TY - JOUR
T1 - Evidence of a Novel Quantitative-Trait Locus for Obesity on Chromosome 4p in Mexican Americans
AU - Arya, Rector
AU - Duggirala, Ravindranath
AU - Jenkinson, Christopher P.
AU - Almasy, Laura
AU - Blangero, John
AU - O'Connell, Peter
AU - Stern, Michael P.
N1 - Funding Information:
This research was supported in part by grants from National Institutes of Health (DK42273, DK47482, DK53889, and MH59490). R.A., the William K. Warren Diabetes Fellow of the ADA Mentor-Based Postdoctoral Fellowship, was supported by the William K. Warren Medical Research Institute. We wish to thank the participants of the SAFDS families for their support and cooperation. We also wish to thank S. Fowler, K. Williams, R. Granato, and T. D. Dyer for their help and support.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2004/2
Y1 - 2004/2
N2 - 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.
AB - 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.
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U2 - 10.1086/381717
DO - 10.1086/381717
M3 - Article
C2 - 14740316
AN - SCOPUS:0842264056
VL - 74
SP - 272
EP - 282
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 2
ER -