Quantitative trait loci for insulin-like growth factor I, leptin, thyroxine, and corticosterone in genetically heterogeneous mice

Genotype information was collected at 87 loci in a group of 1,108 UM-HET3 mice bred as the progeny of [BALB/cJ × C57BL/6J]F1 mothers and [C3H/HeJ × DBA/2J]F1 fathers, for which thyroxine (T4), insulin-like growth factor I (IGF-I), and leptin levels had been measured at 4 and 15 mo of age. The data provided significant evidence for quantitative trait loci (QTL) modulating IGF-I levels on chromosomes 1, 3, 8, 10, and 17; for loci affecting T4 on chromosomes 4, 15, and 17; and for leptin on chromosome 3. Fecal levels of corticosterone at 17 mo of age were influenced by a QTL on chromosome 1. Nine other gene/hormone associations reached a nominal P < 0.01, providing suggestive but not statistical evidence for additional QTL. QTL with an influence on a given hormone were in nearly all cases additive, with little or no evidence for epistasis. Of the 12 strongest QTL, 5 had effects that were age dependent, having more effect in 15-mo-old than in 4-mo-old mice in all but one case; the other QTL had effects that were apparently age-independent. These results show that the genetic controls over late-life hormone levels are complex and dependent on effects of genes that act both early and late in the life course.