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This version published online on March 15, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-1752
A more recent version of this article appeared on June 1, 2005
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Submitted on September 7, 2004
Accepted on March 7, 2005

Genomewide Linkage Analysis of Weight Change in the Framingham Heart Study

Caroline S. Fox*, Nancy L. Heard-Costa, Ramachandran S. Vasan, Joanne M. Murabito, Ralph B. D'Agostino Sr., and Larry D. Atwood

National Heart, Lung, and Blood Institute's Framingham Heart Study (all), the National Heart, Lung, and Blood Institute (CSF), Bethesda, MD; the Department of Endocrinology, Hypertension, and Diabetes, the Brigham and Women's Hospital and Harvard Medical School, Boston MA (CSF); the Departments of Neurology, Boston University School of Medicine (NLH-C and LDA) and Division of General Internal Medicine (JMM), Boston, MA; the Division of Cardiology, Boston University School of Medicine (RSV), Boston, MA; the Department of Mathematics and Statistics (RBD), Boston, MA

* To whom correspondence should be addressed. E-mail: foxca{at}nhlbi.nih.gov.

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-year) weight change, and long-term (up to 24-years) weight change. Models were adjusted for age, age-squared, baseline weight, smoking status, and menopausal status.

Results Mean short-term weight change ranged from 3.1-3.8 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. Further research is necessary to uncover the genetic underpinnings of weight change that might contribute to associated adverse metabolic profiles.
Key words: weight change • linkage • genetic • Framingham Heart Study






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