FNIP1 variants are associated with favourable metabolism in 1 million humans.

Rare protein-truncating variants in FNIP1 are linked to a 60% reduction in cardiometabolic disease risk in over one million humans.

• Why it matters: Understanding genetic influences on energy metabolism can reveal targets for preventing or treating cardiometabolic diseases, which are leading causes of death worldwide.
• What they did: The study analyzed exome sequences from 1,032,116 individuals across multiple continents, identifying 59 genes related to energy balance, including rare FNIP1 variants associated with favorable metabolic traits.
• The result: FNIP1 variants correlate with lower triglyceride-to-HDL ratios, reduced liver fat, improved insulin sensitivity, and decreased disease odds, suggesting FNIP1 inhibition as a promising therapeutic approach.