Genomewide linkage analysis of weight change in the Framingham Heart Study

Background: Weight gain adversely affects blood pressure, lipids, and glycemia. The genetic contribution to weight change is unknown. Methods: Variance components linkage analysis using microsatellites was performed on 336 families from the Framingham Heart Study offspring cohort, using a 10-cM genome-wide linkage analysis. We evaluated linkage to two traits: short-term (8-yr) weight change and long-term ( up to 24-yr) weight change. Models were adjusted for age, age squared, baseline weight, smoking status, and menopausal status. Results: Mean short-term weight change ranged from 1.4 - 3.8 kg, and mean long-term weight change was 7.7 kg. The heritability of long-term weight change was 0.24; weight change was minimally heritable among younger individuals and over shorter follow-up intervals. We found significant evidence for linkage for long-term weight change, with a peak LOD score of 3.10 on chromosome 20 at 63.7 cM ( nearest marker, D20S481). We also found suggestive evidence for linkage on chromosome 1 at 239.7 cM ( LOD score, 2.28; nearest marker, D1S1644). Conclusion: Long-term weight change is heritable, and evidence for linkage exists on chromosomes 1 and 20. Potential candidate genes include MC3R, ASIP, AGT, and HSD11B1. Additional research is necessary to uncover the genetic underpinnings of weight change that might contribute to associated adverse metabolic profiles.