Challenges in the phenotypic characterisation of patients in genetic studies of coronary artery disease

Luo, Albert; Jefferson, Brian; García, Mario J.; Ginsburg, Geoffrey S.; Topol, Eric J.

doi:10.1136/jmg.2006.045732

Cited by 25 publications

(26 citation statements)

References 43 publications

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“…We found few studies investigating the validity of diagnosis among different AMI phenotypes, with most focusing on composite AMI despite emerging data suggesting important differences in survival and outcomes among those with different AMI phenotypes [38]. Association studies using "omic" technology will benefit from greater phenotyping of AMI in order to derive mechanistic insights [11,39,40].…”

Section: Discussionmentioning

confidence: 98%

Use of electronic health records to ascertain, validate and phenotype acute myocardial infarction: A systematic review and recommendations

Rubbo

Fitzpatrick

Denaxas

et al. 2015

International Journal of Cardiology

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Electronic health records (EHRs) offer the opportunity to ascertain clinical outcomes at large scale and low cost, thus facilitating cohort studies, quality of care research and clinical trials. For acute myocardial infarction (AMI) the extent to which different EHR sources are accessible and accurate remains uncertain. Using MEDLINE and EMBASE we identified thirty three studies, reporting a total of 128658 patients, published between January 2000 and July 2014 that permitted assessment of the validity of AMI diagnosis drawn from EHR sources against a reference such as manual chart review. In contrast to clinical practice, only one study used EHR-derived markers of myocardial necrosis to identify possible AMI cases, none used electrocardiogram findings and one used symptoms in the form of free text combined with coded diagnosis. The remaining studies relied mostly on coded diagnosis. Thirty one studies reported positive predictive value (PPV)≥ 70% between AMI diagnosis from both secondary care and primary care EHRs and the reference. Among fifteen studies reporting EHR-derived AMI phenotypes, three cross-referenced ST-segment elevation AMI diagnosis (PPV range 71-100%), two non-ST-segment elevation AMI (PPV 91.0, 92.1%), three non-fatal AMI (PPV range 82-92.2%) and six fatal AMI (PPV range 64-91.7%). Clinical coding of EHR-derived AMI diagnosis in primary care and secondary care was found to be accurate in different clinical settings and for different phenotypes. However, markers of myocardial necrosis, ECG and symptoms, the cornerstones of a clinical diagnosis, are underutilised and remain a challenge to retrieve from EHRs.

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Section: Discussionmentioning

confidence: 98%

Use of electronic health records to ascertain, validate and phenotype acute myocardial infarction: A systematic review and recommendations

Rubbo

Fitzpatrick

Denaxas

et al. 2015

International Journal of Cardiology

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“…A significant source of difficulty has been from poor phenotypic characterization of cases and control subjects (74). Unlike AMD and type 2 DM where a well-accepted phenotype and a standard definition of disease exist, atherosclerotic CAD has a wide range of clinical manifestations, from asymptomatic disease to acute MI to sudden cardiac death.…”

Section: Challenges To Progressmentioning

confidence: 99%

Future Use of Genomics in Coronary Artery Disease

Damani

Topol

2007

Journal of the American College of Cardiology

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Coronary artery disease (CAD) remains the number one cause of death in industrialized countries despite our collective efforts to minimize attributable risk from known contributors to CAD such as hypertension, dyslipidemia, and smoking. In addition, clinical trials have consistently demonstrated a family history of coronary disease to be predictive for future cardiovascular events beyond that which would be explained by traditional risk factors. These findings support and have prompted widespread investigation into the genomic basis of CAD and myocardial infarction (MI). Recent advances in genotyping technology have allowed for easier identification and confirmation of susceptibility genes for complex traits across different cohorts via increased power of studies stemming from faster accrual of cases and control subjects and more precise genetic mapping. These technological advances have resulted in defining the genes contributing to a substantial or even majority of population-attributable risk for type 2 diabetes and age-related macular degeneration (AMD) cases. Similar progress in replicating novel susceptibility genes for CAD and specifically MI is now rapidly occurring, with a recent gene marker on chromosome 9p21 representing a highly significant and common variant susceptibility factor. With improved resequencing technology and better phenotypic characterization of our CAD cases and control subjects, we should achieve successes in gene identification and confirmation similar to diabetes and AMD, thereby allowing us to better quantify CAD risk earlier in life and institute more effective therapy reducing the individual propensity to develop CAD.

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“…Human genetic studies depend on precise and accurate phenotyping. Investigators appreciate that anything less, particularly in control groups, imposes major limitations in data analysis [37]. Despite thoroughly evaluating presumably normal participants, there are some factors that cannot be controlled.…”

Section: Using the Genetic Family History In Research The Working Genmentioning

confidence: 99%

The Family History: Reemergence of an Established Tool

Hinton

2008

Critical Care Nursing Clinics of North America

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Challenges in the phenotypic characterisation of patients in genetic studies of coronary artery disease

Cited by 25 publications

References 43 publications

Use of electronic health records to ascertain, validate and phenotype acute myocardial infarction: A systematic review and recommendations

Use of electronic health records to ascertain, validate and phenotype acute myocardial infarction: A systematic review and recommendations

Future Use of Genomics in Coronary Artery Disease

The Family History: Reemergence of an Established Tool

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