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Variants in the LEPR gene are nominally associated with higher BMI and lower 24-h energy expenditure in Pima Indians.
- Source :
-
Obesity (Silver Spring, Md.) [Obesity (Silver Spring)] 2012 Dec; Vol. 20 (12), pp. 2426-30. Date of Electronic Publication: 2012 Jun 22. - Publication Year :
- 2012
-
Abstract
- Genome-wide association studies (GWASs) have been used to search for susceptibility genes for type 2 diabetes and obesity in the Pima Indians, a population with a high prevalence of both diseases. In these studies, a variant (rs2025804) in the LEPR gene was nominally associated with BMI in 1,082 subjects (P = 0.03 adjusted for age, sex, birth year, and family membership). Therefore the LEPR and leptin overlapping transcript (LEPROT) genes were selected for further sequencing and genotyping in larger population-based samples for association analyses with obesity-related phenotypes. Selected variants (n = 80) spanning these genes were genotyped in a sample of full-heritage Pima Indians (n = 2,842) and several common variants including rs2025804 were nominally associated with BMI (P = 0.05-0.003 adjusted for age, sex, birth year, and family membership). Four common tag variants associated with BMI in the full-heritage Pima Indian sample were genotyped in a second sample of mixed-heritage Native Americans (n = 2,969) and three of the variants showed nominal replication (P = 0.03-0.006 adjusted as above and additionally for Indian heritage). Combining both samples provided the strongest evidence for association (adjusted P = 0.0003-0.0001). A subset of these individuals (n = 403) had been metabolically characterized for predictors of obesity and the BMI risk alleles for the variants tagged by rs2025804 were also associated with lower 24-h energy expenditure (24hEE) as assessed in a human respiratory chamber (P = 0.0007 adjusted for age, sex, fat mass, fat-free mass, activity, and family membership). We conclude that common noncoding variation in the LEPR gene is associated with higher BMI and lower energy expenditure in Native Americans.
- Subjects :
- Diabetes Mellitus, Type 2 epidemiology
Diabetes Mellitus, Type 2 metabolism
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Male
Obesity epidemiology
Obesity metabolism
Phenotype
Polymorphism, Single Nucleotide
Postprandial Period
Receptors, Leptin metabolism
Thermogenesis
Body Mass Index
Diabetes Mellitus, Type 2 genetics
Energy Metabolism genetics
Indians, North American genetics
Obesity genetics
Receptors, Leptin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1930-739X
- Volume :
- 20
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Obesity (Silver Spring, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 22810975
- Full Text :
- https://doi.org/10.1038/oby.2012.159