In this study, we attempted for the first time to identify small-effect QTL in an F2 progeny. Small-effect QTL are defined as those reaching the threshold value of P = 0.05 but that did not reach the significant threshold value suggested by Lander and Botstein [26]. Although not significant, there is evidence that most of the eight small-effect QTL likely contain susceptibility genes for CIA. First, we performed the linkage analysis in three datasets, including all 290 F progeny, 76 C5+/+ F2 progeny and 133 C5+/- F2 progeny. Five of the eight small-effect QTL were identified in at least two datasets, suggesting that these QTL are reproducible. Second, many QTL identified in the present study overlap with arthritis QTL previously identified, including loci 1, 2, 5 and 6. In addition, syntenic analysis revealed that the counterpart genomic regions on the human genome of many of these eight QTL are linked to RA.