Managing Health in the Genomic Era: A Guide to Family Health History and Disease Risk

Description

In Managing Health in the Genomic Era: A Guide to Family Health History and Disease Risk, Drs. Vincent C. Henrich, Lori A. Orlando, and Brian H. Shirts discuss the practical considerations surrounding the use of genomic and genetic tests to manage patient health, to provide adult disease risk assessment, to improve diagnosis, and to support effective interventions and treatment. In 10 chapters, evidence-based information and case studies are described and examine the central place of family health history (FHH) in genomic medicine, tools and strategies for compiling and analyzing family health history, how to identify existing and novel genetic markers, how to identify lineage specific (or rare) variants within families, and how to find effective interventions based on genetic testing results and FHH. Factors that influence clinical practice, including gene-environment interactions, FHH social networking, direct to consumer (DTC) genetic testing and data sharing, algorithms for analyzing genetic data, and patient counseling are discussed from the standpoint of clinical practice. Here, frontline healthcare providers will discover succinct commentary and key examples to assist with their local needs. Relevant principles of genetic biology and inheritance are explored and guidance on available support networks and online resources is also provided Copyright Acknowledgments Prologue The growing medical relevance and value of family health history Common chronic diseases shorten productive lifespan for a large proportion of adults Genetic variation does not account for extended productive lifespan, but it can reduce it Family health history is personal and powerful Family health history is a robust predictor of an individual’s disease risk and often indicates the urgent need for evidenc ... Family members share millions of DNA variants and a few increase adult disease onset risk Family health history is a convenient and effective proxy for the effect of genetic variants that increase disease risk Inherited alterations of gene sequence or activity can predispose adult disease onset Familial disease risk is a product of both heredity and shared environment Collection and analysis of useful family health history poses challenges for healthcare The utility of family health history will depend upon new tools and updated models of clinical patient flow Summary and conclusions References Further reading Family health history's place in genomic medicine What is family health history? The value of family health history for informing clinical care What are the levels of risk defined by family health history and what do they mean? Clinical validity and utility of family health history Family health history's relationship to genetic testing Identify the likelihood that a highly penetrant genetic variant is present Mediate the penetrance of a known pathogenic variant Provide evidence to clarify whether a variant of undetermined significance (VUS) is indeed significant or not Guide the search for new genetic drivers of hereditary disease Summary and conclusions References The connection between genetic variation, family health history, and disease risk A genomics primer: What are DNA variants Why do we have SNPs? Most SNP variants have no known medical relevance Some SNPs are associated with disease Summary of SNPs Family health history’s relationship to genetic variants Types of genomic tests currently available What to expect when you get your genetic test result back What to make of direct to consumer (DTC) genetic tests References Family-specific genetic variants: Principles, detection, and clinical interpretation Introduction—The scope and scale human genetic variation Population and family-specific variants can cause high risk and are responsible for most common autosomal recessive disease ... Family-specific variants can cause high risk and are responsible for most autosomal dominant disease What is the expected distribution of family-specific variants in the population and what variants are you likely to see? Classifying rare variants requires application of specific criteria Variants are most often classified on a 5-level scale from pathogenic to benign Family-specific variants are often classified as variants of uncertain significance (VUS) Communicating about variants of uncertain significance in clinical care Understanding evidence behind variants and reclassifying VUS Several different types of evidence are used to understand family-specific variants and classify VUS In-silico data Functional studies Families are among the most efficient ways to ascertain clinical data about rare VUS 52,53 Cosegregation analysis Examples of variant data that can be obtained from families Examples of cosegregation analysis Examples of variant data that can be obtained through family studies beyond cosegregation Conclusion: What to do when with a patient has a genetic variant that you have never seen before Summary and conclusions References Genes and cancer: Implications for FHH analysis The risk for hereditary cancer onset depends on how cell growth regulation is impaired: The BRCA1 / BRCA 2 example Hereditary non-polyposis colorectal cancer (HNPCC, aka Lynch syndrome) also involves variants in genes necessary for DNA re ... A pathogenic variant increases a carrier’s risk for HBOC and Lynch syndrome, but onset requires a second environmentally-in ... Different cancers in a family can arise from the same genetic variant Early age of onset, severity, and recurrence are evidence of a hereditary cancer syndrome Cancer occurrence in second degree relatives may be necessary to diagnose HBOC or Lynch syndromes Diagnosing a hereditary condition in a family sometimes requires simultaneous consideration of several factors Cancer occurrence sometimes involves non-genetic cellular mechanisms Other hereditary cancers result from genetic variants disrupting other cellular mechanisms Pancreatic cancer involves a complex interaction of genetic variation and environment Genetic biomarkers could have utility for refining personal and familial cancer risk assessment Summary and conclusions References Using family health history to identify and reduce modifiable disease risks Cardiovascular disease risk in the population is attributable to the independent contribution of genetic and environmental ... The additive and interactive effects of genetic variants with each other and the environment provide a population measure o ... The relationship between inherited variants and environmental risks depends on a specific condition and may require a speci ... The health effects of controllable environmental factors in individuals and families are not entirely understood Using family health history to assess future health risk Family health history is applied genomics Summary and conclusions References Technology for family health history and collection and analysis Provider barriers to collecting and analyzing high quality family health history Patient barriers to collecting and analyzing high quality family health history System barriers to collecting and analyzing high quality family health history Technology to overcome existing barriers to collection and analysis The ideal family health history platform Impact on clinical care Patient’s ability and willingness to enter family health history information into a digital health risk assessment tool Provider’s perceptions of risk assessment technology and its impact on their clinical care Does systematic risk assessment using digital health technology enhance the quality of clinical care Summary References Family health history and genetic counseling What is a genetic counselor? Using family health history as a psychosocial instrument Autonomous decision making about genetic testing How genetic counselors can help providers Who should be tested? Which test to choose? Facilitating patient understanding How do I refer to or work with a genetic counselor? Challenges of direct-to-consumer genetic testing Expansion of the genetic counseling field New models of genetic counseling Improving patient experiences with genetics Summary and conclusions References Current and future trends in diagnostics and treatment Epigenetics Clear cut environmental triggers have not been identified for most epigenetic processes Epigenetic mechanisms are not “purely” environmental Integrating digital family health history into the EHR and consumer apps Polygenic risk scores Medically relevant single nucleotide polymorphisms (SNPs) have been employed to develop polygenic risk scores for various d ... Expanding the size and scope of polygenic risk scores—Future challenges and risks Polygenic risk scores and family history in clinical care Genome-wide SNP arrays Genomic sequencing References Current and future trends to integrate family health history with clinical programs to improve population health We are all related Healthcare models that promote health through new processes Genetic screening in the population Families can help each other understand genetics and prevent disease References Epilogue Some resources for patients Overview of genes, genetics Importance of family health history and worksheets for collecting it Blood clots that run in families/Thrombophilia Breast cancer Cardiovascular disease Colon cancer Diabetes Familial hypercholesterolemia Ovarian cancer Variants of uncertain significance Some resources for doctors Index A B C D E F G H I J L M N O P R S T V