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A major predisposition locus for severe obesity, at 4p15-p14
Steven Stone1, Victor Abkevich, Steven C Hunt
1Myriad Genetics, Inc., 320 Wakara Way, Salt Lake City, UT 84108, USA. sstone@myriad.com
American Journal of Human Genetics
|April 17, 2002
Summary
Researchers identified a significant gene linkage associated with high body-mass index in females. This finding may explain a substantial portion of the genetic predisposition to severe obesity in women, warranting further investigation.
Area of Science:
- Genetics
- Obesity Research
- Human Genomics
Background:
- The genetic basis of morbid obesity is not fully understood, despite its heritable nature.
- Identifying specific genes linked to obesity predisposition is crucial for understanding disease mechanisms.
Purpose of the Study:
- To conduct a genomewide search for genes contributing to obesity predisposition.
- To identify specific genetic loci linked to high body-mass index (BMI) in multigenerational pedigrees.
Main Methods:
- Utilized a genomewide search with 628 markers across multigenerational Utah pedigrees.
- Performed linkage analysis, including multipoint heterogeneity LOD (HLOD) and nonparametric linkage (NPL) scoring.
- Increased marker density and pedigree size to refine linkage findings.
Main Results:
- Identified a significant linkage on chromosome 4 (D4S2632) for high BMI in females (HLOD 6.1, NPL 5.3).
- Further analysis refined the linkage region (D4S3350) with increased scores (HLOD 9.2, NPL 11.3).
- Linkage supported by nearly half of the analyzed families, suggesting a substantial genetic contribution.
Conclusions:
- A specific gene region on chromosome 4 is strongly linked to high BMI in females.
- This identified gene may account for a significant percentage of genetic predisposition to severe obesity in women.
- Further research is needed to determine the gene's effect in males and the general population.