Beyond the patient The broader impact of genetic discrimination among individuals at risk of Huntington disease.код для вставкиСкачать
RESEARCH ARTICLE Neuropsychiatric Genetics Beyond the Patient: The Broader Impact of Genetic Discrimination Among Individuals at Risk of Huntington Disease Yvonne Bombard,1,2,3† JoAnne Palin,1† Jan M. Friedman,4 Gerry Veenstra,5 Susan Creighton,4 Joan L. Bottorff,6 Michael R. Hayden1* and The Canadian Respond-HD Collaborative Research Group‡ 1 Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada 2 Yale University, Department of Epidemiology and Public Health (Division of Health Policy and Administration), New Haven, Connecticut 3 Memorial Sloan Kettering Cancer Center, Center for Health Policy and Outcomes, New York, New York Children’s & Women’s Hospital of British Columbia, Vancouver, British Columbia, Canada 4 5 Department of Sociology, University of British Columbia, Vancouver, British Columbia, Canada 6 Faculty of Health and Social Development, University of British Columbia Okanagan, Kelowna, British Columbia, Canada Received 25 July 2011; Accepted 7 December 2011 We aimed to address gaps in current understanding of the scope and impact of discrimination, by examining a cohort of individuals at-risk for Huntington disease (HD), to describe the prevalence of concern for oneself and one’s family in multiple domains; strategies used to mitigate discrimination; and the extent to which concerns relate to experiences. We conducted a cross-sectional survey of 293 individuals at-risk for HD (80% response rate); 167 respondents were genetically tested and 66 were not. Fear of discrimination was widespread (86%), particularly in the insurance, family and social settings. Approximately half of concerned individuals experienced discrimination (40–62%, depending on genetic status). Concern was associated with ‘‘keeping quiet’’ about one’s risk of HD or ‘‘taking action to avoid’’ discrimination. Importantly, concern was highly distressing for some respondents (21% for oneself; 32% for relatives). Overall, concerned respondents with high education levels, who discovered their family history at a younger age, and those who were mutation-positive were more likely to report experiences of discrimination than others who were concerned. Concerns were rarely attributed to genetic test results alone. Concern about genetic discrimination is frequent among individuals at-risk of HD and spans many settings. It inﬂuences behavioral patterns and can result in high levels of self-rated distress, highlighting the need for practice and policy interventions. Ó 2012 Wiley Periodicals, Inc. Key words: genetic discrimination; stigma; concern; self-rated distress; Huntington disease; families INTRODUCTION Despite accelerating advances in genomic technology and individualized disease prevention, uptake rates for genetic testing still lag [Hadley et al., 2003; Hayden and Bombard, 2005; Meiser et al., Ó 2012 Wiley Periodicals, Inc. How to Cite this Article: Bombard Y, Palin J, Friedman JM, Veenstra G, Creighton S, Bottorff JL, Hayden MR, The Canadian Respond-HD Collaborative Research Group. 2012. Beyond the Patient: The Broader Impact of Genetic Discrimination Among Individuals at Risk of Huntington Disease. Am J Med Genet Part B 159B:217–226. Additional Supporting Information may be found in the online version of this article. Disclosures: All authors report no conﬂicts of interest, as per AJOB policy. † Yvonne Bombard and JoAnne Palin contributed equally to this article. ‡ The members of the Canadian Respond-HD collaborative research group are: Mark Guttman & Christine Giambattista, Centre for Movement Disorders; Mark Ludman, Jill Murphy & Tina Babineau-Sturk, IWK Health Centre; Patrick MacLeod & Jennifer Rice, Victoria General Hospital; Wayne Martin & Marguerite Wieler, University of Alberta; Wendy Meschino & Clare Gibbons, North York General Hospital; Lynn Raymond & Joji Decolongon, University of British Columbia; Oksana Suchowersky & Mary-Lou Klimek, University of Calgary. Grant sponsor: Canadian Institutes of Health Research. *Correspondence to: Dr. Michael R. Hayden, MB, ChB, PhD, FRCP(C), FRSC, Department of Medical Genetics, Centre for Molecular Medicine & Therapeutics, Child & Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4. E-mail: firstname.lastname@example.org Published online 9 January 2012 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ajmg.b.32016 217 218 2006] There are numerous reasons that may account for this including, high costs, uncertain clinical utility, limited health care capacity, and lack of evidence for beneﬁt. One reason that has been the focus of considerable attention is the concern for the possibility of genetic discrimination [Kinney et al., 2001; Hadley et al., 2003; Warner et al., 2005; Lewis and Peterson, 2007; Robson et al., 2010]. Genetic discrimination (GD) refers to the differential treatment of asymptomatic individuals or their family members based on real or presumed genotype [Billings et al., 1992]. Concerns about the possibility of discrimination have centered on the misuse of genetic information to unfairly deny opportunities based on real or presumed risks of becoming ill in the future. Apprehension has typically focused on the insurance and employment sectors, where individuals have been particularly concerned that insurers will use their genetic information to impose high premiums or deny coverage [Bombard and Lemmens, 2010]. Besides the possibility of accessing available genetic test results, individuals are also concerned that insurers may request that an applicant undergo genetic testing in order to qualify for an insurance policy [Bombard et al., 2007]. Pressure to take a genetic test can result in unsolicited information about one’s genetic risks that may cause psychosocial burden and distress, and infringe on genetic privacy, raising ethical concerns [Laurie, 1999; Andorno, 2004]. Huntington disease (HD) has always been a particular target of social stigma and discrimination. From the ‘‘Dancing Mania’’ of the Middle Ages to the ‘‘Witchcraft Disease’’ during the eugenics movement, HD has been veiled under shrouds of secrecy for decades [Wexler, 2010]. However, recent discourse has suggested that stigma and the fear of discrimination have contributed to inaccurate estimates of the true prevalence of HD, which has adversely affected research and clinical supports for HD families [Anonymous, 2010; Rawlins, 2010]. This represents a signiﬁcant ethical and social concern because without knowledge of its true prevalence [Morrison et al., 2011], appropriate services and efﬁcacy of prophylactic treatments are unlikely to be established. However, accurately estimating the prevalence of HD requires an appreciation of the nature and extent of stigma and fear of discrimination. Studies of stigma and fear of discrimination have thus far focused on small, symptomatic or genetically tested samples [Wingrove et al., 1996; Lynch et al., 1997; Peterson et al., 2002; Armstrong et al., 2003; Apse et al., 2004; Hall et al., 2005; Warner et al., 2005; Bombard et al., 2008]. Thus, reports of stigma and fear of discrimination have been hampered by conﬂation of discrimination based on symptoms and genetic discrimination, which is the differential treatment of asymptomatic individuals or their family members based on real or presumed genotype [Billings et al., 1992]. While both forms of discrimination likely inﬂuence stigma and fears of discrimination, it is fear of genetic discrimination that has caused family members to conceal their family histories and genetic test results, which has contributed to inaccurate estimates of the prevalence of HD [Bombard et al., 2007; Anonymous, 2010]. There is a paucity of evidence about the range of situations in which individuals fear discrimination (such as health care, insurance, employment, relationships, etc.), the prevalence of concern (lifetime and recent), the level of distress caused by their concerns, how their fears about discrimination relate to their experiences of it, the range of situations in which individuals fear discrimination AMERICAN JOURNAL OF MEDICAL GENETICS PART B towards relatives, and the strategies they use to address ‘‘anticipated discrimination’’ [Thornicroft et al., 2009]. The ramiﬁcations of concern for discrimination are particularly troubling because they create barriers to services that may offer important therapeutic or management opportunities. Understanding the nature and extent of these concerns is important to cultivate open communication between patients and their health care providers, and develop appropriate interventions to reduce stigma and ascertain true disease prevalence, which will ultimately serve to beneﬁt public health. We conducted a study among individuals atrisk for HD to examine the nature and prevalence of concern for discrimination towards oneself and one’s family members, to describe strategies individuals use to mitigate discrimination, to explore how concerns for discrimination relate to experiences of discrimination, and to identify factors associated with experiences and concerns of genetic discrimination. METHODS Study Design and Sample We conducted a self-administered survey at seven Canadian clinics, targeting 300 asymptomatic adults (Uniﬁed HD Rating Scale score (UHDRS) < 2 [Bombard et al., 2009]) who had a family history of HD. We received approval from relevant ethics boards and patients’ consent was received prior to questionnaire completion. The survey methods and questionnaire design have been described elsewhere [Bombard et al., 2009]; we developed the content using qualitative studies [Bombard et al., 2007, 2008; Penziner et al., 2008] and validated discrimination instruments [Krieger et al., 2005; Taylor et al., 2008]. The deﬁnition of discrimination used in our study is consistent with validated deﬁnitions of ‘‘discrimination’’ [Krieger et al., 1998, 2005; Kessler et al., 1999; Borrell et al., 2007], and of ‘‘genetic discrimination’’ speciﬁcally [Taylor et al., 2008], and based on deﬁnitions developed through preceding qualitative research [Bombard et al., 2008]. Measures We asked respondents when they ﬁrst became aware that HD was in their family and when they had been genetically tested. We veriﬁed their genetic status through medical records. The most common interpretation of discrimination provided by participants in a preceding qualitative study was ‘‘being unfairly prevented from doing something, or being treated unfairly’’ [Bombard et al., 2008]. This characterization was used in the survey and is consistent with established deﬁnitions of discrimination [Krieger et al., 2005; Borrell et al., 2007; Taylor et al., 2008]. To assess concern about discrimination, we asked if respondents ever worried about being treated unfairly because of their family history and/or genetic test result in each of 23 possible situations. If they responded ‘‘yes’’ to any of the situations, respondents were classiﬁed as having had concern for themselves, as depicted in Supplementary Appendix A. To facilitate analyses with adequate sample sizes, we grouped the 23 situations into six settings (Table I). Similarly, we asked respondents if they had ever worried about relatives experiencing discrimination in those situations. Finally, we asked if respondents had ever experienced genetic discrimination. BOMBARD ET AL. 219 TABLE I. Concerns About Genetic Discrimination a Setting/Item Overall Insurance By a life insurance company or agent By a long-term disability company or agent By a mortgage company or agent Family When making choices about having children By your spouse By a member of your family Social When establishing a relationship By your community By a boy/girlfriend By a friend At school By your religious organization Employment At work When getting hired or getting a job Health care When getting medical care By other health care professional(s) By your doctor By a genetic counseling service Public sector By an adoption agency In the law courts By a blood bank When getting access or custody to your children By the Canadian Forces Self b n (%) 175 (75.1) Familyb n (%) 171 (73.4) 141 (60.5) 124 (53.2) 58 (24.9) 117 (50.2) 115 (49.4) 76 (32.6) 84 (36.1) 40 (17.2) 32 (13.7) 95 (40.8) 33 (14.2) 37 (15.9) 88 (37.8) 42 (18.0) 37 (15.9) 36 (15.5) 11 (4.7) 4 (1.7) 106 (45.5) 49 (21.0) 59 (25.3) 46 (19.7) 22 (9.4) 11 (4.7) 72 (30.9) 65 (27.9) 77 (33.0) 81 (34.8) 46 (19.7) 25 (10.7) 16 (6.9) 9 (3.9) 60 (25.8) 36 (15.5) 25 (10.7) 14 (6.0) 26 (11.2) 24 (10.3) 24 (10.3) 19 (8.2) 7 (3.0) 20 (8.6) 37 (15.9) 23 (9.9) 34 (14.6) 14 (6.0) a Respondents selected all that applied. Number and percentage of respondents reporting ‘‘yes,’’ they have been concerned about discrimination as a result of either or both their family history and genetic test result. b We also asked respondents to rate the level of concern and the degree of distress their concern caused them on scales from 1 to 5, regarding their family history and genetic test result. Similarly, we asked respondents to rate their levels of distress and concern about discrimination for family members, due to the family history or the respondent’s genetic test result. We asked respondents who reported that they had ever worried about genetic discrimination how much they worried about being treated unfairly because of their family history or genetic test result in the past year: ‘‘rarely or never,’’ ‘‘some of the time,’’ or ‘‘most of the time.’’ We classiﬁed those who responded ‘‘some of the time’’ or ‘‘most of the time’’ as having been concerned in the past year. We also asked how much they worried about genetic discrimination towards family members in the past year, due to the family history or the family members’ genetic test results (Supplementary Appendix A). Based on preceding qualitative research in this sample and strategies developed in established discrimination surveys [Krieger t al., 2005; Bombard et al., 2007], we asked respondents to indicate which general strategies they used when faced with the possibility of discrimination. Statistical Analysis We used chi-square and Fisher’s exact tests for comparisons by group and by setting, as applicable. In order to assess factors associated with ‘‘concern only’’ versus ‘‘concern and experience,’’ we evaluated demographic characteristics (age, sex, marital status, having children or not, highest level of education, income, employment status, urban/rural residence) and genetic information (age when family history of HD was learned, years since learning of the family history of HD, genetic test status) in univariate logistic regression analyses that included all settings combined. We added all variables with P < 0.10 into multivariable models for all settings combined and by setting. The family/social settings, and ‘‘other’’ (i.e., employment, health care, public sector) settings, were grouped due to small sample sizes. We dichotomized the age of learning one’s family history 220 AMERICAN JOURNAL OF MEDICAL GENETICS PART B at the median (25 years) for ease of interpretation and because the results were similar whether this age was entered in categorical or continuous form. We used SPSS 18.0.0 (SPSS Inc., Chicago, IL). RESULTS Study Participants Of 299 individuals who were invited to participate in the survey, 239 (79.9%) responded, and six were excluded because they had UHDRS scores >2 before completing the survey questionnaire. There were no signiﬁcant differences in the characteristics of the respondents across test status categories nor between responders and non-responders with respect to being tested or not (P ¼ 0.334), by positive or negative mutation status (P ¼ 0.365), age (P ¼ 0.077), or gender (P ¼ 0.206). While the characteristics of participants in our sample are similar to those of participants in other HD studies, our study sample appears more educated and older [Wiggins et al., 1992; Almqvist et al., 2003]. The characteristics of the sample have been described elsewhere [Bombard et al., 2009, 2010]. Prevalence of Concern About Genetic Discrimination Eighty-six percent (86%) of respondents reported being concerned about genetic discrimination towards themselves or their family members at some point in their lifetime. Three-quarters (n ¼ 175) had concern for themselves, and 73% (n ¼ 171) had concerns about family members (Table I). Most (63%) had concerns for both self and family (Fig. 1). Insurance * 18 10 45 14 18 Family 13 Social † 30 21 32 15 19 23 Employment 12 12 Health care 9 Public sector Self (only) Family (only) Both (self AND family) 17 8 Overall concern about GD -- past year † 0 Reasons for Concern (Family History and/or Genetic Test Result) Few respondents attributed their concern to their genetic test result alone. Of the 125 tested respondents who had ever had concern, 74 (59.2%) attributed their concern to both their family history and genetic test result, while 48 (38.4%) ascribed their concern to their family history only, and three (2.4%) reported that they had ever had concern about being treated unfairly due to their genetic test result alone (P < 0.001). Of the 65 respondents with the HD mutation who reported that they had ever had concern for themselves, 80.0% attributed their concern to both their family history and mutation status, followed by their family history only (18.5%), or their mutation status only (1.5%; P < 0.001). The 127 tested respondents who had concern for family members mainly attributed their concern to their family history only (59.8%), followed by their family history and genetic test result (37.8%), and 2.4% to their genetic test result alone (P < 0.001). Mutation positive respondents attributed their concern for family members to their family history only (49.2%), or their family history and mutationstatus (47.7%), followed by their mutation status alone (3.1%; P < 0.005). 15 14 12 11 Overall concern about GD -- ever Concern by setting. The prevalence of concern for family was 8% higher for family than self in the social setting (13% for self only vs. 21% for family only), and 8% lower for family than self in the insurance setting (18% vs. 10%) (Fig. 1). Concern in the past year. There were 138 respondents who reported concern for either themselves or family members ‘‘some’’ or ‘‘most of the time’’ in the past year (of whom 26% (n ¼ 36) felt concern ‘‘most of the time’’ in the past year). Within the past year, the prevalence of concern for family was 19% higher than concern for themselves: 27% had concern for family (only), 8% had concern for themselves (only), and 24% for both family and themselves (Fig. 1). Concern and genetic test status. Respondents who tested positive for the HD mutation were concerned about discrimination in the employment setting, and worried about discrimination in the past year, to a larger extent than other respondents. Tested respondents reported concerns for family members in the family and social settings to a larger extent than non-tested respondents (Table II). Level of Concern and Distress 63 27 24 20 40 60 80 100 % of respondents FIG. 1. Concern for self only, family only, or both (self AND family), by setting and overall (n ¼ 233). *The prevalence of concern for self (only) was signiﬁcantly greater than concern for family (only). †The prevalence of concern for family (only) was signiﬁcantly greater than concern for self (only). (Statistically signiﬁcant differences between self (only) versus family (only) were assessed with McNemar’s test (P < 0.05)). [Color ﬁgure can be seen in the online version of this article, available at http://wileyonlinelibrary.com/journal/ajmgb] Respondents with a self-rated level of concern or distress of 4 or higher were categorized as having high levels of distress. Among the concerned respondents who rated their level of concern, 24.9% (n ¼ 42/169) had high concern for self, and 34.1% (n ¼ 58/170) reported high concern for family. The level of concern was not signiﬁcantly associated with genetic test status, either for self (P ¼ 0.088) or family (P ¼ 0.642). Of the concerned respondents who rated their level of distress, 21.2% (n ¼ 36/170) had high levels of distress for self, and 32.0% (n ¼ 54/169) reported high distress due to concern about genetic discrimination toward their family members. Distress for self was rated higher by mutation-positive respondents than mutation-negative respondents or those who were not tested [n ¼ 20 (30.8%) vs. n ¼ 6 (13.0%) vs. n ¼ 10 BOMBARD ET AL. 221 TABLE II. Concern About Genetic Discrimination by Genetic Test Status (n ¼ 233) Concern by setting (lifetime) Insurance Self Family Family Self Family Social Self Family Employment Self Family Health care Self Family Public sector Self Family Overall concern Concern about GD (lifetime) Self Family Concern about GD (past year) Self Family TOTAL Total sample (n ¼ 233) n (%)a Not tested (n ¼ 66) n (%)a Mutation-negative (n ¼ 84) n (%)a Mutation-positive (n ¼ 83) n (%)a P-valueb 145 (62.2) 127 (54.5) 41 (62.1) 33 (50.0) 48 (57.1) 44 (52.4) 56 (67.5) 50 (60.2) 0.277 0.408 102 (43.8) 110 (47.2) 23 (34.9) 20 (30.3) 42 (50.0) 45 (53.6) 37 (44.6) 45 (54.2) 0.175 0.005 105 (45.1) 124 (53.2) 24 (36.4) 28 (42.4) 42 (50.0) 54 (64.3) 39 (47.0) 42 (50.6) 0.227 0.024 88 (37.8) 97 (41.6) 19 (28.8) 21 (31.8) 25 (29.8) 37 (44.0) 44 (53.0) 39 (47.0) 0.002 0.150 67 (28.8) 67 (28.8) 17 (25.8) 16 (24.2) 19 (22.6) 22 (26.2) 31 (37.4) 29 (34.9) 0.090 0.290 52 (22.3) 67 (28.8) 10 (15.2) 16 (24.2) 17 (20.2) 25 (29.8) 25 (30.1) 26 (31.3) 0.079 0.617 175 (75.1) 171 (73.4) 50 (75.8) 44 (66.7) 60 (71.4) 62 (73.8) 65 (78.3) 65 (78.3) 0.583 0.277 75 (32.2) 120 (51.5) 233 (100.0) 15 (22.7) 29 (43.9) 66 (100.0) 21 (25.0) 49 (58.3) 84 (100.0) 39 (47.0) 42 (50.6) 83 (100.0) 0.001 0.211 a Percentages are calculated by genetic test status. Pearson’s chi-square. Bold font indicates statistical signiﬁcance (P < 0.05). b (16.9%), respectively; P ¼ 0.049]. Importantly, 83.3% of respondents who reported high levels of self-rated distress due to their concern also reported that they had experienced discrimination. Self-rated distress for family was not signiﬁcantly associated with the respondents’ genetic status (P ¼ 0.446). Concerns and Experiences of Discrimination Of the 175 respondents who reported concern in any setting, 49.7% (87/175) also reported experiences of genetic discrimination, which included 40.0% of those who were not tested (20/50), 45.0% of the mutation-negative group (27/60), and 61.5% of the mutationpositive group (40/65). Only 3% of the total sample reported experiencing discrimination without having also reported concern about discrimination (6/233). they had completed university or teachers’ college (OR ¼ 2.64: 95% CI: 1.26–5.54; P ¼ 0.010), were younger than age 25 when they learned of their family history (OR ¼ 4.01; 95% CI: 1.87–8.61; P < 0.001) or were mutation-positive for HD (OR ¼ 3.13; 95% CI: 1.30–7.53; P ¼ 0.011) in the model that combined all settings (Table III). Stratiﬁed by setting, learning about a family history at a younger age was associated with having ‘‘concerns and experiences’’ of discrimination in the insurance settings (OR ¼ 4.26; 95% CI: 1.87–9.69; P ¼ 0.001) or the family/social setting (OR ¼ 4.12; 95% CI: 1.47–11.59; P ¼ 0.007). Mutationpositive status was associated with having ‘‘concerns and experiences’’ of discrimination in the family/social setting (OR ¼ 7.47; 95% CI: 2.53–22.07; P < 0.001). None of the variables attained statistical signiﬁcance in the model of ‘‘Other settings,’’ which combined the employment, health care, and public sector settings. Factors Associated With Experiences of Discrimination Among Concerned Respondents Strategies Used to avoid Discrimination Overall, respondents were more likely to report both ‘‘concern and experiences’’ of genetic discrimination versus ‘‘concern only’’ if Approximately half of respondents employed the following strategies to mitigate discrimination based on their family history: 0.469 0.111 0.26–3.43 0.58–4.83 0.95 1.67 118 0.718 <0.001 0.37–4.28 2.53–22.07 1.25 7.47 Respondents could report concerns and/or experiences in more than one setting. P-values < 0.05 are highlighted in bold font. a ‘‘Other settings’’ include employment, health care and government. b Reference category. 0.26–1.86 0.84–5.34 0.70 2.12 145 0.974 0.011 0.99 3.13 175 0.40–2.40 1.30–7.53 0.58–3.65 1.45 109 0.007 1.47–11.59 4.12 0.939 0.341 133 0.001 1.87–9.69 136 4.01 163 1.87–8.61 <0.001 4.26 0.27–1.74 0.69 115 0.171 0.76–4.67 1.89 0.426 126 0.233 0.73–3.54 142 2.64 170 1.26–5.54 0.010 1.61 0.58–4.45 1.61 118 0.504 0.53–3.65 1.39 0.85–5.00 2.07 145 0.050 1.00–5.11 2.26 95% CI OR n P-value 95% CI OR 95% CI n OR Family/social settings (n ¼ 133) P-value 95% CI OR n 174 Marital status Married Not marriedb Highest level of education Completed university/teachers college Have not completed university/teachers collegeb Age when learned of family history of HD Less than age 25 25 years old or olderb Genetic test status Have not been tested for HD Mutation-positive Mutation-negativeb Other settingsa (n ¼ 118) Insurance setting (n ¼ 145) Any setting (n ¼ 175) TABLE III. Factors Associated With ‘‘Concerns and Experiences’’ of Genetic Discrimination (vs. ‘‘Concern Only’’) 0.428 128 0.107 DISCUSSION 0.360 132 educating the public about HD (57.8%; n ¼ 130/225), ‘‘trying to take action to avoid’’ discrimination (54.4%; n ¼ 118/217), and keeping quiet about their family history (50.9%; n ¼ 115/226). Very similar proportions employed such strategies for discrimination due to their genetic test result. Concern about discrimination was signiﬁcantly associated with taking action to avoid discrimination and with keeping quiet about one’s genetic risk. High levels of distress due to concern about discrimination were associated with keeping quiet about one’s family history and taking action to avoid discrimination due to one’s genetic test result (Table IV). In the insurance setting, concern about discrimination was associated with the following strategies in up to one-third of respondents: avoiding applying for insurance, giving up before applying for insurance, and thinking about concealing HD status from an insurance company. Ten percent or less of respondents reported that they kept information out of their medical ﬁle or from relatives due their family history or genetic test result. Experiences of insurance discrimination were associated with avoiding applying for insurance and giving up before applying due to one’s family history (Table V). P-value n AMERICAN JOURNAL OF MEDICAL GENETICS PART B P-value 222 Concern for genetic discrimination was frequent in our sample: 86% of respondents reported concerns for themselves or their relatives, largely in the insurance, family, and social settings. Concerns were not necessarily accompanied by experiences of discrimination: approximately 50% of the concerned individuals reported that they experienced discrimination. Overall, concerned respondents who completed university or teachers’ college, who learned about their family history of HD at a younger age, and who were mutation-positive for HD were more likely to experience discrimination than others who were concerned. Concerns for discrimination were rarely attributed to genetic test results alone but prompted respondents to employ a range of strategies to mitigate discrimination. Importantly, some respondents reported high levels of self-rated distress due to concern about discrimination towards family (32%) or themselves (21%). It is notable that the prevalence of overall concern for oneself is almost twice as high as the prevalence of self-reported experiences of discrimination within this sample (75.1% (175/233) vs. 39.9% (93/233) [Bombard et al., 2009]). These ﬁndings are consistent with other research that suggests that concerns for discrimination exceed reported experiences [Wingrove et al., 1996; Peterson et al., 2002; Armstrong et al., 2003; Apse et al., 2004; Erwin et al., 2010]. Generally, the settings in which concern is most prevalent in this sample reﬂects settings in which experiences of discrimination are most frequent [Bombard et al., 2009]: in insurance, family and social settings, and to a lesser extent in employment, public and health care settings. It is also important to highlight that the family and social settings emerged as important sources of concern for oneself and one’s relatives and of experiences of discrimination (particularly when making reproductive choices and establishing relationships). The prevalence of these concerns and experiences in interpersonal contexts (i.e., family and social settings) underscore the inter- and intra-generational impacts of genetic disorders. 0.094 0.111 0.034 0.399 0.002 0.003 0.016 0.595 n (%) 74 45 (48.9) 29 (44.6) 73 43 (57.3) 30 (38.0) 73 46 (58.2) 27 (34.6) 74 46 (59.7) 28 (35.0) P-value n (%) 19 13 (29.5) 6 (20.5) 19 15 (35.7) 4 (13.3) 19 15 (32.6) 4 (15.9) 19 15 (32.6) 4 (14.9) P-value 223 Respondents could report more than one strategy. Bold font indicates statistical signiﬁcance. a Results did not signiﬁcantly vary if respondents had experiences of discrimination or not. b Denominator based on number who had concern, excluding missing cases who did not provide information about their level of distress. — — — — — — — 0.047 <0.001 — 0.020 0.109 0.083 0.090 n (%) 167 102 (78.5) 65 (68.4) 162 100 (84.7) 62 (62.6) 168 92 (80.0) 76 (68.5) Talk to others about HD in order to educate the public Used this strategy Did not use this strategy Try to take action to avoid the possible situation Used this strategy Did not use this strategy Keep quiet about your family history of HD Used this strategy Did not use this strategy Keep quiet about your genetic test result Used this strategy Did not use this strategy Total (n) 225 130 95 217 118 99 226 115 111 P-value n (%) 28 13 (13.0) 15 (23.4) 28 21 (21.4) 7 (11.5) 28 21 (23.1) 7 (9.5) P-value Total (n) 157 92 65 154 75 79 157 79 78 157 77 80 Had concerna Had distressb Had concerna Related to family history TABLE IV. Strategies Used to Avoid Genetic Discrimination (n ¼ 233) Related to genetic test result Had distressb BOMBARD ET AL. Thus, in addition to focusing on protections from institutional discrimination (such as insurance and employment), it would be useful to develop educational or clinical interventions to address the ways in which genetic information may inﬂuence interpersonal relationships. The need for educational or clinical interventions may be further reinforced by the association between concern about discrimination and high levels of distress. Not only was concern about discrimination highly distressing for some respondents, but a high proportion of respondents who reported high levels of selfrated distress due to their concern also reported that they had experienced discrimination (83.3%). Although psychological distress is a recognized consequence of genetic testing [Broadstock et al., 2000; Almqvist et al., 2003; Decruyenaere et al., 2003; Hayden and Bombard, 2005] and high levels of self-rated distress have been associated with experiences of discrimination [Bombard et al., 2009], distress has not previously been linked to concerns for discrimination. Our ﬁndings suggest that there is a compounding effect between concern and experiences of discrimination that results in high levels of self-rated distress in some people. Further, the strategies related to keeping quiet about the family history and taking action to mitigate discrimination based on genetic test results were signiﬁcantly associated with high self-rated distress. Notably, 75% of those who reported high levels of distress also reported low satisfaction with the strategies used to prevent anticipated discrimination, compared to 50% of those who did not report high levels of distress (P < 0.017, post-hoc analysis). This relationship between distress and satisfaction was based on concern related to their family history, and did not vary signiﬁcantly by genetic test results. This points to the importance of the family history as a prominent factor in the concerns and distress about discrimination, and leads to speculation about the effectiveness of family coping strategies and family dynamics. These ﬁndings echo previous calls for interventions to cope with fears of discrimination, particularly interventions aimed at increasing individuals’ self-efﬁcacy and reduce distress [Chen et al., 2009; Olabi, 2009; Thornicroft et al., 2009]. We found that concerns were rarely attributed to genetic test results alone but were attributed to both family history and genetic test results, or to family history alone. Family history was reported as underlying most discrimination experiences by this sample [Bombard et al., 2009]. These results underscore the importance of the family history in discrimination. While discrimination may be more likely among those who receive mutation-positive results, all asymptomatic individuals are at risk for discrimination because of their family history. Ultimately, having a family history of HD makes individuals vulnerable to the risk of genetic discrimination. Recognition of this fact may help to allay patients’ concerns about pursing genetic testing and potentially increase their engagement with clinical care, especially since stigma and the fear of discrimination are thought to have resulted in inaccurate estimates of the true prevalence of HD, adversely affecting research and clinical supports for HD families [Anonymous, 2010; Rawlins, 2010]. Finally, we identiﬁed factors that distinguished individuals who reported both concerns and experiences of discrimination from those who only reported concerns. Those who completed university or teachers’ college, who learned about their family history of HD at Bold font indicates statistical signiﬁcance. a Had concern about genetic discrimination in the insurance setting. b Denominator is number of individuals reporting concern. c Pearson’s chi-square test, unless otherwise noted. d Fisher’s exact test. Have avoided applying due to fear of disclosing status Used this strategy Did not use this strategy Have ever ‘‘given up’’ before applying Used this strategy Did not use this strategy Have thought about concealing status from insurance company Used this strategy Did not use this strategy Have kept information out of medical ﬁle Used this strategy Did not use this strategy Have concealed status from relatives due to insurance concerns for others Used this strategy Did not use this strategy Total (n) 222 64 158 221 58 163 226 73 153 225 22 203 226 12 214 9 (75.0) 129 (60.3) n (%) 137 55 (85.9) 82 (51.9) 136 (61.5) 49 (84.5) 87 (53.4) 139 58 (79.5) 81 (52.9) 138 18 (81.8) 120 (59.1) 0.376d 0.038 <0.001 <0.001 <0.001 P-valuec n (%) 58 29 (52.7) 29 (35.4) 58 30 (61.2) 28 (32.2) 58 28 (48.3) 30 (37.0) 58 11 (61.1) 47 (39.2) 58 4 (44.4) 54 (41.9) 1.000d 0.079 0.185 0.001 0.044 P-valuec Total (n) 151 37 114 150 33 117 157 42 115 157 16 141 159 11 148 5 (45.5) 53 (35.8) n (%) 56 28 (75.7) 28 (24.6) 55 26 (78.8) 29 (24.8) 57 27 (64.3) 30 (26.1) 58 11 (68.8) 47 (33.3) 0.531d 0.005 <0.001 <0.001 <0.001 P-valuec n (%) 28 15 (53.6) 13 (46.4) 28 15 (57.7) 13 (44.8) 28 15 (55.6) 13 (43.3) 29 7 (63.6) 22 (46.8) 29 2 (40.0) 27 (50.9) 1.000d 0.315 0.357 0.341 0.593 P-valuec Had experienceb Had concerna Had concerna Had experienceb Related to genetic test result Related to family history TABLE V. Strategies Used by Respondents to Avoid Insurance Discrimination (n ¼ 233) 224 AMERICAN JOURNAL OF MEDICAL GENETICS PART B BOMBARD ET AL. a younger age, and who were mutation-positive for HD were more likely to report discrimination experiences than others who were concerned. While we are not aware of other studies that explore predictors of concern and experiences of discrimination, a few empirical studies have explored predictors of concern for genetic discrimination [Lehmann et al., 2002; Hall et al., 2005]. Despite the wide-range of factors explored, education has consistently emerged as a signiﬁcant predictor of concern for discrimination. Some studies have found that higher levels of education were associated with concern for discrimination [Lehmann et al., 2002; Baruch and Hudson, 2008], while another found a nonlinear relationship [Hall et al., 2005]. Our study suggests that higher education (i.e., university completion) is associated with experiences of discrimination among those who have had concern for discrimination. There are several caveats in the interpretation of our ﬁndings. Participants may reﬂect a highly educated and self-selected group who may be emotionally robust and may have been better able to recognize and articulate their experiences of discrimination than those with less education or those in advanced stages of HD. Further, we do not know at what point respondents became concerned about particular situations, how long they had been concerned, if they were concerned at the time of the study or because of participating in the study, or the temporal relationships between concerns and experiences or strategies and distress. Further, our distress scale was not intended for clinical assessment and levels of distress may vary over time. Attributions to family history or genetic test results were based on patients’ reports and were not veriﬁed. We also relied on self-reported experiences of discrimination rather than conﬁrmed episodes. However, cases of consumer-reported experiences of genetic discrimination have been veriﬁed by others [Barlow-Stewart et al., 2009]. The small sample sizes for some settings may have affected the precision of our estimates and our ability to detect statistically signiﬁcant relationships. Finally, this study may not be generalizable to jurisdictions without socialized health care systems or to other disease populations. Comparative and cross-cultural studies on discrimination in other neurodegenerative, hereditary cancer, and cardiogenetic populations in different jurisdictions are thus warranted. Despite these limitations, our study addresses several gaps identiﬁed in previous stigma and discrimination research, including the impact of family history, education, age at which one learned of the family history, and urban/rural status [Chen et al., 2009; Olabi, 2009]. Moreover, the sample included only symptom-free individuals, so the impact of genetic risk (rather than symptom presentation) could be assessed. Concern for discrimination is nearly universal among individuals at risk of HD, and has effects on behavioral patterns and selfrated distress. Our ﬁndings illuminate the nature of these concerns and characterize concerned individuals whose worries are coupled with experiences of discrimination. These results may also be used to develop tools to mitigate the threat of discrimination and its effects. 225 Canadian Institutes of Health Research (CIHR) was awarded to Michael Hayden and Joan Bottorff. Yvonne Bombard was supported by doctoral awards from the CIHR and the Michael Smith Foundation for Health Research/Child and Family Research Institute during the conduct of this work; by postdoctoral fellowships from the CIHR, and CIHR Strategic Training Fellowships of ‘‘Public Health Policy’’ and ‘‘Health Care, Technology and Place’’ during the writing of this manuscript; and, is currently funded by a postdoctoral fellowship from the CIHR. 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