Measuring missing heritability: Inferring the contribution of common variants
Abstract
Studies have identified thousands of common genetic variants associated with hundreds of diseases. Yet, these common variants typically account for a minority of the heritability, a problem known as "missing heritability." Geneticists recently proposed indirect methods for estimating the total heritability attributable to common variants, including those whose effects are too small to allow identification in current studies. Here, we show that these methods seriously underestimate the true heritability when applied to case-control studies of disease. We describe a method that provides unbiased estimates. Applying it to six diseases, we estimate that common variants explain an average of 60% of the heritability for these diseases. The framework also may be applied to case-control studies, extreme-phenotype studies, and other settings.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- December 2014
- DOI:
- 10.1073/pnas.1419064111
- Bibcode:
- 2014PNAS..111E5272G