Genetic Testing and Privacy: Are Our Health Care Policies Adequate?

As a genetics professional who provides genetic testing, I am aware of the fact that many individuals contemplating genetic testing cite insurance and employment concerns as major reasons to forego testing. For that reason, I heaved a sigh of relief on May 21, 2008 when the Genetic Information Non-Discrimination Act (GINA) was signed in to law. First introduced in 1995, at a time when only about 300 genetic tests were currently in use and these for mainly rare diseases, it was called both forward-thinking and premature. Now hailed as the first civil rights law of the new century, GINA will prohibit group and individual health insurers from using a person’s genetic information in determining eligibility or premiums and prohibit employers from using a person’s genetic information in making employment decisions such as hiring, firing, job assignment, or other terms of employment. Guidelines for segregating genetic information from other medical records are expected to be forthcoming.

As I thought more about it, however, I realized that the world has changed rapidly in the 14 years since this bill was first introduced, and that these changes may well undermine the protections that GINA was meant to provide. I see four main threats: 1) more genetic information everywhere, 2) data expansion, 3) genome wide association studies, and 4) electronic medical records.

Under the more information heading, the terms “Genetic information” and “genetic condition” are becoming more difficult to define. We are finding that almost all illness has some genetic component such that making clear distinctions between genetic and non-genetic health information is becoming increasingly meaningless. Under the data expansion category, genetic research has shifted from diseases linked to a single gene (Huntington disease, cystic fibrosis) to more common and complex illnesses characterized by the interactions of multiple genes and environmental factors (asthma, diabetes). There are now over 1500 genetic tests in use and in the not-so-distant future, nearly all health records will include substantial genetic information. Genome Wide Association Studies (GWAS) look for single changes in the hundreds of thousands of base pairs (A,T,C,G) that make up the human genome associated with a particular illness or condition. These conditions may be as serious as breast cancer or as frivolous as what type of ear wax you are prone to develop. These tests are being aggressively marketed directly to consumers and can be ordered on line for less than $400. There is little oversight of the companies marketing these tests and as one who works in the field of genetics, it seems almost criminal to test for one mutation associated with cystic fibrosis out of the more than 1000 known CF mutations and call that information useful in the absence of extensive educational efforts. It may not be long before our patients come to our offices with their printouts from 23&Me and ask to add them to their medical record. The fourth threat may be the shift from paper-based medical records to electronic health records (EHR) with their goal of standardization, compatibility, and ease of transport. In a paper-based system, the greatest protection of individual privacy is chaos, the inability to aggregate a complete record from multiple providers over time. Comprehensive and longitudinal medical records will inevitably contain sensitive information and patients will no longer have the option of selective recall in the sense of “is that depressive episode I experienced in graduate school after being mugged really relevant information for the orthopedist performing my knee surgery twenty years later?” Electronic medical records will make it even more difficult to sequester genetic information.

One other developing trend may also play a role, the refinement of personalized medicine, the ability to target drug therapies customized to each person’s genetic makeup to both improve the effectiveness of current treatments and to reduce side effects. Pharmacogenetic testing is becoming standard practice in selecting drugs and dosages for certain cancers while toxicogenetics, the use of GWAS studies to predict how individuals may respond to certain toxins, is becoming more important in assessing both individual and public health risks. If genetic factors appear to play a role in individual and/or community resistance to flu viruses, who knows what might happen.

Technology moves rapidly while our legislature does not. A bill introduced to fix a problem in 1995 may not be as relevant or as useful in 2009. So while I am still happy that GINA was finally passed, the devil, as they say, is in the details, and it remains to be seen how much protection is actually provided for our patients and their families.

Kimberly A. Quaid, Ph.D.

Long Term Outcomes of Presymptomatic Testing in Huntington Disease

Huntington disease (HD) is a late onset autosomal dominant neuropsychiatric disorder. Symptoms include a movement disorder, mood disturbances and dementia. The average age of onset is approximately 40 years of age and if one of your parents is affected with the disease, you have a 50% chance of having inherited the genetic mutation that causes HD. Men and woman are equally affected.

In 1993, the genetic mutation that causes Huntington Disease was discovered. This discovery meant that direct genetic testing for the presence or absence of the HD mutation could be offered. Testing is usually offered within a multidisciplinary framework including geneticists, neurologists, psychologists, nurses and social workers and within a testing protocol that involves a neurological examination, pretest counseling, results in person and available follow-up. Estimates indicate that in Europe, less than 20% of individuals at risk for HD takes the test. Estimates for the United States suggest that the uptake of testing is even lower. The lack of a cure for HD, or a treatment that can delay the onset or slow the progression of the disease, is likely a major factor in the low uptake of testing.

Recently, in some HD circles, there have been calls to increase the number of individuals getting tested in order to have a cohort of gene positive individuals ready to participate in future clinical trials. This desire to increase the number of individuals tested is, in my opinion, wrong headed for many reasons, but a recent paper on the long term effects of testing also suggests that caution is in order.

In February of 2009, the European Journal of Human Genetics published a paper examining the long term impact of presymptomatic testing for Huntington disease. The authors interviewed 119 (57 gene carriers and 63 non-carriers) asymptomatic individuals after an average delay of 3.7 years after they received their genetic test result. The main outcomes of interest in the paper were social and psychological adjustment after testing (1).

The results were as follows: The overall scores for social adjustment were similar in carriers and non-carriers and were in the normal range for both groups. Carriers were not more anxious than non-carriers, but current depression was significantly more frequent in the carriers. Prior to testing, there were no differences in the number of carriers and non-carriers who had experienced a depressive episode. After testing, however, the percentage of carriers experiencing depression rose from 42% to 49% while the percentage of non-carriers experiencing depression fell from 45% to 31%. Perhaps even more important is the fact that carriers had significantly higher scores than non-carriers when evaluated with the Beck Hopelessness Scale, considered to be a measure of suicidality. Of note is the fact that while there was one suicide attempt and one hospitalization for major depression after testing in the carrier group, three non-carriers also attempted suicide, one was hospitalized for depression and one hospitalized for a psychotic episode. Despite this evident distress, only 31% of the carriers and 15% of the non-carriers were under psychiatric care and only 36% of the carriers and 15% of the non-carriers were under treatment with antidepressant or anti-anxiety medications. Further investigation indicated that the best predictor for the occurrence of depression after taking the test was the presence of a previous depressive episode. In other words, individuals who have experienced depression prior to testing are more likely to experience depression after testing. Finally, when asked to rate the current impact of the test results on their lives, carriers gave a more negative rating than non-carriers and reported that they had less ability to cope with the test results than non-carriers. Again, it is important to note that more than 25% of the non-carriers reported difficulty coping with the test result.

It is possible to compare these results with a previous study looking at long term outcomes 7-10 years after testing (2). This study of 142 tested individuals and their partners found that carriers and their partners were more distressed immediately after the test. Their outlook appeared to improve somewhat in the 2-3 year post test period but became more negative as the age of onset approached. This study also found that carriers who were lost to follow-up reported more pretest distress than did those carriers who participated in the follow-up study. This finding, which reflects both my own experience and the anecdotal experience of other test center directors, is important because it suggests that most studies examining the impact of testing may tend to underestimate the amount of distress that is being experienced by those who have been tested.

So what do these results tell us? In the 2009 study, almost half of the carriers where experiencing depression after testing. However, almost a third of non-carriers were also experiencing depression. At least two studies have suggested that it might take up to five years for non-carriers to experience a positive change in their quality of life after receiving a favorable test result (3,4). One explanation that has been given is that it takes this long to resolve the emotional state of mourning for the loss of being at risk and the end of doubt about one’s genetic status. Others have hypothesized that that non-carriers may be experiencing 1) survivor guilt for not having the HD gene when others in the family might 2) regret for life decisions made in the past as a function of being at risk, 3) inability to leave behind the at risk mind set, 4) inability to truly believe the test results, and 5) negative reactions on the part of family members (1).

Whatever the explanation, these results indicate that individuals at risk, carriers and non-carriers alike, may be a vulnerable population and that it is particularly important to assess and treat depression before testing and to provide psychological support and psychiatric care after testing. These results also suggest that the decision to be tested should not be made lightly and that the impact of testing may last a long time after results are given.
References:

1. Gargiulo M, Lejeune S, Tanguy ML et al, (2009). Long-term outcome of presymptomatic testing in Huntington disease. European Journal of Human Genetics, 17:165-171.

2. Timman R, Roos R, Maat-Kievet A, and Tibben A. (2004) Adverse effects of predictive testing for Huntington Disease underestimated: Long term effects 7-10 years after the test. Health Psychology 23:189-197.

3. Decruyenaere M, Evers-Kiebooms G, Cloostermans T et al. (2003) Psychological distress in the 5-year period after predictive testing for Huntington disease. European Journal of Human Genetics 11:30-38.

4. Almqvist EW, Brinkman RR, Wiggins S, Hayden MR (2003) Psychological consequences and predictors of adverse events in the first 5 years after predictive testing for Huntington disease. Clinical Genetics 64: 300-309.

Kimberly A. Quaid, PhD

Genetic Privacy: T.J. Maxx and the NIH

What do T.J. Maxx, the V.A. and NIH have in common? They have all been involved in handling personal data in such a way that individual privacy and confidentiality may have been violated. In December 2006 the financial information of over 40 million customers of T.J. Maxx and Marshall’s was accessed by a hacker potentially exposing customers to identity theft. Also in 2006, a laptop computer containing personal information including names, addresses, dates of birth and social security numbers for 38,000 veterans went missing. This past August, large amounts of aggregate human DNA data that the National Institute of Health and other groups had made open to researchers around the world was removed from public view due to privacy concerns. The reason behind this removal was a study (doi:10.1371/journal.pgen.1000167) released by the Translational Genomics Research Institute and the University of California showing that using an algorithm and a microarray a curious individual could possibly identify whether or not an individual’s DNA was in a genome wide association study (GWAS) database.

Why does this matter? NIH and other groups conducting GWA studies know that one of the core ethical components of their work, and a critical element for convincing people to participate in these studies, is being able to promise that their personal medical and genetic information will not be compromised and will never be used in such a way that might cause them harm. Being able to demonstrate, for example, that a representative of law enforcement armed with a DNA sample from a crime scene could search an existing NIH database for a sample match and be successful, undermines this promise in a way that might give us all pause. Researchers will still have access to the data, but they will now have to apply for access to the data and agree to protect the confidentiality of the data.

As researchers strive to use the information gained by the Human Genome Project for the improvement of health care and the prevention and treatment of disease, more and more of us will be asked to participate in efforts to establish enormous databases of our genotypic (DNA) and phenotypic (medical records) information. I still shop at Marshall’s, but I am not sure I will be giving my DNA anytime soon. --Kimberly A. Quaid

Weighing Hope: Living at Risk for Huntington Disease

If you had a parent with Huntington Disease, you would have a 50:50 chance of also having the disease. That's a very high risk - flip a coin - for a disease that has no cure. To make matters worse, the risk itself could strain relationships, lead to social stigmatization and even discrimination. So, if you were at risk for the disease, but had thus far declined a diagnostic, genetic test, would you tell your co-workers, friends and family members about your risks?

Before assuming that you would share news of this risk with all the important people in your life, you might want to read a recent publication by lead author Kimberly A. Quaid, a PredictER team member. In "Living at risk: concealing risk and preserving hope in Huntington Disease" (Quaid KA, Sims SL, Swenson MM, et al. J Genet Couns. 2008 Feb;17(1):117-28. Epub 2007 Oct 18. PMID: 17943424), Quaid et al report the results of open-ended, qualitative interviews of 55 individuals at risk for the disease. Although research on the psycho-social impact of living with the knowledge of genetic risk for Huntington Disease often focuses on the decision of whether or not to be tested and/or whether or not to share the test result, this paper is unique in that it examines: 1) the decisions of those who have not received a genetic test and 2) the ongoing, daily decisions to both disclose and conceal this risk information. After reviewing the unstructured interviews, the authors conclude that some people chose to conceal their risks for many valid reasons, including: to protect themselves from discrimination, to identify the best circumstances in which to share the information with loved ones (especially young children) and to preserve personal hope that they will not succumb to the disease. Quaid et al also remind us that: "Choosing to be tested is, in a way, a decision to disclose one's real risk to oneself. Participants' choosing not to be tested is not denial but a positive way to preserve both hope and their identities as people with a future". The authors encourage clinicians to respect a patient's desire not to be tested. For some patients a genetic test for an incurable disease will not provide helpful information; in fact, for some, the "knowledge … of HD may serve to destroy hope".