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Low copy number of the salivary amylase gene predisposes to obesity
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Journal Article
Low copy number of the salivary amylase gene predisposes to obesity
2014
Overview
Mario Falchi, Philippe Froguel and colleagues report association of a multi-allelic copy number variant encompassing the salivary amylase gene
AMY1
with body mass index and risk of obesity.
Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts
1
,
2
,
3
,
4
. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (
AMY1
) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased
AMY1
copy number was positively associated with both amylase gene expression (
P
= 2.31 × 10
−14
) and serum enzyme levels (
P
< 2.20 × 10
−16
), whereas reduced
AMY1
copy number was associated with increased BMI (change in BMI per estimated copy = −0.15 (0.02) kg/m
2
;
P
= 6.93 × 10
−10
) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13–1.26;
P
= 1.46 × 10
−10
). The OR value of 1.19 per copy of
AMY1
translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 38/61
/ 38/77
/ 45/22
/ 45/61
/ 45/77
/ adult
/ alpha amylase pancreas isoenzyme
/ alpha amylase saliva isoenzyme
/ Amylases
/ Animal Genetics and Genomics
/ Carbohydrate Metabolism - genetics
/ Chinese
/ DNA
/ European
/ fat mass
/ female
/ Genetic Predisposition to Disease
/ Genetic Predisposition to Disease - genetics
/ Genetics
/ Genomes
/ Genomics
/ Grants
/ human
/ Humans
/ letter
/ male
/ Obesity
/ principal component analysis
/ Saliva
/ Salivary alpha-Amylases - blood
/ Salivary alpha-Amylases - genetics
/ Studies
