Evidence of a Novel Quantitative-Trait Locus for Obesity on Chromosome 4p in Mexican Americans

Rector Arya, Ravindranath Duggirala, Christopher P. Jenkinson, Laura Almasy, John Blangero, Peter O'Connell, Michael P. Stern

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Although several genomewide scans have identified quantitative-trait loci influencing several obesity-related traits in humans, genes influencing normal variation in obesity phenotypes have not yet been identified. We therefore performed a genome scan of body mass index (BMI) on Mexican Americans, a population prone to obesity and diabetes, using a variance-components linkage analysis to identify loci that influence BMI. We used phenotypic data from 430 individuals (26% diabetics, 59% females, mean age ± SD = 43 ± 17 years, mean BMI ± SD = 30.0 ± 6.7, mean leptin (ng/ml) ± SD = 22.1 ± 17.1) distributed across 27 low-income Mexican American pedigrees who participated in the San Antonio Family Diabetes Study (SAFDS) for whom a 10-15-cM map is available. In this genomewide search, after accounting for the covariate effects of age, sex, diabetes, and leptin, we identified a genetic region exhibiting the most highly significant evidence for linkage (LOD 4.5) with BMI on chromosome 4p (4p15.1) at 42 cM, near marker D4S2912. This linkage result has been confirmed in an independent linkage study of severe obesity in Utah pedigrees. Two strong positional candidates, the human peroxisome proliferator-activated receptor gamma coactivator 1 (PPARGC1) and cholecystokinin A receptor (CCKAR) with major roles in the development of obesity, are located in this region. In conclusion, we identified a major genetic locus influencing BMI on chromosome 4p in Mexican Americans.

Original languageEnglish (US)
Pages (from-to)272-282
Number of pages11
JournalAmerican Journal of Human Genetics
Volume74
Issue number2
DOIs
StatePublished - Feb 2004

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Evidence of a Novel Quantitative-Trait Locus for Obesity on Chromosome 4p in Mexican Americans'. Together they form a unique fingerprint.

  • Cite this