Determining the effects and challenges of incorporating genetic testing into primary care management of hypertensive patients with African ancestry.

People of African ancestry (Blacks) have increased risk of kidney failure due to numerous socioeconomic, environmental, and clinical factors. Two variants in the APOL1 gene are now thought to account for much of the racial disparity associated with hypertensive kidney failure in Blacks. However, this knowledge has not been translated into clinical care to help improve patient outcomes and address disparities. GUARDD is a randomized trial to evaluate the effects and challenges of incorporating genetic risk information into primary care. Hypertensive, non-diabetic, adults with self-reported African ancestry, without kidney dysfunction, are recruited from diverse clinical settings and randomized to undergo APOL1 genetic testing at baseline (intervention) or at one year (waitlist control). Providers are educated about genomics and APOL1. Guided by a genetic counselor, trained staff return APOL1 results to patients and provide low-literacy educational materials. Real-time clinical decision support tools alert clinicians of their patients' APOL1 results and associated risk status at the point of care. Our academic-community-clinical partnership designed a study to generate information about the impact of genetic risk information on patient care (blood pressure and renal surveillance) and on patient and provider knowledge, attitudes, beliefs, and behaviors. GUARDD will help establish the effective implementation of APOL1 risk-informed management of hypertensive patients at high risk of CKD, and will provide a robust framework for future endeavors to implement genomic medicine in diverse clinical practices. It will also add to the important dialog about factors that contribute to and may help eliminate racial disparities in kidney disease.

Genetic and lifestyle causal beliefs about obesity and associated diseases among ethnically diverse patients: a structured interview study.

BACKGROUND: New genetic associations with obesity are rapidly being discovered. People's causal beliefs about obesity may influence their obesity-related behaviors. Little is known about genetic compared to lifestyle causal beliefs regarding obesity, and obesity-related diseases, among minority populations. This study examined genetic and lifestyle causal beliefs about obesity and 3 obesity-related diseases among a low-income, ethnically diverse patient sample. METHODS: Structured interviews were conducted with patients attending an inner-city hospital outpatient clinic. Participants (n=205) were asked how much they agreed that genetics influence the risk of obesity, type 2 diabetes, heart disease, and cancer. Similar questions were asked regarding lifestyle causal beliefs (overeating, eating certain types of food, chemicals in food, not exercising, smoking). In this study, 48% of participants were non-Hispanic Black, 29% Hispanic and 10% non-Hispanic White. RESULTS: Over two-thirds (69%) of participants believed genetics cause obesity 'some' or 'a lot', compared to 82% for type 2 diabetes, 79% for heart disease and 75% for cancer. Participants who held genetic causal beliefs about obesity held more lifestyle causal beliefs in total than those who did not hold genetic causal beliefs about obesity (4.0 vs. 3.7 lifestyle causal beliefs, respectively, possible range 0-5, p=0.025). There were few associations between causal beliefs and sociodemographic characteristics. CONCLUSIONS: Higher beliefs in genetic causation of obesity and related diseases are not automatically associated with decreased lifestyle beliefs. Future research efforts are needed to determine whether public health messages aimed at reducing obesity and its consequences in racially and ethnically diverse urban communities may benefit from incorporating an acknowledgement of the role of genetics in these conditions.

Prenatal genetic screening in the Ashkenazi Jewish population.

The Ashkenazi Jewish community is a unique and ideal population in which to provide multiple disease screening because detection rates are high (> 95%) by testing a limited number of mutations. The residual risk that remains is very low. In addition, the lessons learned from carrier screening in this community indicate that only through genetic counseling and education can screening in the general population gain wide acceptance and provide maximum benefit.

Prenatal genetic carrier testing using triple disease screening.

CONTEXT: Rapid progress in gene discovery has dramatically increased diagnostic capabilities for carrier screening and prenatal testing for genetic diseases. However, simultaneous prenatal carrier screening for prevalent genetic disease has not been evaluated, and patient acceptance and attitudes toward this testing strategy remain undefined. OBJECTIVE: To evaluate an educational, counseling, and carrier testing program for 3 genetic disorders: Tay-Sachs disease (TSD), type 1 Gaucher disease (GD), and cystic fibrosis (CF) that differ in detectability, severity, and availability of therapy. DESIGN: Potential participants received education and genetic counseling, gave informed consent, chose screening tests, and completed pre-education and posteducation questionnaires that assessed knowledge, attitudes toward genetic testing, and disease testing preferences. SETTING: Medical genetics referral center. PATIENTS: Volunteer sample of 2824 Ashkenazi Jewish individuals enrolled as couples who were referred for TSD testing. INTERVENTION: Genetic counseling, education, and if chosen, genetic testing for any or all 3 disorders. MAIN OUTCOME MEASURE: Acceptance of screening for each of the 3 disorders. Secondary outcomes include attitudes toward genetic testing and reproductive considerations. RESULTS: Of the 2824 individuals tested for TSD, 97% and 95% also chose testing for CF and GD, respectively. The frequency of detected carriers was 1:21 for TSD, 1 :25 for CF, and 1:18 for GD. Twenty-one carriercoupleswere identified, counseled, and all postconception couples opted for prenatal diagnosis. Pre-education and posteducation questionnaires revealed that patients initially knew little about the diseases, but acquired disease information and increased knowledge of genetic concepts. Education and genetic counseling increased understanding and retention of genetic concepts and disease-related information, and minimized test-related anxiety. Although individuals sought screening for all 3 diseases, reproductive attitudes and decisions varied directly with disease severity and treatability. CONCLUSIONS: These findings emphasize the importance of genetic counseling for prenatal carrier testing and may improve understanding, acceptance, and informed decision making for prenatal carrier screening for multiple genetic diseases.

Prenatal diagnosis of a familial interchromosomal insertion of Y chromosome heterochromatin.

An apparently unbalanced karyotype containing an abnormal chromosome 11 was identified in a 16-week female fetus by analysis of cultured amniocytes. Fluorescence in situ hybridization (FISH) with a chromosome 11 paint identified the presence of an insertion in band 11q24. Parental karyotyping documented an unbalanced karyotype with the same der(11) chromosome in the phenotypically normal father. CBG-banding and FISH identified the insertion to be Yq12 heterochromatin: 46,XY, der(11)ins(11;Y)(q24;q12q12).ish der(11) (wcp11+,DYZ1+). The same der(11) chromosome was also found in the phenotypically normal paternal grandmother, demonstrating this additional Y chromosomal material did not affect normal female sexual development or fertility. The parents elected to continue the pregnancy and a normal girl was born at term, further confirming that this rare familial variant has no clinical significance. This case illustrates the importance of family studies, appropriate banding, and FISH analyses to accurately characterize apparent chromosomal abnormalities.

Confined placental mosaicism in CVS and pregnancy outcome.

The perinatal outcome of 26 patients with confined placental mosaicism (CPM) detected in chorionic villus sampling (CVS) who wished to continue their pregnancies was compared with that of two controls per patient matched for age and parity (n = 52). There were no significant differences in birth weight or gestational age at delivery between patients with CPM and controls. There were no cases of intrauterine growth retardation (IUGR) in the CPM patients as compared with two (2/52, 3.8 per cent) in the control group (P > 0.05). There was no significant increase in fetal loss between the study group (1/26, 3.6 per cent) and the controls (1/52, 1.9 per cent) (P > 0.05).