Utility Of Genetic Information Research Articles

Assessing Stakeholder Perceptions of the Utility of Genetic Information for the Clinical Care of Mental Health Disorders: We Have a Will but Need to See the Way.

Academic stakeholders' (primarily mental health researchers and clinicians) practices and attitudes related to the translation of genetic information into mental health care were assessed. A three-part survey was administered at two large, urban universities. Response frequencies were calculated. Participants (N = 64) reported moderate levels of translational practice, adequate levels of genetic knowledge, and variable levels of genetic competence. They held positive attitudes toward translating genetic information about mental health broadly but negative attitudes about the impact that such information would have on specific aspects of care. The current study lays the groundwork for further inquiry into translating genetic information to mental health care.

Exploring African American males' attitudes towards genetic testing for prostate cancer risk.

e13552 Background: African American (AA) males have disproportionately high prostate cancer (PCA) incidence and mortality rates compared to men of other races. While genetic testing for PCA is rapidly expanding, AA men represent fewer than 10% of those who undergo genetic counseling and testing. Barriers for AA males may include a lack of awareness or understanding, cultural beliefs, financial and access-to-care limitations, fear of discrimination, and mistrust in the healthcare system. These issues may be exacerbated among low-income, urban AA males. Methods: We conducted two focus groups with AA males who live in a low-resource neighborhood in a major US city to explore their understanding about PCA, challenges in obtaining and discussing family health history, and attitudes towards genetic counseling and testing. Prior to the start of the focus groups, men provided informed consent and completed a brief survey to capture demographic and health history information. Focus groups were moderated by a male member of the community, were audio and video recorded, and transcribed verbatim. Transcripts were analyzed using NVivo 12 to deduce themes within the discussions. Results: Seventeen men participated in one of two focus groups. The mean age was 54 years old (range: 40-66). Only 5 men (30%) were married. Ten men (60%) did not report a family history of PCA, while the remaining 7 reported that their father, grandfather, brother or uncle had PCA. All men had a primary care visit in the past 3 years, but only 13 out of 17 men (76%) reported discussing PCA. Focus group discussions and analyses revealed multiple key themes. Men had limited understanding of the prostate and PCA, with somewhat fatalistic views toward cancer. Family history was recognized as an important risk factor for cancer; talking about family history has become easier and more widely accepted. However, there was mixed reaction to genetic testing: most men were unfamiliar with it but were in favor of learning more, while a few did not see the utility of genetic information. Conclusions: AA men continue to have knowledge deficits about PCA. While there is strong understanding that cancer may be hereditary, there is less awareness about PCA genetic testing. Targeted genetic education and addressing access and cost barriers to genetic testing among AA males is needed to increase uptake of genetic testing and participation in genetic trials.

Abstract 03: LDL-C Genetic Risk Score Predicts Hyperlipidemia and Modifies Lipid Trajectory Over the Life Course: The Bogalusa Heart Study

Introduction: Variability in lipid levels is decreased in childhood compared to adulthood. However, few studies have assessed whether genetic information may help to predict hyperlipidemia beyond measured lipid values at this critical developmental stage. Hypothesis: We hypothesized that a low-density lipoprotein cholesterol (LDL-C) genetic risk score (GRS) would predict hyperlipidemia and LDL-C over the life course, even after adjustment for childhood measures. Methods: The analysis included 651 Bogalusa Heart Study participants (63% women, 31% African American, baseline age=9.8 + 3.1 years, median follow-up=40 years) with genome-wide association study (GWAS) data and at least one childhood and one adulthood measure of LDL-C. A weighted LDL-C GRS was constructed using loci from previous GWAS meta-analyses. Hyperlipidemia was defined as an LDL-C > 130 mg/dL or statin use. Cox proportional hazards regression models examined the associations between GRS and hyperlipidemia. Linear and mixed linear regression models were employed to examine the associations of GRS with adulthood LDL-C and life-course LDL-C trajectory, respectively. All models adjusted for age, sex, and childhood LDL-C. Results: Among participants of European ancestry, increasing GRS tertile conferred strong, dose-response increases in the hazards of hyperlipidemia ( Figure ). Similarly, the highest GRS tertile was associated with a 20 mg/dl increased LDL-C level in middle-aged adults compared to the lowest tertile (P<0.0001). Each tertile increase in GRS was also associated with 5.5 mg/dL larger 10-year increase in LDL-C (interaction-P=0.04). No associations were observed among participants of African ancestry. Conclusions: A LDL-C GRS was associated with adulthood LDL-C phenotypes independently of childhood LDL-C values in participants of European but not African ancestry. These findings highlight a need for increased genomics research in diverse populations and suggest a predictive utility of genetic information in childhood.

Patient experience and utility of genetic information: a cross-sectional study among patients tested for cancer susceptibility and thrombophilia

We evaluated whether genetic tests with evidence of clinical and personal utility (i.e. APC and BRCA1/2 tests) are associated with higher satisfaction and a more positive perception of care experience than those with undefined utility (i.e. tests for thrombophilia). A cross-sectional survey was performed through telephone interviews to patients tested for deleterious variants in APC or BRCA1/2 genes, or for inherited thrombophilia (FV Leiden and/or FIIG20210A) during a 5-year period (2008–2012). Three aspects of patient experience were assessed: effective communication through pre- and post-test genetic counselling; collaboration between caregivers on the management of patient care; and impact of genetic testing on quality of life. Overall 237 patients had telephone interviews. Multivariate logistic regression analyses showed that patients tested for APC or BRCA1/2 variants were more likely to be satisfied with both pre- and post-test counselling than those tested for inherited thrombophilia (APC vs. thrombophilia, p = 0.039 and 0.005; BRCA1/2 vs. thrombophilia, p = 0.030 and <0.001). Patients tested for APC were more likely to report an improvement in quality of life than those for thrombophilia (OR = 2.97, 95%CI 1.14, 7.72; p = 0.025). A positive association was observed between patients who underwent BRCA1/2 testing, and self-perceived improvement in quality of life (OR = 1.41, 95%CI 0.74, 2.69; p = 0.294). Tests of undefined clinical and personal utility are associated with a lower degree of patient satisfaction with genetic counselling and no clear opinions on changes in quality of life compared with those with well-defined utility.

Using a Systems-Based Risk Score Approach to Examine Genetic Predisposition to Novelty Seeking

Abstract. Previous research is mixed regarding the relation between dopamine and Novelty Seeking. The goals of the current study were to support the hypotheses that Novelty Seeking is associated with dopamine genes and that modeling genetic risk score increases the utility of genetic information in hypothesis-driven research. The results showed that higher hypodopaminergic genetic risk score positively predicted higher Novelty Seeking score, F(1, 115) = 5.76, p &lt; .01, R2 = 0.06. The findings support study hypotheses and, in combination with previous studies, show the utility of empirically validated system-based risk scores as a means of modeling genetic predisposition in neurobiological systems. This approach provides a mechanism for incorporating genetic predisposition into theory-driven multivariate etiological models of psychological constructs such as personality and mental illness.

Subsets of SNPs define rare genotype classes that predict ischemic heart disease

Single nucleotide polymorphisms (SNPs) are hypothesized to explain the genetic predisposition to ischemic heart disease (IHD) in the general population. Lack of evidence for a role of such variation is fostering pessimism about the utility of genetic information in the practice of medicine. In this study we determined the utility of exonic and 5' SNPs in apolipoprotein E (APOE) and lipoprotein lipase (LPL) when considered singly and in combination for predicting incidence of IHD in 8,456 individuals from the general population during 24 years of follow-up. In men, LPL D9N improved prediction of IHD (P = 0.03) beyond smoking, diabetes and hypertension. The group of men heterozygous and homozygous for the rare D9N variant had a hazard ratio (HR) of 1.69 (95% confidence interval = 1.10-2.58) relative to the most common genotype. Pairwise combinations of D9N with -219G > T in APOE and N291S and S447X in LPL significantly improved the prediction of IHD (P = 0.05 in women, P = 0.04 in men, P = 0.03 in men, respectively) beyond smoking, diabetes and hypertension, and identified subgroups of individuals (n = 6-94) with highly significant HRs of 1.92-4.35. These results were validated in a case-control study (n = 8,806). In conclusion, we present evidence that combinations of SNPs in APOE and LPL identify subgroups of individuals at substantially increased risk of IHD beyond that associated with smoking, diabetes and hypertension.