Cancer Genetic Counselor Information Needs for Risk Communication: A Qualitative Evaluation of Interview Transcripts

Personalized medicine is a model of healthcare that is predictive, personalized, preventive and participatory (“P4 Medicine”). Genetic counselors are an ideal group to study when designing tools to support cancer P4 Medicine activities more broadly. The goal for this work was to gain a better understanding of the information cancer genetic counselors seek from their patients to facilitate effective information exchange for discussing risk. This was an analysis of a qualitative data set from interviews of eight cancer genetic counselors, recruited from three institutions. Genetic counselors at each site were interviewed using a semi-structured, open-ended questionnaire. A selective coding approach was used to determine major themes associated with genetic counseling information needs for communicating risk. We generated a model for understanding categories of genetic counseling information needs to support risk communication activities. Common activities for risk communication included risk assessment and tailoring communication. Categories of information needs included: (a) clinical patient characteristics, (b) social and cognitive patient characteristics and (c) patient motivation and goals for the genetic counseling session. A logical next step is for this model to inform the design of software systems for pre-visit patient planning and delivering just-in-time educational information to facilitate cancer risk communication activities

Advances in the Understanding of the Genetic Determinants of Congenital Heart Disease and Their Impact on Clinical Outcomes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143784/1/jah33022.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143784/2/jah33022_am.pd

Anticipating issues related to increasing preimplantation genetic diagnosis use: a research agenda

Increasing use of preimplantation genetic diagnosis (PGD) poses numerous clinical, social, psychological, ethical, legal and policy dilemmas, many of which have received little attention. Patients and providers are now considering and using PGD for a widening array of genetic disorders, and patients may increasingly seek ‘designer babies.’ In the USA, although governmental oversight policies have been discussed, few specific guidelines exist. Hence, increasingly, patients and providers will face challenging ethical and policy questions of when and for whom to use PGD, and how it should be financed. These issues should be better clarified and addressed through collection of data concerning the current use of PGD in the USA, including factors involved in decision making about PGD use, as well as the education of the various communities that are, and should be, involved in its implementation. Improved understanding of these issues will ultimately enhance the development and implementation of future clinical guidelines and policies

Decision‐Making About Reproductive Choices Among Individuals At‐Risk for Huntington's Disease

We explored how individuals at‐risk for HD who have or have not been tested make reproductive decisions and what factors are involved. We interviewed 21 individuals (8 with and 4 without the mutation, and 9 un‐tested) in‐depth for 2 hours each. At‐risk individuals faced a difficult series of dilemmas of whether to: get pregnant and deliver, have fetal testing, have pre‐implantation genetic diagnosis, adopt, or have no children. These individuals weighed competing desires and concerns: their own desires vs. those of spouses vs. broader moral concerns (e.g., to end the disease; and/or follow dictates against abortion) vs. perceptions of the interests of current or future offspring. Quandaries arose of how much and to whom to feel responsible. Some changed their perspectives over time (e.g., first “gambling,” then being more cautious). These data have critical implications for genetic counselors and other health care workers and future research, particularly as more genetic tests become available

Disclosures of Huntington disease risk within families: Patterns of decision‐making and implications

Patterns of disclosure of Huntington disease risk and genetic test results among family members are important, but have been underexplored. We interviewed 21 individuals in‐depth—eight mutation‐positive for HD, four mutation‐negative, and nine not tested—for 2 hr each. Within families, critical questions arose of what, when, and to whom to disclose, and what to do post‐disclosure. Interviewees wrestled with dilemmas of what to tell (e.g., suspicions vs. confirmed symptoms; initiation vs. completion of testing; partial vs. indirect information), how to disclose (e.g., planning in advance vs. “blurting out” information in arguments), and whether and how to tell extended family members. Questions arose of when to tell (i.e., to avoid disclosing “too early” or “too late”). Similarities and differences emerged related to types of relationships (e.g., parents telling offspring vs. offspring telling parents vs. siblings telling each other). Individuals often disclosed because of perceived duty to foster the health of their family members, enabling these others to pursue appropriate medical evaluation, if desired. Yet tensions arose because the information could burden these members, who also have rights to remain “in denial” if they wish and not discuss the topic or pursue testing. Post‐disclosure, dilemmas emerged of whether and how much to encourage family members to pursue testing. These data shed important light on critical issues that have received little, if any, attention concerning what, how, and when disclosure occurs, and have key implications for at‐risk individuals, genetic counselors, and other health care workers (HCWs), and for future research. At‐risk individuals would benefit from considering these issues in advance. HCWs need to realize that these decisions are multi‐faceted. Future research can explore whether, when, how, and how often HCWs raise these issues with individuals

The Impact of Heterozygous KCNK3 Mutations Associated With Pulmonary Arterial Hypertension on Channel Function and Pharmacological Recovery

Background-Heterozygous loss of function mutations in the KCNK3 gene cause hereditary pulmonary arterial hypertension (PAH). KCNK3 encodes an acid-sensitive potassium channel, which contributes to the resting potential of human pulmonary artery smooth muscle cells. KCNK3 is widely expressed in the body, and dimerizes with other KCNK3 subunits, or the closely related, acid-sensitive KCNK9 channel. Methods and Results-We engineered homomeric and heterodimeric mutant and nonmutant KCNK3 channels associated with PAH. Using whole-cell patch-clamp electrophysiology in human pulmonary artery smooth muscle and COS7 cell lines, we determined that homomeric and heterodimeric mutant channels in heterozygous KCNK3 conditions lead to mutation-specific severity of channel dysfunction. Both wildtype and mutant KCNK3 channels were activated by ONO-RS-082 (10 mu mol/L), causing cell hyperpolarization. We observed robust gene expression of KCNK3 in healthy and familial PAH patient lungs, but no quantifiable expression of KCNK9, and demonstrated in functional studies that KCNK9 minimizes the impact of select KCNK3 mutations when the 2 channel subunits co-assemble. Conclusions-Heterozygous KCNK3 mutations in PAH lead to variable loss of channel function via distinct mechanisms. Homomeric and heterodimeric mutant KCNK3 channels represent novel therapeutic substrates in PAH. Pharmacological and pH-dependent activation of wildtype and mutant KCNK3 channels in pulmonary artery smooth muscle cells leads to membrane hyperpolarization. Co-assembly of KCNK3 with KCNK9 subunits may provide protection against KCNK3 loss of function in tissues where both KCNK9 and KCNK3 are expressed, contributing to the lung-specific phenotype observed clinically in patients with PAH because of KCNK3 mutations.National Heart, Lung, and Blood Institute (NHLBI)Cardiovascular Medical Research and Education Fund (CMREF)Columbia Univ, Coll Phys & Surg, Dept Pharmacol, New York, NY USAColumbia Univ, Dept Pediat, Coll Phys & Surg, New York, NY 10027 USAUniv Fed São Paulo, Paulista Sch Med, Dept Biophys, São Paulo, BrazilNew York Stem Cell Fdn, Res Inst, New York, NY USAUniv Fed São Paulo, Paulista Sch Med, Dept Biophys, São Paulo, BrazilNHLBI: F30 HL129656NHLBI R24 grant: R24HL123767Web of Scienc

CANOES: detecting rare copy number variants from whole exome sequencing data

We present CANOES, an algorithm for the detection of rare copy number variants from exome sequencing data. CANOES models read counts using a negative binomial distribution and estimates variance of the read counts using a regression-based approach based on selected reference samples in a given dataset. We test CANOES on a family-based exome sequencing dataset, and show that its sensitivity and specificity is comparable to that of XHMM. Moreover, the method is complementary to Gaussian approximation-based methods (e.g. XHMM or CoNIFER). When CANOES is used in combination with these methods, it will be possible to produce high accuracy calls, as demonstrated by a much reduced and more realistic de novo rate in results from trio data

Association of Allelic Variation in Genes Mediating Aspects of Energy Homeostasis with Weight Gain during Administration of Antipsychotic Drugs (CATIE Study)

Antipsychotic drugs are widely used in treating schizophrenia, bipolar disorder, and other psychiatric disorders. Many of these drugs, despite their therapeutic advantages, substantially increase body weight. We assessed the association of alleles of 31 genes implicated in body weight regulation with weight gain among patients being treated with specific antipsychotic medications in the clinical antipsychotic trials in intervention effectiveness study, we found that rs2237988 in Potassium Channel Inwardly Rectifying Subfamily J Member 11 (KCNJ11), rs13269119 in Solute carrier family 30 member 8 (SLC30A8), and rs9922047 in fat mass and obesity associated (FTO) were associated with percent weight gain. We also observed the significant interaction of rs11643744 by treatment effect on the weight gain