A major predisposition locus for severe obesity, at 4p15-p14

Steven Stone, Victor Abkevich, Steven C. Hunt, Alexander Gutin, Deanna L. Russell, Chris D. Neff, Robyn Riley, Georges C. Frech, Charles H. Hensel, Srikanth Jammulapati, Jennifer Potter, David Sexton, Thanh Tran, Drew Gibbs, Diana Iliev, Richard Gress, Brian Bloomquist, John Amatruda, Peter M.M. Rae, Ted D. AdamsMark H. Skolnick, Donna Shattuck

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Abstract

Although the predisposition to morbid obesity is heritable, the identities of the disease-causing genes are largely unknown. Therefore, we have conducted a genomewide search with 628 markers, using multigenerational Utah pedigrees to identify genes involved in predisposition to obesity. In the genomewide search, we identified a highly significant linkage to high body-mass index in female patients, at D4S2632, with a multipoint heterogeneity LOD (HLOD) score of 6.1 and a nonparametric linkage (NPL) score of 5.3. To further delineate the linkage, we increased both the marker density around D4S2632 and the size of our pedigree data set. As a result, the linkage evidence increased to a multipoint HLOD score of 9.2 (at D4S3350) and an NPL score of 11.3. Evidence from almost half of the families in this analysis support this linkage, and therefore the gene in this region might account for a significant percentage of the genetic predisposition to severe obesity in females. However, further studies are necessary to clarify the effect that this gene has in males and in the general population.

Original languageEnglish
Pages (from-to)1459-1468
Number of pages10
JournalAmerican Journal of Human Genetics
Volume70
Issue number6
DOIs
Publication statusPublished - 1 Jan 2002

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Stone, S., Abkevich, V., Hunt, S. C., Gutin, A., Russell, D. L., Neff, C. D., Riley, R., Frech, G. C., Hensel, C. H., Jammulapati, S., Potter, J., Sexton, D., Tran, T., Gibbs, D., Iliev, D., Gress, R., Bloomquist, B., Amatruda, J., Rae, P. M. M., ... Shattuck, D. (2002). A major predisposition locus for severe obesity, at 4p15-p14. American Journal of Human Genetics, 70(6), 1459-1468. https://doi.org/10.1086/340670