Genome-wide association studies may be misinterpreted: genes versus heritability

Area of Science:

• Genetics
• Epidemiology
• Biostatistics

Background:

• Genome-wide association studies (GWAS) aim to identify genetic variants contributing to common diseases.
• Heritability estimates from family studies suggest a significant genetic component for many diseases.
• A discrepancy exists between the low percentage of disease variation explained by GWAS and high heritability estimates.

Purpose of the Study:

• To clarify the misunderstanding between heritability and genetic determination in disease etiology.
• To re-evaluate the interpretation of heritability estimates in the context of common diseases.
• To address the gap between GWAS findings and heritability estimates.

Main Methods:

• Conceptual analysis of heritability and genetic determination.
• Review of literature on genome-wide association studies (GWAS) and family studies.
• Illustrative examples to differentiate variation from causation and heritability from genetic determination.

Main Results:

• Heritability studies do not provide valid estimates for the proportion of disease cases attributable to genetic factors.
• Confusion between variation and causation, and heritability and genetic determination, underlies the observed discrepancies.
• Estimates of heritability cannot be used to infer the proportion of disease cases due to environmental factors.

Conclusions:

• Heritability estimates are frequently misinterpreted and do not equate to genetic determination.
• The current understanding of genetic contributions to common diseases requires re-evaluation based on these conceptual clarifications.
• Rethinking the interpretation of family study data is crucial for accurate genetic epidemiology.