion, did either your mother or father have an alcohol or substance abuse problem?’ Participants can answer either ‘no,’ ‘yes,’ or ‘don't know.’
Statistical analysis
Variables were compared using Chi-square tests for categorical variables and Wilcoxon tests for continuous variables. To compare genetic attitudes between the common health disorders while controlling for within subject correlated responses, generalized estimating equation (GEE) methods were applied to model attitude based on disorder. Both exchangeable and unstructured correlation matrix structures were explored; results were not notably different. Bonferroni corrections were applied to adjust for multiple comparisons.
RESULTS
Genetic testing was not required for participation in Study 2, however; only 14 subjects (4%) did not consent to providing DNA. For Study 1, genetic testing was required but there were no reports of subjects refusing to consent because of the genetic requirement. There were 483 subjects who completed the survey. Of the 483 surveys, 5 subjects endorsed the same response column on 35 or more out of the total 41 items and 21 subjects were missing a substantial number of responses (19+); these subjects were excluded from the analysis leaving 457 in the analytic sample. The sample was predominately Caucasian (97%) and of non-Hispanic ethnicity (98%). About half of the participants were married and 38% were female with a mean age of 45 ± 12. The participants reported an average of 23.8 ± 10.0 alcohol-related problems, and drank on 73% of days with 57% of days being heavy drinking. Their overall mental health quality of function as rated by the SF-12 was 36 ± 13 indicating poor function. Differences between participants in the two studies were the presence of more men in Study 1 (P < 0.001) and more married individuals in Study 2 (P = 0.002). Study 1 participants were also older and had better quality of functioning, fewer alcohol-related problems and more drinking (P < 0.001).
The majority of respondents (89%) reported a willingness to provide genetic samples for clinical purposes related to the treatment of an AUD. Consistent with this rating in study 2 in which the genetic sample was not required for participation, only 4% of the participants declined to provide a sample for research purposes. While there were few non-white participants, non-white participants were significantly less likely to report a willingness to participate in providing DNA for clinical purposes (OR 5.6 95% CI: 1.7–17.7, P = 0.004). No other demographic or clinical characteristics predicted a response to this question. Participants were also willing to provide DNA for other disorders such as colon cancer, hypertension, Down's syndrome, depression, heart disease and Alzheimer's disorder (all >77%).
The main areas of concern related to genetic testing were focused on denial of health or life insurance. Overall 35% of respondents were worried or very worried that genetic testing done in a physician's office might lead to denial of health insurance, and 32% felt the same about life insurance. No demographic or clinical characteristics predicted a worry over life or health insurance. Twenty-one percent worried that the testing would impact employment and 15% worried about identity theft. There were fewer participants concerned about cloning (13%), legal issues (14%) or paternity issues (8%). Only concerns about parental issues differed between the two study samples, with more worried subjects in Study 2 (5 vs 10%, P = 0.04).
In regard to the heritability of alcohol dependence, 83% of the respondents agreed or strongly agreed that an AUD was at least partly inherited. Of note, 54% reported that they believe either their mother or father drinked excessively. Participants also considered other disorders such as depression, heart disease and Alzheimer's disorder as having a genetic component (all >65%). Down's syndrome was found to have the lowest rate of subjects agreeing or strongly agreeing that it was inheritable (48%), but this was driven mostly by a rating of undecided (22%). An AUD was more likely to be rated as being inheritable compared with each of the other diseases (all OR > 1.8, adjusted P < 0.001), except heart disease (OR = 1.06, 95% CI = (0.82, 1.38)).
DISCUSSION
The results of the survey confirmed that patients have significant concerns about providing DNA for genetic testing. Consistent with previous surveys of patients, these concerns focused mostly on insurance and employment. These results underscore the importance of informed consent and discussions about access to the testing results and any potentially stored DNA samples. Healthcare providers will need to take on this role as genetic testing is introduced into clinical settings. It was demonstrated in the study sample that patients properly informed and assured as to the confidentiality of testing would be willing to provide samples despite their concerns. Unexpectedly, the participants rated the heritability of an AUD as high as or higher than some other common disorders. We included Down's syndrome in the scale as a disease widely known to be genetic. However, nearly a quarter of the sample appeared not to be familiar with Down's syndrome or be aware of the genetic nature of the disease.
There are significant limitations to interpreting the results of this survey. Most notably was the very low participation rate of minorities. This is understandable in Study 1 as African-American minorities were excluded due to the very low rate of occurrence of the G allele at the A118G SNP. Thus it is unclear if concerns or perceptions would differ in minority populations though there is a significant association with minority status and willingness to provide DNA. Despite the low number of minority participants, this finding is consistent with a finding from the VA Cooperative study of naltrexone which had fewer minority subjects contribute DNA samples to the study than Caucasian participants (Gelernter et al., 2007). Therefore, an important future direction may include examining attitudes within minority populations and patients not participating in a research study that is focused on genetics. The second notable issue was that both of these studies addressed genotyping and inheritability in the consent process. The consent process should have provided some education and alleviated concerns prior to answering the survey, and therefore it is unclear whether the process influenced participants' answers. Finally, we are unable to know whether individuals did not participate in Study 1 because of the focus on genetics. In study 2, only 4% of participants refused to provide DNA for research purposes even though this was not a requirement for participation. Despite these limitations, a strength of the study is the consistency of findings across two very different studies and populations suggesting that the results are generalizable to at least Caucasian treatment-seeking individuals.
In summary, individuals with an AUD appear to be ready for genetic testing to be introduced into the clinical setting. The patients in these two studies demonstrated a high degree of sophistication regarding their understanding of the need for testing and the risks. However, as genetic testing is introduced into clinical settings, it will be vital that healthcare providers become fluent in the risks and concerns of their patients so that these concerns can be identified and discussed for each individual.
Author Contributions
D.O., C.O., W.B. and F.B. participated in the design of the study and wrote the protocol. S.L. undertook the statistical analysis, and D.O., B.S. and L.M. wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.
Funding
Funding for this study was provided by NIAAA Grant AA017164; funding support was also provided by the Department of Veteran Affairs by the center grant for the VISN 4 Mental Illness Research, Education, and Clinical Center at the Philadelphia VA Medical Center. Funding was also provided from the Huss Family through a generous donation to the Hazelden foundation. None of the funding sources had a role in study design; in the collection, analysis and interpretation of data; in the writing of the report or in the decision to submit the paper for publication.
Conflict of interest statement. None declared.