External apical root resorption (EARR) is a common orthodontic treatment sequela. Previous studies implicate a substantial genetic component for EARR. Using a candidate gene approach, we investigated possible linkage of EARR associated with orthodontic treatment with the TNSALP, TNFalpha, and TNFRSF11A gene loci. The sample was comprised of 38 American Caucasian families with a total of 79 siblings who completed comprehensive orthodontic treatment. EARR was assessed by means of pre- and post-treatment radiographs. Buccal swab cells were collected for extraction and analysis of DNA. No evidence of linkage was found with EARR and the TNFalpha and TNSALP genes. Non-parametric sibling pair linkage analysis identified evidence of linkage (LOD = 2.5; p = 0.02) of EARR affecting the maxillary central incisor with the microsatellite marker D18S64 (tightly linked to TNFRSF11A). This indicates that the TNFRSF11A locus, or another tightly linked gene, is associated with EARR.