Low copy number of the salivary amylase gene predisposes to obesity

• Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. 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. © 2014 Nature America, Inc. All rights reserved.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

alpha amylase pancreas isoenzyme

alpha amylase saliva isoenzyme

adult

article

body mass

carbohydrate metabolism

controlled study

copy number variation

enzyme blood level

fat mass

female

gene cluster

gene expression

gene identification

genetic association

genetic predisposition

genetic variability

heritability

human

human tissue

insulin release

major clinical study

male

nucleotide sequence

obesity

priority journal

saliva level

subcutaneous fat

adipose tissue

Chinese

enzyme activity

European

gene linkage disequilibrium

gene mapping

gene replication

genetic risk

overlapping gene

principal component analysis

sugar intake

Body Mass Index

Gene Dosage

Genetic Predisposition to Disease

Genomics

Humans

Microarray Analysis

Odds Ratio

Salivary alpha-Amylases

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