Nutr Res Pract.  2016 Feb;10(1):115-124. 10.4162/nrp.2016.10.1.115.

Genome-wide association study for the interaction between BMR and BMI in obese Korean women including overweight

• Lee M
• Kwon DY
• Kim MS
• Choi CR
• Park MY
• Kim AJ

• KMID: 2313908
• DOI: http://doi.org/10.4162/nrp.2016.10.1.115

Abstract

BACKGROUND/OBJECTIVES
This is the first study to identify common genetic factors associated with the basal metabolic rate (BMR) and body mass index (BMI) in obese Korean women including overweight. This will be a basic study for future research of obese gene-BMR interaction.
SUBJECTS/METHODS
The experimental design was 2 by 2 with variables of BMR and BMI. A genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) was conducted in the overweight and obesity (BMI > 23 kg/m2) compared to the normality, and in women with low BMR (< 1426.3 kcal/day) compared to high BMR. A total of 140 SNPs reached formal genome-wide statistical significance in this study (P < 1 x 10(-4)). Surveys to estimate energy intake using 24-h recall method for three days and questionnaires for family history, a medical examination, and physical activities were conducted.
RESULTS
We found that two NRG3 gene SNPs in the 10q23.1 chromosomal region were highly associated with BMR (rs10786764; P = 8.0 x 10(-7), rs1040675; 2.3 x 10(-6)) and BMI (rs10786764; P = 2.5 x 10(-5), rs10786764; 6.57 x 10(-5)). The other genes related to BMI (HSD52, TMA16, MARCH1, NRG1, NRXN3, and STK4) yielded P <10 x 10-4. Five new loci associated with BMR and BMI, including NRG3, OR8U8, BCL2L2-PABPN1, PABPN1, and SLC22A17 were identified in obese Korean women (P < 1 x 10(-4)). In the questionnaire investigation, significant differences were found in the number of starvation periods per week, family history of stomach cancer, coffee intake, and trial of weight control in each group.
CONCLUSION
We discovered several common BMR- and BMI-related genes using GWAS. Although most of these newly established loci were not previously associated with obesity, they may provide new insights into body weight regulation. Our findings of five common genes associated with BMR and BMI in Koreans will serve as a reference for replication and validation of future studies on the metabolic rate.

Keyword

GWAS; BMR; BMI; obesity

MeSH Terms

Basal Metabolism
Body Mass Index
Body Weight
Coffee
Energy Intake
Female
Genome-Wide Association Study*
Humans
Motor Activity
Obesity
Overweight*
Polymorphism, Single Nucleotide
Research Design
Starvation
Stomach Neoplasms
Coffee

Figure

• 

  Fig. 1 The Manhattan plot for the genome-wide association study (GWAS) of obesity in the Korean female subjects. This plot is based on -log10 (P-value) from GWAS and imputation analysis against chromosome position; each color represents a different chromosome. Blue horizontal line indicates the suggestive association threshold, P = 1 × 10-4. (A) BMR and (B) BMI in these study subjects.

• 

  Fig. 2 Linkage Disequilibrium Plot figure of NRG3 gene SNPs (rs10786764 and rs1040675), black arrow on chromosome 10, in obese Korean women including overweight. The darker red in each diamond shape, stronger LD in association with BMR (A) and BMI (B).

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