Quantitative trait loci for periosteal circumference (PC): identification of single loci and epistatic effects in F2 MRL/SJL mice

To test the hypothesis that periosteal circumference (PC), which is associated with bone size through cross-sectional moment of inertia (CMI), has heritable components, we performed a linkage analysis using 633 MRL/SJL F2 mice that have 14% difference in mean PC. PC was determined in femurs by use of peripheral quantitative computerized tomography (pQCT). The genome-wide scan identified nine QTL for PC adjusted by body weight on chromosomes 1 (2 QTL), 2 (2 QTL), 8, 11, 15, 17, and X, which accounted for 38.6% of phenotype variance. QTL on chromosomes 1 (D1Mit33), 8 (D8Mit125), 15 (D15Mit 62), 17 (D17Mit176), and X (DXMit208) were unique for PC adjusted by body weight and femur length, while the remaining PC QTL were shared with body weight but not femur length. Four epistatic interactions were identified which accounted for 37.6% of phenotype variance. There was also evidence of pleiotropic effects on chromosome 11 among four size phenotypes (PC, body length, body weight, bone mineral density, and muscle size), which may represent a common genetic mechanism that may regulate bone size and body size.