[Toward a more rational field-genetic epidemiology]

Area of Science:

• Genetics
• Medical Genetics
• Human Genetics

Context:

• Positional cloning is a key method for isolating disease-related genes.
• Conventional methods include family-based and case-control studies.
• Japanese cultural practices facilitate long-term genetic linkage analysis.

Purpose:

• To review family-based studies on single-gene and multifactorial diseases.
• To discuss theoretical aspects of odds ratio, phenocopy rate, and penetrance.
• To propose an optimized two-stage study design for genetic research.

Summary:

• Presents family-based studies on Akita diabetic mice, systemic carnitine deficiency, Hartnup disease, intracranial aneurysm, moyamoya, and arteriovenous malformation.
• Analyzes a dominant association model, predicting that high odds ratios facilitate familial clustering.
• Suggests genetic markers with odds ratio >/= 8 for clinical screening.

Impact:

• Proposes a rational two-stage study design: linkage analysis (family study) followed by case-control association study replication.
• This design is more efficient than two independent case-control studies.
• Expected to identify high-odds-ratio polymorphisms with minimal research budgets.