A major predisposition locus for severe obesity, at 4p15-p14.
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.
Stone
Steven
S
Myriad Genetics, Inc., 320 Wakara Way, Salt Lake City, UT 84108, USA. sstone@myriad.com
Abkevich
Victor
V
Hunt
Steven C
SC
Gutin
Alexander
A
Russell
Deanna L
DL
Neff
Chris D
CD
Riley
Robyn
R
Frech
Georges C
GC
Hensel
Charles H
CH
Jammulapati
Srikanth
S
Potter
Jennifer
J
Sexton
David
D
Tran
Thanh
T
Gibbs
Drew
D
Iliev
Diana
D
Gress
Richard
R
Bloomquist
Brian
B
Amatruda
John
J
Rae
Peter M M
PM
Adams
Ted D
TD
Skolnick
Mark H
MH
Shattuck
Donna
D
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
D005819:Genetic Markers