Genetic counseling among minority populations in the era of precision medicine.

Precision medicine includes the use of genetic variation to determine the prevention, pathology, management, and treatment of disease, which has the potential to significantly change the practice of healthcare. As such, its success depends on (a) having reliable information about the effects of genetic variation on disease processes; and (b) the patient's understanding of their own genetic makeup such that they can use that information to affect their lifestyle and diet. Given the history of low engagement of under-represented minority populations in both clinical genetic services and genetic research, both of these aspects will be challenged and must be addressed before the benefits of precision medicine will be fully realized. Reflecting on lessons learned in the field of cancer genetic counseling, we present key issues to consider as we look forward to providing genetic counseling to minority communities in the context of precision medicine.

Heritability of serum iron measures in the hemochromatosis and iron overload screening (HEIRS) family study.

Heritability is the proportion of observed variation in a trait among individuals in a population that is attributable to hereditary factors. The Hemochromatosis and Iron Overload Screening family study estimated heritability of serum iron measures. Probands were HFE C282Y homozygotes or non-C282Y homozygotes with elevated transferrin saturation (TS > 50%, men; TS > 45%, women) and serum ferritin concentration (SF > 300 microg/L, men; SF > 200 microg/L, women). Heritability (h(2)) was estimated by variance component analysis of TS, natural logarithm (ln) of SF, and unsaturated iron-binding capacity (UIBC). Participants (N = 942) were 77% Caucasians, 10% Asians, 8% Hispanics, and 5% other race/ethnicities. Average age (SD) was 49 (16) years; 57% were female. For HFE C282Y homozygote probands and their family members, excluding variation due to HFE C282Y and H63D genotype and measured demographic and environmental factors, the residual h(2) (SE) was 0.21 (0.07) for TS, 0.37 (0.08) for ln SF, and 0.34 (0.08) for UIBC (all P < 0.0004 for comparisons with zero). For the non-C282Y homozygote proband group, residual h(2) was significant with a value of 0.64 (0.26) for ln SF (P = 0.0096). In conclusion, serum iron measures have significant heritability components, after excluding known genetic and nongenetic sources of variation.

Accuracy of family history of hemochromatosis or iron overload: the hemochromatosis and iron overload screening study.

BACKGROUND & AIMS: The aim of this study was to assess the analytic validity of self-reported family history of hemochromatosis or iron overload. METHODS: A total of 141 probands, 549 family members, and 641 controls participated in the primary care Hemochromatosis and Iron Overload Screening Study. Participants received a postscreening clinical examination and completed questionnaires about personal and family histories of hemochromatosis or iron overload, arthritis, diabetes, liver disease, and heart disease. We evaluated sensitivities and specificities of proband-reported family history, and concordance of HFE genotype C282Y/C282Y in probands and siblings who reported having hemochromatosis or iron overload. RESULTS: The sensitivities of proband-reported family history ranged from 81.4% for hemochromatosis or iron overload to 18.4% for liver disease; specificities for diabetes, liver disease, and heart disease were greater than 94%. Hemochromatosis or iron overload was associated with a positive family history across all racial/ethnic groups in the study (odds ratio, 14.53; 95% confidence intervals, 7.41-28.49; P < .0001) and among Caucasians (odds ratio, 16.98; 95% confidence intervals, 7.53-38.32; P < .0001). There was 100% concordance of HFE genotype C282Y/C282Y in 6 probands and 8 of their siblings who reported having hemochromatosis or iron overload. CONCLUSIONS: Self-reported family history of hemochromatosis or iron overload can be used to identify individuals whose risk of hemochromatosis or iron overload and associated conditions is increased. These individuals could benefit from further evaluation with iron phenotyping and HFE mutation analysis.

Screening for hemochromatosis and iron overload: satisfaction with results notification and understanding of mailed results in unaffected participants of the HEIRS study.

AIM: The purpose of this study was to assess the level of satisfaction and understanding of test results, by a sample of non-C282Y homozygous participants in the hemochromatosis and iron overload screening (HEIRS) study, who received serum ferritin (SF), transferrin saturation (TS), and HFE gene test results by mail. METHODS: Approximately 1 month after receiving test results by mail, participants were surveyed about understanding of and satisfaction with results notification. RESULTS: Overall, participants were satisfied with receiving test results by mail. Participants receiving results with one or two HFE mutations or TS and/or SF levels outside the normal range (an "alert value") were less likely to be satisfied with this method of notification. Participants with normal HFE test results understood their results and recommendations better than those with one or two mutations. Although all participants received results letters in their native language, English-speaking participants had higher mean understanding scores than Mandarin, Vietnamese, or Spanish-speaking participants. CONCLUSION: Participants were satisfied with receiving test results by mail. However, the level of understanding of the results was not sufficient for this mode of results notification to stand alone, especially for non-English speaking participants, and all participants with one or more test results outside the normal range.

Results communication and patient education after screening for possible hemochromatosis and iron overload: experience from the HEIRS Study of a large ethnically and linguistically diverse group.

PURPOSE: We assessed the effectiveness of educational interventions for conveying clinical findings and information about hereditary hemochromatosis (HH) and iron overload (IO) to individuals evaluated clinically after initial screening for HH/IO with serum ferritin (SF) concentration, transferrin saturation (TS), and HFE genotyping. METHODS: A questionnaire mailed to 2300 cases and controls 1 month after a letter summarizing clinical findings measured understanding of results and recommendations, knowledge of HH/IO, and satisfaction with information received. RESULTS: Of 1622 (70.5%) participants completing relevant items, 83.6% were satisfied with receiving initial screening results by mail, 93.4% found information clear and easy to understand, 89.2% generally felt they got enough information, but 47.5% still had questions. C282Y/C282Y homozygosity with normal TS/SF predicted the best understanding of genetic results. Many with no mutations thought relatives were at risk. Iron levels created most confusion, and a third incorrectly recalled treatment recommendations. Having any abnormal result, lower education, older age, and being non-white, and/or non-English speaking predicted lower understanding. CONCLUSIONS: Combining genotypic and phenotypic screening for HH/IO creates additional difficulties in communicating results-particularly to those with low health literacy. Explaining aberrant iron TS and SF levels and low-risk genotypes, follow-up recommendations, and risk to relatives will need creative, culturally appropriate strategies.

Concerns in a primary care population about genetic discrimination by insurers.

PURPOSE: Fear of genetic discrimination might deter participation in research or therapy. This is a major impetus for laws limiting insurers' use of genetic information, yet there is little information about the extent of this fear in the general population and how it varies by social factors. METHODS: This study measures concern about insurance problems relating to genetic testing, as part of primary-care screening for hereditary hemochromatosis (iron overload). Data come from a multiethnic, primary care-based survey of 86,859 adults in five field centers in the United States (AL, CA, DC, HI, OR), and one in Canada (Ontario). Logistic regression was used to model the probability of agreeing to the question "Genetic testing is not a good idea because you might have trouble getting or keeping your insurance." RESULTS: Overall, 40.0% of participants agreed. Adjusting for other characteristics, African Americans and Asians were much less likely (OR = 0.52 and 0.39), and Hispanics were more likely (OR = 1.124), than Caucasians to express concern about insurance discrimination. Participants under 65 years old, US residents, and those without a high school diploma were substantially more likely to be concerned (ORs ranging from 1.4-1.6), as were participants with lower mental health scores. Education showed a nonlinear relationship, with significantly higher concern among both those with less than a high school education and those with a college degree, compared to high school graduates. CONCLUSIONS: Concern about genetic discrimination varies substantially by race and other demographic factors and by nationality. One possible explanation for lower concern about Canadians and by people over 64 is that both groups are covered by social insurance for health care (Medicare). However, US residents in states with some legal protections against genetic discrimination had more, not less, concern than either Canadians or US residents in states with no legal protections.