We have previously used this same sequencing approach in affected cousins belonging to high-risk pedigrees to identify multiple candidate predisposition variants for several different phenotypes, including GOLM1 for melanoma [38], ERF for bladder cancer [36], FANCM for colorectal cancer [39], MEGF for osteoporosis [40], HOXC4 for Chiari Malformations [41], and multiple candidates for Alzheimer’s [42] and exceptional longevity [43], among others. The gene discussed is HOXC4; the disease is osteoporosis.