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A major predisposition locus for severe obesity, at 4p15-p14
Authors:Stone Steven  Abkevich Victor  Hunt Steven C  Gutin Alexander  Russell Deanna L  Neff Chris D  Riley Robyn  Frech Georges C  Hensel Charles H  Jammulapati Srikanth  Potter Jennifer  Sexton David  Tran Thanh  Gibbs Drew  Iliev Diana  Gress Richard  Bloomquist Brian  Amatruda John  Rae Peter M M  Adams Ted D  Skolnick Mark H  Shattuck Donna
Institution:Myriad Genetics, Inc., 320 Wakara Way, Salt Lake City, UT 84108, USA. sstone@myriad.com
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.
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