Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes
Abstract
Genome sequencing of individuals in the population reveals new mutations in almost every protein coding gene; interpreting the consequence of these mutations for human health and disease remains challenging. We sequenced the gene PPARG, a target of antidiabetic drugs, in nearly 20,000 individuals with and without type 2 diabetes (T2D). We identified 49 previously unidentified protein-altering mutations, characterized their cellular function in human cells, and discovered that nine of these mutations cause loss-of-function (LOF). The individuals who carry these nine LOF mutations have a sevenfold increased risk of T2D, whereas individuals carrying mutations we classify as benign have no increased risk of T2D.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- September 2014
- DOI:
- 10.1073/pnas.1410428111
- Bibcode:
- 2014PNAS..11113127M