While several loci for BMI have been identified, it is not known whether genes underlie the process of regional fat deposition. We sought to test whether waist circumference, a measure of central adiposity, contains a genetic component. Variance components linkage analysis was performed on 330 families from the Framingham Heart Study original and offspring cohorts, using a 10-cM genome-wide linkage analysis. Overall, 2,086 subjects (51% women), mean age 48 years, were available for analysis. The overall heritability of waist circumference was 0.41. The maximum logarithm of odds (LOD) score in the full dataset was 3.3 on chromosome 6 at marker D6S1009; when subjects were limited to those aged <60 years, the peak LOD score was 3.7 at the same location. Substantial evidence exists for linkage to waist circumference, a measure of central adiposity. Potential candidate genes include ESR1, OPRM1, and NMBR. Further research is necessary to understand the genes involved in central adiposity.