title: A major predisposition locus for severe obesity, at 4p15-p14.
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.
authors.affiliation: Myriad Genetics, Inc., 320 Wakara Way, Salt Lake City, UT 84108, USA. sstone@myriad.com
authors.forename: Steven
authors.initials: S
authors.lastname: Stone
authors.forename: Victor
authors.initials: V
authors.lastname: Abkevich
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
authors.forename: Alexander
authors.initials: A
authors.lastname: Gutin
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Russell
authors.forename: Chris D
authors.initials: CD
authors.lastname: Neff
authors.forename: Robyn
authors.initials: R
authors.lastname: Riley
authors.forename: Georges C
authors.initials: GC
authors.lastname: Frech
authors.forename: Charles H
authors.initials: CH
authors.lastname: Hensel
authors.forename: Srikanth
authors.initials: S
authors.lastname: Jammulapati
authors.forename: Jennifer
authors.initials: J
authors.lastname: Potter
authors.forename: David
authors.initials: D
authors.lastname: Sexton
authors.forename: Thanh
authors.initials: T
authors.lastname: Tran
authors.forename: Drew
authors.initials: D
authors.lastname: Gibbs
authors.forename: Diana
authors.initials: D
authors.lastname: Iliev
authors.forename: Richard
authors.initials: R
authors.lastname: Gress
authors.forename: Brian
authors.initials: B
authors.lastname: Bloomquist
authors.forename: John
authors.initials: J
authors.lastname: Amatruda
authors.forename: Peter M M
authors.initials: PM
authors.lastname: Rae
authors.forename: Ted D
authors.initials: TD
authors.lastname: Adams
authors.forename: Mark H
authors.initials: MH
authors.lastname: Skolnick
authors.forename: Donna
authors.initials: D
authors.lastname: Shattuck
mesh_terms: D015992:Body Mass Index; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D009765:Obesity / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012727:Sex Characteristics; D014589:Utah
chemical_list: D005819:Genetic Markers