Genetics in medical practice

Korf, Bruce R.

doi:10.1097/00125817-200211001-00003

Cited by 16 publications

(9 citation statements)

References 17 publications

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“…In fact, after two decades of work, with substantial funding, GWAS have uncovered numerous reproducible associations of common genetic variants, mostly single nucleotide polymorphisms (SNPs; sometimes called “simple nucleotide polymorphisms” to include small insertion or deletion variants), with human traits and diseases. It is true that the cumulative effects of disease-associated SNPs have failed to account for the majority of complex-trait heritability [2], but mature GWAS data for many diseases now typically account for more than 10% of such heritability, and this information is starting to have clinical applications, particularly when combined into polygenic risk scores. For example, while the odds ratio (OR) for a given SNP genotype at a GWAS peak (the “GWAS index SNP”) is often <1.2 and seldom >1.4, meta-analyses of, for example, cancer GWAS have shown that the combined effects of a large number of susceptibility loci may become large enough to be useful for risk prediction and targeted prevention, including the provision of more frequent screening [3–5].…”

Section: Successes From Gwas and Challenges For Post-gwasmentioning

confidence: 99%

Genetic–epigenetic interactions in cis: a major focus in the post-GWAS era

et al. 2017

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Studies on genetic–epigenetic interactions, including the mapping of methylation quantitative trait loci (mQTLs) and haplotype-dependent allele-specific DNA methylation (hap-ASM), have become a major focus in the post-genome-wide-association-study (GWAS) era. Such maps can nominate regulatory sequence variants that underlie GWAS signals for common diseases, ranging from neuropsychiatric disorders to cancers. Conversely, mQTLs need to be filtered out when searching for non-genetic effects in epigenome-wide association studies (EWAS). Sequence variants in CCCTC-binding factor (CTCF) and transcription factor binding sites have been mechanistically linked to mQTLs and hap-ASM. Identifying these sites can point to disease-associated transcriptional pathways, with implications for targeted treatment and prevention.

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Section: Successes From Gwas and Challenges For Post-gwasmentioning

confidence: 99%

Genetic–epigenetic interactions in cis: a major focus in the post-GWAS era

et al. 2017

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“…Physicians of all specialties are increasingly using genomic tools, including whole genome and whole exome sequencing (1–3) and genotyping for risk variants and pharmacogenomics variants (4, 5). These tools often identify incidental or secondary findings that have important implications for disease, but are unrelated to the original purposes of testing.…”

Section: Introductionmentioning

confidence: 99%

Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease

Christensen

Roberts²,

Whitehouse

et al. 2016

Ann Intern Med

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Background Increasing use of genetic testing raises questions about disclosing secondary findings, including pleiotropic information. Objective To determine the safety and behavioral impact of disclosing modest associations between APOE genotype and coronary artery disease (CAD) risk during APOE-based genetic risk assessments for Alzheimer’s disease (AD). Design Randomized, multicenter equivalence clinical trial Setting Four teaching hospitals Participants 257 asymptomatic adults enrolled, 69% with one AD-affected first degree relative Intervention Disclosing AD and CAD genetic risk information (AD+CAD) versus disclosing only AD genetic risk (AD-only) Measurements Co-primary outcomes were Beck Anxiety Index (BAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores at 12 months. Secondary outcomes included test-related distress at 12 months, all measures at 6 weeks and 6 months, and health behavior changes at 12 months. Results 12 months after disclosure, mean BAI scores were 3.5 and 3.5 in AD-only and AD+CAD arms (Δ=0.0, 95%CI: −1.0 to 1.0), and mean CES-D scores were 6.4 and 7.1 in AD-only and AD+CAD arms (Δ=0.7, 95%CI: −1.0 to 2.4). Both confidence bounds fell within the equivalence margin of +/−5 points. Among ε4-positive participants, distress was lower in AD+CAD arms than AD-only arms (Δ=−4.8, 95%CI: −8.6 to −1.0) (p=0.031 for disclosure arm x APOE genotype). AD+CAD participants also reported more health behavior changes, regardless of APOE genotype. Limitations Outcomes were self-reported from volunteers without severe anxiety, severe depression, or cognitive problems. Analyses omitted 33 randomized participants. Conclusion Disclosing pleiotropic information did not increase anxiety or depression, and may have decreased distress among those at increased risk for two conditions. Providing risk modification information regarding CAD improved health behaviors. Findings highlight potential benefits of secondary genetic findings disclosure when options exist for decreasing risk.

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“…Changes are already occurring in the provision of genetic services and the redefinition of professional roles [4,5,6,7,8], with a strong tendency to favour the integration of genetic medicine into other specialties [9] and into primary care [10,11,12,13,14,15]. In fact, the UK [16], many states in the USA [17,18], and some Canadian provinces such as Ontario [19] and Quebec [20] have developed plans for restructuring their genetic services.…”

Section: Introductionmentioning

confidence: 99%

Genetics in Health Care: An Overview of Current and Emerging Models

Battista

Blancquaert

Laberge

et al. 2011

Public Health Genomics

109

106

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Background: With advances in genetic and genomic medicine, the optimal integration of genetic services into the health care system remains of major concern in many countries. Objectives: To review the current organisation of genetic services, mostly in Europe, North America and Australia, explore emerging service delivery models, and probe challenges inherent in the transition process. Methods: We conducted a literature review of genetics in clinical practice: testing, diagnosis, counselling, and treatment. We examined the basic structures of genetic services, examples of integrated networks, and existing professional resources. We investigated services belonging traditionally in medical genetics as well as those developed for more common diseases. Results: Multidisciplinary specialist clinics and coordinated services appeared to be key to delivering proper care in rare genetic disorders. For oncogenetics, neurogenetics and cardiogenetics, interprofessional collaboration between geneticists and other specialists seemed to be favoured. On the other hand, there was also a tendency toward the integration of genetic services directly into primary care. Among the most pressing challenges was the morphing of paediatric care into adult care. Conclusion: The coordination of activities between professionals in first-, second-, and third-line medical care is a primary objective calling for the reconfiguration of professional roles and responsibilities. This entails the forging of new relationships as well as an enhanced sharing of expertise and genetic information, including information regarding services. Barriers to overcome include the redistribution of roles, sharing of data and databases, and the lack of preparedness of non-genetics professionals and of the health care system in general.

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Genetics in medical practice

Cited by 16 publications

References 17 publications

Genetic–epigenetic interactions in cis: a major focus in the post-GWAS era

Genetic–epigenetic interactions in cis: a major focus in the post-GWAS era

Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease

Genetics in Health Care: An Overview of Current and Emerging Models

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