To better understand their functional consequences, we evaluated the 69 novel genes in the Hybrid Mouse Diversity Panel (HMDP) for correlation with multiple obesity-related traits. This panel includes 100 inbred mice strains with extensive collection of obesity-related phenotypes from ~12,000 genes. Of the 69 novel TWAS genes previously identified, 40 were present in the panel and could be evaluated for effect on phenotype. Of these, 26 were significantly associated with at least one obesity-related trait (after accounting for genes tested) and 14 remained significant after accounting for 36 phenotypes tested (very conservatively assuming the phenotypes were independent) (Supplementary Table 14). 77% of the genes with an association were associated with multiple phenotypes. For example, expression of Ftsj3 was significantly correlated with fat mass, glucose-to-insulin ratio, and body weight in both liver and adipose tissue, with R2 ranging from 0.20–0.28. Another candidate, Iih4, was significantly correlated with LDL and TC levels in liver. In humans, this gene is also linked to hypercholesterolemia in OMIM and was previously associated with BMI in East Asians41. Due to complex correlation of phenotypes, it is
