Genome-Wide Linkage to Chromosome 6 for Waist Circumference in the Framingham Heart Study

  1. Caroline S. Fox123,
  2. Nancy L. Heard-Costa14,
  3. Peter W.F. Wilson15,
  4. Daniel Levy125,
  5. Ralph B. D’Agostino, Sr.16 and
  6. Larry D. Atwood17
  1. 1National Heart, Lung, and Blood Institute’s Framingham Heart Study, Bethesda, Maryland
  2. 2National Heart, Lung, and Blood Institute, Bethesda, Maryland
  3. 3Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  4. 4Department of Neurology, Boston University School of Medicine, Boston, Massachusetts
  5. 5Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
  6. 6Boston University Statistics and Consulting Unit, Boston, Massachusetts
  7. 7Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
  1. Address correspondence and reprint requests to Caroline S. Fox, MD, MPH, 73 Mt. Wayte Ave., Suite #2, Framingham, MA 01702. E-mail: foxca{at}


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.


    • Accepted January 30, 2004.
    • Received November 26, 2003.
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